Recombinant human bone morphogenetic protein-2 in absorbable collagen sponge enhances bone healing of tibial osteotomies in dogs

OBJECTIVE: To compare the efficacy of 2 doses of recombinant human bone morphogenetic protein-2 (rhBMP-2) on tibial osteotomy healing in dogs. STUDY DESIGN: Experimental, randomized complete block (n=7). ANIMALS: Adult female dogs (n=21). METHODS: Right midshaft tibial osteotomies were created and stabilized with a 1-mm gap using type I external fixators. Seven dogs were untreated controls and 14 with osteotomies were treated with either 0.05 or 0.2 mg/mL rhBMP-2 delivered in an absorbable collagen sponge (ACS). At 8 weeks, dogs were euthanatized and bones were mechanically tested and examined by microscopy. RESULTS: Bone healing based on radiographic scoring, was significantly improved in dogs treated with 0.2 mg/mL of rhBMP-2 compared with the other groups; these tibiae were also significantly stronger and stiffer than 0.05 mg/mL rhBMP-2 and control osteotomized tibiae. Histologic scores were significantly better for 0.2 mg/mL rhBMP-2 group than 0.05 mg/mL rhBMP-2 group, but neither was significantly different from control. CONCLUSIONS: rhBMP-2 in ACS at a concentration of 0.2 mg/mL improves healing of tibial osteotomies in dogs compared with untreated controls and 0.05 mg/mL rhBMP-2 based on force plate analysis and radiographic evaluation. This was not confirmed histologically but treated bones had improved mechanical properties at 8 weeks. CLINICAL RELEVANCE: After a long bone fracture, dogs may face a long recovery period before full return of limb function. rhBMP-2, in association with good fracture fixation principles, may enhance bone healing in dogs with diaphyseal fractures.     

Comparison of two doses of recombinant human bone morphogenetic protein in absorbable collagen sponges for bone healing in dogs

OBJECTIVE: To determine the effects of 2 doses of recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge (rhBMP-2/ACS) on bone healing in dogs. ANIMALS: 27 adult dogs. PROCEDURES: Dogs underwent a mid-diaphyseal (1-mm) tibial osteotomy (stabilized with external skeletal fixation) and received an ACS containing 0.28 mg (0.2 mg/mL) or 0.56 mg (0.4 mg/mL) of rhBMP-2 or no treatment (control dogs). All dogs were examined daily; bone healing was assessed via radiography and subjective lameness evaluation every 2 weeks. After euthanasia at 8 weeks, tibiae were evaluated biomechanically and histologically. RESULTS: Control dogs required antimicrobial treatment for pin-site-related complications more frequently than did rhBMP-2/ACS-treated dogs. At 4 and 6 weeks, weight bearing was greater in dogs treated with rhBMP-2/ACS (0.2 mg/mL) than in control dogs, albeit not significantly. Compared with control treatment, both doses of rhBMP-2/ACS accelerated osteotomy healing at 4, 6, and 8 weeks, and the 0.2 mg/mL dose enhanced healing at 2 weeks; healing at 6 weeks was greater for the lower-dose treatment than for the higher-dose treatment. Histologically, healing at 8 weeks was significantly improved for both rhBMP-2/ACS treatments, compared with control treatment. Among groups, biomechanical variables did not differ, although less osteotomy-site failures occurred in rhBMP-2/ACS-treated groups. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs that underwent tibial osteotomy, rhBMP-2/ACS (0.2 mg/mL) appeared to accelerate bone healing and reduce lameness (compared with control treatment) and apparently augmented bone healing more than rhBMP-2/ACS (0.4 mg/mL). Compared with control dogs, rhBMP-2/ACS-treated dogs required antimicrobial treatments less frequently.     

