Joint-dependent response to impact and implications for post-traumatic osteoarthritis.

OBJECTIVE: The prevalence of osteoarthritis (OA) varies between joints. Cartilage in eight different joints was evaluated to elucidate the disparate susceptibilities between joints to post-traumatic OA (PTOA) and provide evidence for joint-specific clinical treatments. The hypothesis was that cartilage in different joints would have varying cell death and anabolic gene expression profiles after injury. METHODS: Adult equine cartilage explants were harvested from shoulder (SH), elbow (EL), carpal (CA), metacarpophalangeal (MC), patellofemoral (FP), tarsal (TA), metatarsophalangeal (MT), and proximal interphalangeal (PP) joints, and injured by loading with 30 MPa within 1 s. Fractional dissipated energy, cell density, cell death, and gene expression were quantified. RESULTS: PP had the highest fractional dissipated energy (94%, 95% confidence interval [CI] 88 to 101%). Cell density was highest in the superficial zone in all samples, with MC and MT having the highest peak density. Injured samples had significantly increased cell death (13.5%, 95% CI 9.1 to 17.9%) than non-injured samples (6.8%, 95% CI 2.5 to 11.1%, P = 0.016); however, cell death after injury was not significantly different between joints. Gene expression was significantly different between joints. CD-RAP expression in normal cartilage was lowest in FP (Cp = 21, 95% CI -80 to 122). After injury, the change in CD-RAP expression increased and was highest in FP (147% relative increase after injury, 95% CI 64 to 213). CONCLUSION: Different joints have different baseline characteristics, including cell density and gene expression, and responses to injury, including energy dissipation and gene expression. These unique characteristics may explain differences in OA prevalence and suggest differences in susceptibility to PTOA. CLINICAL RELEVANCE: Understanding differences in the response to injury and potential susceptibility to OA can lead to the development of preventative or treatment strategies. KEY TERMS: Gene expression, cartilage injury, chondrocyte, multiphoton microscopy, cartilage biomechanical properties, PTOA. WHAT IS KNOWN ABOUT THE SUBJECT: The prevalence of OA is variable among joints; however, most laboratory studies are performed on a single joint - most commonly the knee, and extrapolated to other joints such as the ankle or shoulder. A small number of studies have compared knee and ankle cartilage and reported differences in mechanical properties and gene expression. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: There are differences in baseline cell density and gene expression, and differences in response to injury, including gene expression and cell death. This suggests that there are inherent differences leading to varying susceptibilities in OA prevalence among joints. Joint-specific treatments may improve OA therapies.

A tortoiseshell male cat: chromosome analysis and histologic examination of the testis.

Tortoiseshell coat color is normally restricted to female cats due to X-linkage of the gene that encodes the orange coat color. Tortoiseshell male cats do, however, occur at a low frequency among tortoiseshell cats because of chromosome aberrations similar to the Klinefelter syndrome in man: the extra X chromosome of a 39,XXY karyotype introduces the possibility of an orange and a non-orange allele which produce the mixture of orange and non-orange coat spotting known as tortoiseshell. We analyzed the chromosome complement of a fibroblast culture and did histological examinations of testicular tissue from a tortoiseshell male cat referred to us. Chromosome analysis using RBA-banding consistently revealed a 39,XXY karyotype. Histological examinations of testis biopsies from this cat showed degeneration of the tubules, hyperplasia of the interstitial tissue, and complete loss of germ cells. Immunostaining using anti-vimentin and anti-VASA (DDX4) showed that only Sertoli cells and no germ cells were observed in the testicular tubules. As no sign of spermatogenesis was detected, we conclude that this is a classic case of a sterile, male tortoiseshell cat with a 39,XXY chromosome complement.

Synovial folds in equine articular process joints.

