Arecent report1 described a chronic, progressive, de-bilitating bone disorder in horses with concurrent pulmonary silicosis in the central and coastal regions of California. Horses were examined because of nonspecific lameness involving 1 or multiple limbs, skeletal deformities, and pathologic fractures of bones of the appendicular skeleton. Affected horses had lordosis and bowing of the scapulae; some horses also had neurologic signs associated with degeneration of the cervical portion of the spine. The diagnosis was made on the basis of radiographic, ultrasonographic, or pathologic findings.
During the same time period, several horses were examined at the University of California Veterinary Teaching Hospital with a similar chronic, nonspecific lameness that, on scintigraphic images, had multiple foci of IRU involving bones of the axial and appendicular skeleton. Subjectively, however, conformational changes similar to those described in the previous report1 were thought to be uncommon, and affected horses were younger and thought to be from geographic regions other than those previously reported. These findings suggested a need to further characterize this bone disorder. The purpose of the study reported here, therefore, was to describe clinical and scintigraphic abnormalities in horses with a bone fragility disorder characterized by multiple sites of IRU involving the axial and appendicular skeleton.
Materials and Methods
Case selection criteria—Medical records of horses examined at the University of California Veterinary Medical Teaching Hospital between June 1980 and June 2006 were reviewed. Horses were eligible for inclusion in the present study if they had multiple sites of IRU on scintigraphic images of the axial and appendicular skeleton and if infectious and neoplastic disorders had been excluded as possible causes.
Medical records review—Information obtained from the medical records of horses included in the study consisted of signalment; history; results of physical and lameness examinations; results of clinicopathologic testing, including results of assays of serum vitamin D concentration and serum parathyroid hormone activity; results of scintigraphic, radiographic, and ultrasonographic imaging; and results of histologic examination of bone biopsy specimens. Serum vitamin D concentration and serum parathyroid hormone activity had been measured with a 2-site immunochemiluminometric assay at a commercial laboratory.a
Review of scintigraphic images—For the present study, scintigraphic images were reviewed by 2 authors (JDCA and SMP) to verify sites of IRU recorded in the medical records. For scintigraphic imaging, horses had been sedated with detomidine hydrochloride (0.01 to 0.03 mg/kg [0.0045 to 0.014 mg/lb], IV) and butorphanol tartrate (0.01 to 0.02 mg/kg [0.0045 to 0.009 mg/lb], IV), and 150 to 165 mCi of technetium Tc 99m medronate was administered. Images were obtained 4 hours later with a rectangular, large-field-of-view gamma camerab with a low-energy, high-resolution, parallelhole collimator mounted on a custom-made, centralcolumn movable gantry. For each image, counts were obtained for 1 minute, up to a maximum of 100,000 counts. If a urinary bladder signal was present on any of the images, furosemide (200 mg, IV) was administered, and additional images were obtained after the horse had urinated. Care was taken to ensure that horses were standing squarely and bearing weight equally on the limbs during image acquisition. Lateral views of the forelimbs, hind limbs, cervical vertebrae, or ribs (ie, from the scapula to the 8th rib and from the 8th to the 18th rib) were obtained. Regions of interest included the region from the foot to the pastern and from the metacarpophalangeal or metatarsophalangeal region to the proximal aspect of the metatarsus or metacarpus. Additional forelimb regions of interest included the region from the antebrachium to the elbow and from the shoulder to the scapula. Additional hind limb regions of interest included the region from the tibia to the stifle joint, the region of the hip joint, and the pelvis; dorsoventral views of the pelvis were obtained in addition to the lateral views. All images had been stored on a dedicated nuclear medicine computer.c
Review of radiographic and ultrasonographic images—In all horses, areas of IRU had been examined radiographically.d In horses in which results of radiography were equivocal, ultrasonography had been performed with a 10- to 14-MHz linear transducer.e
Bronchoalveolar lavage—Bronchoalveolar lavage had been performed as described2 in horses with characteristic signs of respiratory tract disease (ie, high respiratory rate at rest, flaring of the nostrils, and abnormal thoracic auscultation findings) and in horses from the central and coastal regions of California.
Bone biopsy—In select horses, bone biopsy specimens had been obtained from areas of IRU. Specimens were obtained with a 6-mm-diameter Michelle trephine after local infiltration with mepivacaine hydrochloride.
Follow-up information—For the present study, follow-up information was obtained through telephone interviews with owners and trainers of affected horses. Information was solicited on current use and management of the horse, outcome of treatment, perceived comfort of the horse, progression of clinical signs, and long-term outcome.