Clinical application of recombinant human bone morphogenetic protein-2 in 4 dogs

OBJECTIVE: To describe outcome in dogs with insufficient bone healing treated with recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Retrospective study. ANIMALS: Four dogs clinically affected with delayed union or nonunion bone healing. METHODS: Medical records were reviewed for signalment, clinical problem, treatment, and outcome. RESULTS: Four dogs that had delayed- or nonunion of bone fracture, osteotomy, or arthrodesis were treated with either minimally invasive, fluoroscopically guided, percutaneous administration or direct surgical application of rhBMP-2. Doses used ranged from 0.2 to 1.6 mg of rhBMP-2. In 3 dogs, a calcium phosphate matrix (CPM) carrier was used whereas in 1 dog commercially prepared rhBMP-2 impregnated in an absorbable collagen sponge (INFUSE Bone Graft) was used. This latter dog had osteomyelitis associated with implant infection before rhBMP-2 administration. Rapid radiographic union was noted in all dogs with excellent long-term outcome. Adverse effects were minimal and included transient worsening of lameness after percutaneous administration of rhBMP-2 in 2 dogs. CONCLUSIONS: rhBMP-2 stimulated rapid bone formation at delayed- or nonunion sites resulting in radiographic bone union with minimal adverse effects and excellent long-term outcome in 4 dogs. CLINICAL RELEVANCE: Direct intraoperative administration or fluoroscopically guided, minimally invasive delivery of rhBMP-2 may be an effective treatment modality for bone delayed- or nonunions and could potentially be used to stimulate new bone production in a variety of orthopedic surgical conditions in dogs.     

Mandibular reconstruction of a partial hemimandibulectomy in a dog with severe malocclusion

OBJECTIVE: To report treatment of severe mandibular malocclusion (after left partial hemimandibulectomy, approximately 7 cm gap). STUDY DESIGN: Clinical report. ANIMALS: A 14-month-old golden retriever. METHODS: After corrective osteotomy of the right horizontal mandibular ramus, normal occlusion was reestablished and temporarily maintained while both mandibles were stabilized by miniplates on the lateral alveolar surface spanning the bilateral mandibular defects (right=1.5 cm, left=7 cm). A fenestrated, monocortical rib graft was positioned beneath the left gingival surface to protect the synthetic graft, which was secured to the miniplate. A mandibular reconstruction plate (right) and a locking mandibular reconstruction plate (left) were secured to the ventral borders of the mandibles. Recombinant bone morphogenetic protein-2 delivered in collagen tricalcium phosphate sponges (rhBMP-2 collagen-TCP sponge) was inserted into both mandibular defects. RESULTS: New bone formation was identified at 3 months and bony remodeling was evident at recheck examinations up to 4 years. Scintigraphy (6 months, 1 year) confirmed graft revascularization and viability. Bone collected (1 year) from the left defect site had robust new bone formation and evidence of continued remodeling. Only minor complications were encountered during the postoperative period and were easily resolved. CONCLUSIONS: Reconstruction of a large mandibular defect was facilitated by use of an osteoinductive factor (rhBMP-2 collagen-TCP sponge) as a graft substitute. CLINICAL RELEVANCE: One-step salvage and reconstruction facilitated by use of an osteoinductive factor, as a graft substitute, may be an alternative strategy for repair of large mandibular defects.     

Immediate mandibular reconstruction of a 5 cm defect using rhBMP-2 after partial mandibulectomy in a dog

Objective— To report treatment of a complex odontoma of the mandible by partial mandibulectomy and immediate surgical reconstruction using bridging plate fixation with a synthetic graft.
Study Design— Clinical case report.
Animals— A 4-year-old male castrated cocker spaniel.
Methods— Immediate reconstruction of the left mandible (5 cm gap) was performed after complete excision of a complex odontoma. Locking plate fixation was applied immediately before complete excision of the mass. Fixation was removed, then after partial mandibulectomy, including all abnormal tissue, restored to achieve occlusion. The resulting mandibular defect was filled with recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an absorbable collagen sponge containing hydroxyapatite/tricalcium phosphate granules (compression resistant matrix [CRM]).
Results— New bone growth was evident radiographically and on palpation at 3 months. Bony remodeling was evident during follow-up examinations up to 26 months. Bone collected by biopsy at the graft site at 7 months had robust new bone formation and evidence of continued remodeling. Only minor complications (repeated intraoral plate exposure) were encountered postoperatively and were easily resolved.
Conclusions— An osteoinductive factor (rhBMP-2/CRM) was successfully used as a graft substitute in immediate reconstruction of a large mandibular defect.
Clinical Relevance— Immediate reconstruction of large mandibular defects with osteoinductive materials as a graft substitute may be a viable alternative to partial mandibular resection or radiation therapy for benign odontogenic tumors in dogs.     