REASONS FOR PERFORMING STUDY: Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses. OBJECTIVES: The objective of this explorative study was to determine the frequency of synovial folds in equine cervical articular process joints and to provide a characterisation of the size and morphology of the synovial folds. METHODS: Equine cervical articular process joints from 6 horses were included in the study, ranging from cervical vertebra 2 (C2) to cervical vertebra 7 (C7) bilaterally. The articular process joints were dissected, and the cranial and caudal synovial folds of each joint were measured and embedded in paraffin. Synovial folds were analysed histologically and classified according to type, as adipose, fibrous and mixed type. Factors potentially influencing fold size were investigated, including joint number (from C2/C3 to C6/C7), fold type, position of fold within the joint (cranial or caudal) and side of neck (right or left). RESULTS: Synovial folds were identified in 98% of cervical articular process joints examined. The width of the synovial folds varied from 4 to 41 mm, and the height from 1 to 17.8 mm. Thirty-eight per cent of the synovial folds were of adipose type, 41% of fibrous type and 21% of mixed type. Synovial fold size was significantly influenced by the side of the neck and fold type. CONCLUSIONS AND POTENTIAL RELEVANCE: This study provides a characterisation of the frequency, size and morphology of equine cervical synovial folds in 6 horses. Synovial folds were present in 98% of the cervical articular process joints examined, and the size of the synovial folds indicates that they could be damaged by acute injury or chronic disease in the cervical articular process joints.

Distances between thoracic spinous processes in Warmblood foals: a radiographic study.

REASON FOR PERFORMING STUDY: The aetiological factors behind impinged or overriding of dorsal spinous processes ('kissing spine syndrome', KSS) are not clearly understood. Back conformation, breed, age, training and gender may play important roles in this condition. Radiographic changes vary and abnormalities are seen in many clinically normal horses, but the conclusion of previous studies in mature horses is that interspinous spaces <4 mm are considered too narrow and potentially indicative of KSS. OBJECTIVES: To evaluate whether narrowing of the interspinous space was present in a population of normal Warmblood foals. MATERIALS AND METHODS: The mean interspinous space width in the area of T10-L1 was measured on radiographs from 25 Warmblood foals aged 9-88 days. RESULTS: Mean +/- s.d. interspinous space width was found to be between 5.9 +/- 1.2 and 8.9 +/- 2.6 mm with the narrowest space in the area T16-T17 and the widest space in T10-T12. No interspinous spaces were <4 mm wide. Gender and location of the interspinous space significantly affected the width of the distance between the spinous processes. CONCLUSIONS AND POTENTIAL RELEVANCE: In this study none of the interspinous spaces were <4 mm and therefore none of the foals showed signs of impinged or overriding of dorsal spinous processes known as KSS based on the current definitions. Consequently, in this population, there did not appear to be a congenital narrowing of the interspinous space. However, long-term follow-up studies, including detailed information on imposed factors such as training, are needed in order to further elucidate a possible congenital component in the aetiology of KSS.

Accuracy of ultrasound-guided injections of thoracolumbar articular process joints in horses: a cadaveric study.

REASONS FOR PERFORMING STUDY: Arthrosis of the articular process joints (APJs) in the caudal thoracolumbar region of horses may cause back pain and subsequent reduced performance or lameness. Ultrasound-guided injections of the APJs of the equine back have been described only briefly in the literature. OBJECTIVES: To evaluate factors affecting the accuracy of intra-articular injections of the APJs in the caudal thoracolumbar region. METHODS: One-hundred-and-fifty-four injections with blue dye were performed on APJs including the T14-L6 region in 12 horses subjected to euthanasia for reasons unrelated to back problems. The backs were subsequently dissected to verify the location of the injectate in relation to the APJs. RESULTS: Twenty-seven percent of the injections were found to be intra-articular and a total of 77% found to be within 2 mm of the joint capsule including the intra-articular deposits. Application of a medial approach and 18 gauge needle were significantly associated with an intra-articular injection or deposition close to the joint capsule. Operator, APJ (location) and back number (chronological) did not significantly affect the accuracy of injection. CONCLUSIONS AND POTENTIAL RELEVANCE: Injection of the vertebral APJ in the thoracolumbar region using ultrasound guidance is a reliable method, as most of the injections were either in or within 2 mm of the joint. Based on the findings of this cadaver study, the medial approach is expected to be the most accurate in live horses. Further investigations are required to evaluate the diagnostic and therapeutic potential of this method in clinical practice.

Cartilage-derived retinoic acid-sensitive protein in equine synovial fluid from healthy and diseased joints.