Results
Sixteen horses met the criteria for inclusion in the study. This included 8 mares and 8 geldings. Horses ranged from 4 to 22 years old at the time of examination (median, 9.9 years), with 11 of the horses being t 10 years old.
Scintigraphic findings—At the time of initial examination, all 16 horses had multiple sites of IRU involving 1 (n = 3) or both (13) scapulae; sites of IRU included the spine, body, and neck of the scapula and the supraglenoid region (Figure 1). Other sites of IRU included the ribs (n = 11), sternebrae (8), and cervical vertebrae (4). Nuclear scintigraphy of the hind end was performed in 10 horses. Sites of IRU were seen predominantly in the pelvic bones, including the sacral tuber (n = 9), ilium (6), ischium (3), and tuber coxae (3). Less frequently affected sites included the mandible (2 of 6 mandibles examined), proximal aspect of the radius (2), metacarpus (2), crus (1), and metatarsus (1).
Scintigraphic images of the left scapula (A), right ribs (B), and pelvis (C; dorsoventral view) of a horse with a bone fragility disorder. Notice the multiple areas of IRU.
Citation: Journal of the American Veterinary Medical Association 232, 11; 10.2460/javma.232.11.1694
Scintigraphic images of the left scapula (A), right ribs (B), and pelvis (C; dorsoventral view) of a horse with a bone fragility disorder. Notice the multiple areas of IRU.
Citation: Journal of the American Veterinary Medical Association 232, 11; 10.2460/javma.232.11.1694
Scintigraphic images of the left scapula (A), right ribs (B), and pelvis (C; dorsoventral view) of a horse with a bone fragility disorder. Notice the multiple areas of IRU.
Citation: Journal of the American Veterinary Medical Association 232, 11; 10.2460/javma.232.11.1694
For 5 of the 16 horses, follow-up scintigrams were available for review, and in 3 of these 5 horses, additional sites of IRU were seen on follow-up scintigrams (time between initial and follow-up scintigrams, 1 month to 2 years). Additional sites of involvement included the cervical vertebrae (n = 2), ribs (2), scapula (1), and sternum (1). In the remaining 2 horses, no changes in affected sites were seen on follow-up scintigrams (time between initial and follow-up scintigrams, 6 weeks and 5 months); however, the hind end was not imaged at the time of follow-up scintigraphy in these 2 horses.
Historical and clinical findings—All horses were examined because of chronic intermittent (n = 10) or acute (ie, ≤ 1 month duration; 6) lameness involving a single (10) or multiple (6) limbs that could not be localized by means of regional anesthesia. Duration of clinical signs in the 10 horses with chronic lameness ranged from 3 to 24 months. Three of the horses with acute lameness were examined because of a sudden onset of severe lameness unrelated to exercise or another obvious inciting cause. The other 3 horses with acute lameness were examined because of a sudden onset of lameness between 4 weeks and 18 months after beginning a rehabilitation program for lameness involving a different limb. For all horses, severity of lameness ranged from grade 2 to 5, on a scale from 0 to 5.3
Other musculoskeletal abnormalities that were identified included atrophy of the shoulder muscles (n = 8), extreme lordosis (3), markedly decreased range of motion of the cervical portion of the spine in the dorsoventral and mediolateral planes (3), moderate to severe lateral bowing of both scapulae (3), and gluteal muscle atrophy (1).
Historically, owners reported that the severity of lameness fluctuated depending on degree or duration of exercise or progressed in severity in conjunction with other musculoskeletal, respiratory tract, and pain-related signs. Deterioration of the clinical condition prior to initial examination was associated with progressive stiffness (n = 6); increased respiratory effort (4); lordosis (3); an acute injury of the affected limb (3); ataxia secondary to cervical osteoarthritis (1); and signs of pain involving the thoracolumbar region, forelimb, and cervical region (1).
Lameness did not improve after diagnostic nerve blocks up to the level of the median and ulnar nerves in 8 horses with unilateral forelimb lameness, nor did it improve after anesthesia of the elbow joint, shoulder joint, and bicipital bursa in 6 of those horses. One horse had a history of some improvement in lameness after anesthesia of the metacarpophalangeal joint.
Seven horses had signs of respiratory tract disease, including a high respiratory rate (n = 4), excessive adventitial lung sounds on auscultation (4), consistent nostril flaring at rest (3), and exercise intolerance (3). Three of 7 horses had confirmed cytologic evidence of pulmonary silicosis.
Weight loss was evident in 3 horses. Body condition score ranged from 4 to 6, on a scale from 1 to 9,4 in 13 horses, but was ≤ 3 in the remaining 3 horses. Other physical parameters, including rectal temperature, pulse rate, mucous membrane color, capillary refill time, and gastrointestinal tract motility, were unremarkable.