Clinical Use of Recombinant Human Bone Morphogenic Protein-2 in a Whooping Crane (Grus americana)

Objective— To report use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as adjunctive therapy for treatment of a comminuted, open, proximal humeral fracture in an avian species.
Study Design— Clinical report.
Animals— A 3.5-month-old male whooping crane ( Grus americana ).
Methods— An open, severely comminuted humeral facture was stabilized with an intramuscular (IM) pin/type IA external skeletal fixator with tie-in configuration. rhBMP-2 was applied in a calcium phosphate matrix (CPM) paste directly to the fracture site as a bone graft substitute. Radiographic evidence of bone healing was monitored for 14 weeks.
Results— Substantial bony callus was evident at 4 weeks and at 8 weeks there was bridging callus with obvious bony remodeling. The fixation was destabilized at 9 weeks by IM pin removal, bone healing progressed and the fixator was removed at 11 weeks. By 14 weeks both cortices had been re-established with continued callus remodeling evident.
Conclusion— rhBMP-2, applied in a CPM paste, was used as a bone graft substitute in the treatment of a comminuted, open humeral fracture in a whooping crane.
Clinical Relevance— Use of rhBMP-2/CPM should be considered in treatment of avian fractures.     

重组人骨形态发生蛋白2复合物对犬胫骨骨折愈合中4种相关细胞因子的作用

研究重组人骨形态发生蛋白2(rhBMP-2)、碱性成纤维细胞生长因子(bFGF)、纤维蛋白凝胶(FG)与妥布霉素复合物加速骨折愈合。bFGF与rhBMP-2和妥布霉素以纤维蛋白胶为载体复合,将具有抗生素缓释系统的复合物注入犬胫骨骨折处,并做内固定,于术后第2周,采集犬胫骨骨折处样品,每隔2周采集1次,共采集4次,将每次采集的样品制成组织切片,采用免疫组织化学的方法检测4种因子,并对组织切片进行分析,用多功能真彩色细胞图象分析管理系统,分析所得数据用SPSS18.0版统计软件进行统计学分析。血管内皮细胞生长因子(VEGF)在试验组第2周表达强阳性,而对照组阳性表达较弱;前4周,试验组血小板源性生长因子(PDGF)阳性率呈上升趋势,强于对照组;前8周,试验组胰岛素样生长因子(IGF)和转化生长因子-β1(TGF-β1)阳性率均高于对照组。说明bFGF与rhBMP-2和妥布霉素以纤维蛋白胶为载体的复合物在骨折愈合具有中促进细胞增殖、黏附、趋化、分化,以及骨折末端血管生长和形成的作用。     

Clinical application of recombinant human bone morphogenetic protein in cats and dogs: A review of 13 cases

Databases (2001–2008) for cases in which recombinant bone morphogenetic protein (rhBMP) was used to aid in management of orthopedic disease were reviewed and cases were categorized as non-unions, delayed unions, and cases expected to heal with difficulty. If follow-up in the medical record was < 6 mo for live animals, owners were surveyed by telephone. Thirteen cases (11 dogs, 2 cats) were identified; OP-1 (rhBMP-7) was used in 3 cases and INFUSE (rhBMP-2) in 10. Mean time from injury to rhBMP use for non- and delayed union cases was 156 d; mean time from rhBMP use to radiographic healing was 101 d. No systemic side effects were reported. All patients achieved clinical and radiographic bone union following rhBMP administration. Recombinant human BMP was used in 13 veterinary patients to successfully achieve bone union without serious deleterious effects in a variety of clinical applications.     

Treatment of basophilic leukemia in a dog.

Basophilic leukemia in a 6-year-old dog was characterized by marked splenomegaly, anemia, and leukocytosis in which 89% of the circulating leukocytes were basophilis. After an attempt at busulfan therapy, the dog was treated with hydroxyurea and was maintained on this drug for 2 months. After withdrawl of hydroxyurea, the dog remained in remission and was still in remission at the time of writing (8 months later).     