REASONS FOR PERFORMING STUDY: More sensitive and specific diagnostic methods for early detection of changes in the joint cartilage are needed. Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a potential marker of cartilage synthesis and regeneration. This is the first study on equine CD-RAP. OBJECTIVES: To evaluate the ability of a commercially available human sandwich ELISA assay to detect equine CD-RAP in synovial fluid from healthy and diseased joints. METHODS: Synovial fluid was collected from 28 horses with no signs of joint disease and from 5 with induced inflammatory arthritis. CD-RAP concentrations were measured using a human CD-RAP ELISA. Intra- and interassay imprecision of the assay were evaluated by multiple measurements on pools of equine synovial fluid. Assay inaccuracy was determined by linearity under dilution. RESULTS: The assay showed moderate to large intra- and interassay variation when applied to equine synovial fluid. Equine CD-RAP was detected in synovial fluid from healthy horses ranged at 8.2-52 ng/ml. Repeated arthrocentesis (after injection of isotonic saline), age, joint or gender did not significantly affect CD-RAP concentrations. Twelve hours after intra-articular injection of lipopolysaccharide, concentrations of CD-RAP were significantly lower than after injection of isotonic saline and remained significantly lower until the end of the study at 144 h. CONCLUSION AND POTENTIAL RELEVANCE: The assay is suitable for longitudinal monitoring of CD-RAP concentration in individual horses. Disease significantly influenced CD-RAP levels. Similar to previous results obtained in man, CD-RAP seems to be a marker of cartilage synthesis and/or regeneration in horses.

Ultrasonography of the equine cervical region: a descriptive study in eight horses.

REASONS FOR PERFORMING STUDY: In equine patients, the cause of clinical signs possibly related to the cervical region is often difficult to diagnose. Ultrasonography allows quick and noninvasive visualisation, but reference material of the normal equine neck is needed. OBJECTIVES: To describe and document the normal ultrasonographic appearance of transverse scans in the cervical region with emphasis on the synovial articular facet joints, cervical vertebrae and paravertebral structures; and further, to provide images of frozen cross-sections for anatomical reference. METHODS: A study describing the normal ultrasonographic appearance of the cervical anatomy was performed. Transverse scans were obtained from second cervical vertebra (C2) to first thoracic vertebra (T1). Post mortem photographs of frozen cross-sections were obtained as anatomical reference. RESULTS: The structures were clearly visualised by ultrasonography and consistency was found between ultrasonographic images and corresponding cross-sectional anatomy. The articular facets varied between horses and facets (C2 to T1). Discrepancy in the existing anatomical descriptions was found. CONCLUSIONS AND POTENTIAL RELEVANCE: The anatomical and ultrasonographic description provides a reference for ultrasonographic evaluation of equine cervical facet joints, vertebrae and paravertebral structures. The findings and variations found are considered to reflect the naturally occurring variations in horses.

Accuracy of ultrasound-guided intra-articular injection of cervical facet joints in horses: a cadaveric study.

REASONS FOR PERFORMING STUDY: Intra-articular facet joint injection is an established diagnostic procedure in human medicine but there are no reports on its reliability in equine practice. OBJECTIVES: To investigate the accuracy of ultrasound-guided intra-articular injections of the cervical facet joints and to estimate factors influencing the accuracy. METHODS: Sixty injections with blue dye were performed on the facet joints between 2nd and 7th cervical vertebra (C2-C7) on horses subjected to euthanasia for nonorthopaedic reasons. The facet joints were subsequently dissected to verify accuracy of deposition. RESULTS: Seventy-two percent of the injections were found to be intra-articular, 17% were intracapsular and a total of 98% were within 1 mm of the joint capsule. There was a marked effect of gained experience (P < 0.01), but not of other factors tested. CONCLUSIONS AND POTENTIAL RELEVANCE: The results of the present study do not translate directly to injections performed in live horses, but they indicate that the method can be applied as a diagnostic as well as therapeutic procedure in C2 to C7 and that is advisable to practise injections on cadaver specimens before applying the technique.

Cat-scratch disease simulating Histiocytosis X.