Diagnostic imaging findings—In 14 of the 16 horses, radiographs of various sites of IRU had been obtained. Abnormalities were seen in 8 of the 10 horses in which radiographs of the scapula were obtained, all 4 horses in which radiographs of the cervical vertebrae were obtained, 2 of the 6 horses in which radiographs of the mandible were obtained, and 2 of the 10 horses in which radiographs of the ribs were obtained. Specific radiographic abnormalities included fracture of the scapula (n = 4); osteolysis of the mandible, rib, or scapula; and proliferative new bone formation involving the rib, scapula, or multiple cervical vertebrae.
Ultrasonography of the scapula was performed in 11 horses, and abnormalities were identified in 9. The most common abnormality included mild to marked thickening of the scapular spine associated with periosteal surface remodeling (Figure 2), which was seen in 7 of the 14 scapulae that were imaged (in 3 horses, both scapulae were imaged). Other abnormalities that were seen included mild secondary shoulder joint disease (2 horses) and cystic lucency of the scapula (1 horse).
Ultrasonographic images of the left (A) and right (B) scapulae of a horse with a bone fragility disorder. Notice the thickening and remodeling of the right scapular spine.
Citation: Journal of the American Veterinary Medical Association 232, 11; 10.2460/javma.232.11.1694
Ultrasonographic images of the left (A) and right (B) scapulae of a horse with a bone fragility disorder. Notice the thickening and remodeling of the right scapular spine.
Citation: Journal of the American Veterinary Medical Association 232, 11; 10.2460/javma.232.11.1694
Ultrasonographic images of the left (A) and right (B) scapulae of a horse with a bone fragility disorder. Notice the thickening and remodeling of the right scapular spine.
Citation: Journal of the American Veterinary Medical Association 232, 11; 10.2460/javma.232.11.1694
Thoracic radiography was performed in 12 horses, and abnormalities were seen in 8. The most common abnormalities were a diffuse bronchial interstitial pattern (n = 5), a severe bronchointerstitial granulomatous pattern involving the caudal and caudoventral lung fields (2), and hilar lymph node enlargement and a mild to moderate bronchial pattern (1).
Geographic distribution—Six horses were from the Monterey-Carmel Peninsula in the mid coastal region of California, 4 were from Sonoma County in Northern California, 4 were from Napa County, 1 was from the Sacramento Valley, and 1 was from the Silicon Valley south of San Francisco. Horses from the Monterey-Carmel Peninsula, Sonoma County, and Silicon Valley had lived in those areas for 4 to 22 years (median, 6 years). Horses from Napa Valley had lived in the area for 3 to 10 years (median, 10 years). The horse from the Sacramento Valley had lived in the area for 3 years.
Clinicopathologic findings—Results of a CBC performed at the time of initial examination were available for 13 horses. The only abnormalities were mild leukocytosis and neutrophilia in 2 horses. Results of a serum biochemical profile performed at the time of initial examination were available for 11 horses. Abnormalities included high creatine kinase activity (6 horses; range, 300 to 2,520 U/L; reference range, 119 to 287 U/L), high total protein concentration (6 horses; range, 7.8 to 8.5 g/dL; reference range, 5.8 to 7.7 g/dL), high total bilirubin concentration (5 horses; range, 2.4 to 7.1 mg/dL; reference range, 0.5 to 2.3 mg/dL), high alkaline phosphatase activity (1 horse; 354 U/L; reference range, 86 to 285 U/L), high aspartate transaminase activity (2 horses; 540 and 680 U/L; reference range, 168 to 494 U/L), and low total calcium concentration (3 horses; range, 10.2 to 10.6 mg/dL; reference range, 11.4 to 14.1 mg/dL). Serum parathyroid hormone concentration was measured in 7 horses and was slightly high in 3 (range, 2.4 to 7.1 U/L; reference range, 0.5 to 2.0 U/L). Vitamin D concentration was considered normal in the 3 horses in which it was measured (range, 15 to 27 mmol/L; reference range, 15 to 35 mmol/L). Results were normal in all 8 horses in which a urinalysis was performed. Urinary magnesium concentration measured in 7 horses was high in only 1 (68.2 mg/dL; reference range, 1.9 to 3.0 mg/dL).
Bronchoalveolar lavage was performed in 7 horses, and results of cytologic evaluation of lavage fluid were abnormal in 3. High numbers of histiocytes and mineral aggregates characteristic of pulmonary silicosis were identified in all 3 horses.