Sequential opportunistic infections in two German Shepherd dogs

Two German Shepherd dogs with sequential opportunistic infections are described. The first was a 2-year-old male with cryptococcal rhinitis that spread to involve the optic nerves and brain. It was successfully treated with combination therapy utilising amphotericin B administered for 2 years, but the dog developed a disseminated Aspergillus deflectus infection 5 years later and was euthanased. The second case was a 4-year-old male that presented for a severe, deep-seated infection of the right antebrachium, with gradual extension to contiguous tissues. Neosartorya fischeri (anamorph; Aspergillus fischerianus) was isolated in pure culture and detected in histological sections. The infection was refractory to itraconazole, but resolved after amputation of the affected limb. Five months later, the dog developed a localised cutaneous lesion on the proximal pelvic limb, from which Pythium insidiosum was isolated and then visualised in tissue sections, together with a structure thought to be grass seed. This lesion was treated by wide surgical resection, although it was reported that the dog died of disseminated disease some months later. These cases provide further circumstantial evidence that young adult German Shepherd dogs have a predilection to developing invasive infections with fungi and other saprophytic pathogens.     

Endodontic treatment and metal crown restoration of a fractured maxillary right fourth premolar tooth: a case report

A 2 year-old, spayed female Shetland sheepdog presented with a fractured maxillary right fourth premolar tooth during oral examination for a dental prophylaxis. Seven months after conventional root canal therapy was performed, the tooth was prepared for non-precious metal, full crown restoration, which was cemented in place 1 month after crown margin preparation. During re-examination for an unrelated problem 6 months later, the metal crown was in place and there was no evidence of further fracture of the tooth.     

Total venous inflow occlusion and pericardial auto-graft reconstruction for right atrial hemangiosarcoma resection in a dog

A sizeable right atrial hemangiosarcoma in a 6-year-old Bordeaux dog, World Health Organization (WHO) stage 2, was excised using total venous inflow occlusion. The defect was restored with a non-vascularized pericardial auto-graft. The dog had a disease-free interval of 7 mo. The dog was euthanized 9 months later, at which time there were distant metastases but no indication of local recurrence.     

Cisplatin chemotherapy for metastatic squamous cell carcinoma in two dogs

Cisplatin was used successfully to treat 2 dogs with metastatic squamous cell carcinoma. One dog was observed to have a complete remission and died of unrelated causes 23 months later. The other dog had a partial remission of the tumor, but relapsed and was euthanatized 4 1/2 months after the beginning of treatment. Both dogs tolerated the treatment well.     

Excretion and reexcretion of thermosensitive and wild-type strains of infectious bovine rhinotracheitis virus after co-infection or two successive infections

Twelve cattle were divided into 2 groups. The first was intranasally co-infected with 2 strains of infectious bovine rhinotracheitis virus (Bovine herpesvirus 1; BHV 1): the thermosensitive vaccine strain IBR/ts RLB106 and a Belgian field isolate IBR/Cu5. Reactivation of BHV 1 was induced by dexamethasone treatment 2 months later and again 5 months later for 3 animals that only reexcreted small quantities of virus during the first dexamethasone treatment. The second group was intranasally infected with IBR/Cu5. Two months later, an attempt to reinfect this group with IBR/ts RLB106 failed. Four months after the primary infection, these cattle were treated with dexamethasone. Except after reinfection and at the beginning or the end of the (re)excretion periods, excreted and reexcreted viruses replicated at 35, 37 and 40 degrees C, indicating the presence of the wild-type virus. Only one isolate, out of 116 cloned from the nasal exudates collected during the excretion and reexcretion periods, expressed the thermosensitive phenotype. This isolate was characterized by its mean plaque size as the IBR/ts RLB106 strain. The epizootiological significance of these findings is discussed, with emphasis on the weak spreading capacity of the ts vaccine strain and the possibility of emergence of recombinant viruses.     

Difference in age at first conception between early and late litters of feral raccoon (Procyon lotor) in Kanagawa prefecture

Due to the long parturition period of raccoons, we assumed that age at first conception of late born females was later than that of early born females. From March 2005 to September 2008, 201 females estimated to be younger than 24 months were separated into early- and late-born groups on the basis of their estimated birth month (to the nearest 2 months), and parous status and body mass index (BMI) were examined. Age at first conception of late-born females (over 18 months old) was estimated to be later than that of early-born females (over 12 months old). The average BMI in early-born individuals at 12 months old might have affected their ability to conceive because of body fat deposition.     