Cat-scratch disease is a self-limited condition commonly causing a benign chronic lymphadenopathy in children. Osteolytic lesions are a rare complication, but have been previously reported. We report a case of a solitary osteolytic lesion of the skull whose clinical, radiographic and pathological features were initially interpreted as being consistent with Histiocytosis X. Subsequently, positive serological titers for Bartonella, a history of a cat-scratch antecedent to the onset of clinical symptoms and review of the original histopathology confirmed the diagnosis of cat-scratch disease. We reviewed the English language literature on osteolytic lesions associated with cat-scratch disease and compare the current case with those previously reported.

Adenocarcinoma in the lung in patients with breast cancer. A prospective analysis of the discriminatory value of immunohistology.

In some patients with a history of breast cancer who also have masses in the lung, making a clinical distinction between primary pulmonary neoplasia and pulmonary metastasis of mammary carcinoma may be impossible. To ascertain whether immunohistologic studies could contribute to resolving this problem, the authors undertook a prospective study of 30 cases showing synchronous or metachronous adenocarcinomas in these two sites. A predefined panel of antibodies--as derived from published antigenic catalogs for breast and lung cancer--was applied to each case. Tumors were interpreted as metastases if they were positive for gross cystic disease fluid protein-15, estrogen receptor protein, or S-100 protein. Conversely, primary adenocarcinomas of the lung were defined by their expression of carcinoembryonic antigen and a lack of the other three determinants. Using these criteria, 15 lesions were classified as metastatic; 11 were categorized as primary pulmonary adenocarcinomas; and 4 cases were indeterminate in origin. Responses to corresponding therapeutic protocols generally supported the validity of the immunohistologic diagnoses; 8 of 15 patients treated for metastatic breast cancer were well at least contact, as were 5 of 11 patients who received therapy for primary carcinoma of the lung. These data suggest that immunohistology plays a useful role in distinguishing mammary from pulmonary adenocarcinomas.

Large cell carcinoma of the lung with neuroendocrine differentiation. A comparison with large cell "undifferentiated" pulmonary tumors.

Twelve large cell carcinomas of the lung showing evidence of neuroendocrine differentiation (LCCND) were compared with 15 other large cell pulmonary tumors that lacked such features (NELCUC). All lesions were composed of partially necrotic, nested, or sheet-like arrays of mitotically active, nucleolated large cells that were at least twice the size of those seen in small cell carcinomas. Examples of LCCND were defined by immunoreactivity for neuron-specific enolase, Leu-7, synaptophysin, and chromogranin-A, and by their content of neurosecretory granules on electron microscopy. NELCUCs were devoid of these immunohistologic and ultrastructural features. There were six women and six men with LCCND, who ranged in age from 38 to 82 years. Of nine individuals in this group with Stage T1NOMO or T2NOMO disease at diagnosis, five (55%) died of their neoplasms within 3 years of diagnosis; three more (33%) have recurrent or persistent tumors and are likely to die as a result. On the other hand, 47% of patients with NELCUC of similar stages are free of disease after a similar follow-up period. LCCND is a distinctive clinicopathologic disease and should not be classified with unspecified large cell anaplastic carcinomas of the lung. Its behavior is potentially aggressive and may justify consideration of a specialized treatment protocol. Because electron microscopic evaluation of immunohistologic features must be done to recognize LCCND, it is probably underdiagnosed.

B-cell lymphoproliferative disorders in solid-organ transplant patients: detection of Epstein-Barr virus by in situ hybridization.

B-cell lymphoproliferative disorders (BLPDs) occur in approximately 2% of transplant recipients and are frequently fatal. Indirect serologic evidence has implicated Epstein-Barr virus (EBV) as an etiologic factor in these lesions. Direct evidence of the presence of EBV in these lesions has been obtained in relatively few cases. We used in situ hybridization (ISH) with a probe for the BamHI-W region of the EBV genome to study 52 tissue specimens from 28 solid-organ transplant patients who had BLPD. Epstein-Barr virus-infected lymphoid cells were identified in 26 of these 28 patients. The two patients without ISH evidence of EBV infection showed no distinctive clinical, morphologic, or serologic features. Previous filter-hybridization studies of these two patients had demonstrated evidence of EBV infection. Seven additional transplant patients without evidence of BLPD were studied as controls and showed no evidence of EBV in their lymphoid cells by ISH. These data provide further support for the etiologic role of EBV in the pathogenesis of posttransplantation lymphoproliferative disorders.