Histologic findings—Biopsy specimens were obtained from the scapula in 6 horses, from the ribs in 1, and from the scapula and tuber coxae in 1. The most consistent histologic findings were fibrosis and osteopenia (n = 4), focal areas of osteoclastic resorption (1), and severe periosteal proliferation (1). No abnormalities were seen in biopsy specimens from 2 horses.
Treatment—Treatment consisted primarily of rest alone (3 horses) or rest and administration of phenylbutazone (1 g, PO, q 12 h for 10 to 14 days, then as needed; 13 horses). Median duration of stall rest or turn out was 6 months (range, 6 weeks to 18 months). Four horses were also treated with corticosteroids for 7 to 28 days. One horse with signs of pain and stiffness associated with swayback conformation received injections of methylprednisolone acetate (total dose, 200 mg). Other treatments consisted of chiropractic adjustments (4 horses), acupuncture (3 horses), supplements (vitamins, 3 horses; methylsulfonylmethane, 1 horse), gallium nitrate (1 horse), concentrated silicon substitutef (1 horse), and chondroprotective agents (glucosamine, 1 horse; and polysulfated glycosaminoglycans,g 1 horse).
Treatment was associated with transient improvements in clinical signs in 8 horses. The remaining 8 horses did not have any signs of clinical improvement regardless of the treatment administered. In all horses, treatment did not resolve or halt the progression of clinical signs, although 3 horses responded well enough to return to a level of use compatible with owner expectations for a period of time. Five horses had a deterioration as soon as riding was resumed. Two horses that were initially examined because of lameness developed bowing of the scapula and cervical stiffness over the succeeding 2 to 5 years.
Eleven of the 16 horses were euthanized, including 6 that were euthanized immediately after the diagnosis was made. Median survival time for the other 5 horses was 2 years (range, 0.5 to 7 years). Reported reasons for euthanasia were related to progression of clinical signs and included worsening lameness and reluctance to move (5 horses), persistent lameness (3), inability to bend the neck in any direction (1), and ataxia (1). One horse was euthanized following an acute episode of equine protozoal myeloencephalitis. The remaining 5 horses were alive at the time of the present study; median follow-up time for these horses was 15.5 months (range, 7 months to 5 years).
Discussion
Results of the present study suggested that horses may develop a bone fragility disorder characterized clinically by an unlocalizable lameness that progressed in severity and distribution, eventually necessitating euthanasia in most horses. The disease was characterized scintigraphically by multiple sites of IRU involving the axial skeleton and proximal portion of the appendicular skeleton. Clinicopathologic findings were largely unremarkable. Radiographic and ultrasonographic abnormalities were detectable in some, but not all, affected horses.
A previous report1 described 17 horses from Monterey Bay or the Carmel Peninsula in northern California with a similar, insidious, chronically progressive debilitating bone disorder. Horses in this previous study were older (median, 17 years) than horses in the present study (median, 10 years) and had more advanced skeletal abnormalities. However, there were multiple similarities between the 2 reports. In particular, multiple bones were affected in most horses in both reports, with bones of the axial skeleton and proximal portion of the appendicular skeleton affected most frequently. In addition, some horses in both reports had severe deformation of the scapulae, lordosis, or degenerative changes of the cervical vertebrae. Horses were included in the previous report only if they had pulmonary silicosis and had been exposed to Miocene Monterey shale, whereas only 3 horses in the present study were definitively found to have pulmonary silicosis. Nevertheless, we speculate that horses in the present report had less severe clinical manifestations of the same bone disease described in the previous report.
The scapulae and ribs were the most commonly affected bones in horses in the present report, with the flat bones of the pelvis, the cervical vertebrae, and the sternebrae less commonly affected. The geometry and composition of the flat bones may make them more susceptible to remodeling,5 compared with the long bones, and this may help explain the distribution of lesions. Lateral bowing of the scapulae and swayback conformation seen in 3 horses in the present report may have developed secondary to scapular, rib, and vertebral fragility with subsequent remodeling. There was no apparent progression of lesion distribution, in that the distribution of lesions in younger horses in the present study was similar to the distribution in older horses.
In the present study, radiographic and ultrasonographic examination of areas of IRU did not always reveal abnormalities. In particular, scapular and rib abnormalities were detected radiographically or ultrasonographically in only the 3 horses with the most severe clinical abnormalities. On radiographic images, superimposition of thoracic structures on the ribs and scapulae made it difficult to visualize pathologic abnormalities. Thickening of the scapular spine was the most common ultrasonographic abnormality, but was seen inconsistently.