Use of a sustained release preparation of clotrimazole to treat dermatophytosis in a siamang (Hylobates syndactylus).

In November 2004, an adult male siamang (Hylobates syndactylus) from The Tisch Family Zoological Gardens-Jerusalem Biblical Zoo (Israel) presented with skin lesions on various body parts. Lesions consisted of alopecia and dry, crusty areas of hyperkeratosis. A diagnosis of dermatophytosis due to Microsporum canis was determined by fungal culture of skin scraping taken from the edge of several lesions. Treatment with various oral and topical antifungal agents such as griseofluvin, itraconozole, and lufenuron resulted in the resolution of most lesions and a decrease in size of the single remaining lesion, which continued to be culture positive for M. canis. The animal was anesthetized and an experimental sustained-release clotrimazole varnish was painted directly on the lesion. Initially there was no change in the lesion, and 2 months later a slightly altered formula was applied under anesthesia. One month later, the lesion began to reduce in size; 3 months after the start of treatment, although 2 years after the onset of clinical signs, the lesion resolved. Minimizing the number of treatments is always an advantage when dealing with exotic animals or zoological collections.     

Prevalence of serum neutralising antibody to equine rhinitis A virus (ERAV), equine rhinitis B virus 1 (ERBV1) and ERBV2

The objective of this study was to determine the incidence of serum neutralising (SN) antibody to ERAV, ERBV1 and ERBV2 in a population of horses from birth to 22 years of age. The prevalences of ERAV, ERBV1 and ERBV2 SN antibodies in 381 sera obtained from 291 horses were 37%, 83% and 66%, respectively. ERAV, ERBV1 and ERBV2 maternal antibody was present in foals 12 h postsuckling but by 10-12 months, ERAV SN antibody was not detected in any of the horses, while ERBV1 and ERBV2 SN antibodies were common (83% and 100%, respectively). Sera were obtained from 44 Thoroughbred horses when they were newly introduced into a training centre when their average age was 23 months and a second sample was obtained approximately 7 months later. ERAV SN antibody was present in 8 (18%) when first bled and in 27 (61%) when tested 7 months later. Accordingly 19 of the 44 horses (43%) seroconverted to ERAV within 7 months of entering the training stable. Among all the horses the average ERAV SN antibody titre was relatively high (3796) and in contrast, ERBV1 and ERBV2 titres were relatively low (average 84 and 45, respectively) and often fell to below detectable levels over time and at a rate comparable to new seroconversions in the same group of horses.     

Thoracic vertebral osteochondroma in a cat

A thoracic vertebral (T5) osteochondroma was discovered in a 1 1/2-year-old male blue Persian cat with a history of acute hind limb paresis. Myelography revealed a mass on the dorsal surface of the vertebral body, which resulted in dorsal compression of the spinal cord. A dorsal laminectomy was performed, and the mass was rongeured entirely from the vertebral body. Although the cat's progress was initially slow after surgery, its neurologic status was assessed to be near normal, 15 months later.     

Nasal obstruction caused by cystic nasal conchae in cattle

Four Holstein heifers were found to have partial nasal obstruction caused by bilateral cystic conchae. Three of the heifers (age range, 4 to 6 months) had a history of progressive nasal obstruction since near birth, were affected severely, and required surgical management. Each of 2 surgical procedures, a bilateral dorsolateral nasal flap approach and a dorsal nasal flap approach, was used successfully. The fourth heifer, which was 15 months old, had signs of nasal obstruction since shortly after birth, but was affected only mildly and was not treated. Follow-up information obtained 10 to 37 months later revealed that all cattle were considered normal and had no signs of nasal obstruction. In each case, a developmental problem or malformation of the ventral nasal concha resulting in cystic enlargement was suspected. The onset of clinical signs early in life and the bilateral nature suggested that the defect was of congenital origin.     

一例黑熊尺骨桡骨开放性骨折的诊疗

2008年9月7日,哈尔滨市某实验林场养熊场1只8月龄雄性黑熊因左前肢被大熊咬伤而就诊。经体格检查发现小黑熊左前肢尺骨和桡骨开放性骨折。采用内固定法治疗,2个月后小黑熊痊愈。