Subjectively, the severity of clinical signs, including severity of visual evidence of bone deformity, was not related to the intensity or distribution of radiopharmaceutical uptake in horses in the present study. Two horses that had extensive scapular bowing, lordosis, and cervical stiffness, for instance, had sites of only mild to moderate IRU. In contrast, 3 horses with relatively mild lameness had sites of IRU compatible with fracture. Areas of IRU represent sites undergoing acute remodeling secondary to fractures or pseudofractures. However, sites undergoing slow remodeling may not be detected as areas of IRU, and a lack of abnormalities on scintigraphic images does not rule out metabolic bone disease.6 Thus, even though horses in the present study typically had multiple sites of IRU, the true extent of affected regions may have been underestimated. Other causes of IRU affecting multiple sites of the skeleton include hypertrophic osteopathy,7 enostosis-like lesions,8 skeletal muscle injury typical of early rhabdomyolysis,9 and neoplastic conditions including lymphosarcoma9 and fibrosarcoma.10 All of these conditions have clinicopathologic findings that are not characteristic of the bone disease seen in horses in the present report.
Horses in the present report were typically examined because of an unlocalizable lameness affecting 1 or more limbs. Fourteen of the 16 horses were examined because of a forelimb lameness, although 4 of these 14 horses also had evidence of hind limb lameness. The cause of the lameness could not be localized by means of diagnostic nerve or intra-articular blocks and worsened with time. Shoulder and gluteal muscle atrophy were observed in some horses without visual evidence of skeletal deformities. The most dramatic bone deformities were evident in older horses and apparently developed over months to years. Overlapping periods of injury and repair could account for variations in severity of lameness in individual horses and the variable response to analgesics.
Progression of the disease at the original site and extension to previously unaffected sites was evident in 3 of 5 horses that underwent follow-up scintigraphy between 4 weeks and 2 years after the first examination. In contrast, no changes were evident in the other 2 horses that underwent follow-up scintigraphy.
For all horses in the present report, treatment was only palliative. Current management recommendations include judicious use of NSAIDs to alleviate pain and exercise restriction until chronic discomfort or pathologic fractures dictate euthanasia. Unfortunately, until the underlying cause of the disease is identified, specific treatment cannot be recommended. A variety of measures to optimize bone mineral density are used in human patients with osteoporotic disease in an effort to reduce the risk of pathologic fractures,11 including dietary modifications; exercise; hormone replacement therapy; and administration of bone-modulating drugs such as bisphosphonates, calcitonin, and selective estrogen receptor modulators. It is possible that some of these measures may be effective in horses also. In particular, use of tiludronate in horses with this condition is worthy of further investigation, as bisphosphonates are effective in reducing pain and degenerative bone changes associated with similar conditions involving remodeling of bone in human patients.11
The etiopathogenesis of the bone fragility disorder in the horses described in the present report remains undetermined. The finding that 3 horses had clinical and cytologic evidence of pulmonary silicosis and that an additional 4 horses had radiographic findings typical of pulmonary silicosis12 suggests that this may have played a role. Many affected horses originated from areas where they may have been exposed to Miocene Monterey shale soil, which contains a high concentration of the fibrogenic and cytotoxic cristobalite form of silicate that causes pulmonary silicosis in horses.13
Generalized osteoporosis in horses has previously been associated with excessive intake of zinc and cadmium from forage grown around a smelting plant.14 The lack of joint, osteochondral, and renal lesions and the lack of exposure to zinc and cadmium, however, make this an unlikely cause of the bone fragility disorder described in horses in the present study. Metabolic bone disease can develop in horses in association with long-term administration of corticosteroids, deficiencies in vitamin D and calcium, and primary and secondary hyperparathyroidism.15 Again, however, there was no evidence of these conditions in horses described in the present report. The slightly high serum parathyroid hormone activities in 3 horses were deemed to be clinically unimportant when 3 clinically normal horses from a different geographic location were found to also have slightly high activities. Whereas the diets of horses in the present report were not determined, the lack of other clinical signs associated with nutritional hyperparathyroidism makes it unlikely that nutrition played a role.
ABBREVIATION
| IRU | Increased radiopharmaceutical uptake |
Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, Mich
Technicare Omega 500 gamma camera, Technicare Corp, Cleveland, Ohio.
Nuclear Mac 5.2.1, Scientific Imaging, Littleton, Colo.
FCR 5000, Fujifilm Medical Systems USA, Valencia, Calif.
Biosound Technos, Universal Ultrasound, Bedford Hills, NY.
Osteon, Platinum Performance, Buellton, Calif.
Adequan, Luitpold Pharmaceuticals Inc, Shirley, NY.
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