Efficacy of Low-dose (2 millicurie) versus Standard-dose (4 millicurie) Radioiodine Treatment for Cats with Mild-to-Moderate Hyperthyroidism.

BACKGROUND: Radioiodine (131 I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival. OBJECTIVE: To compare efficacy and short-term outcomes of low-dose 131 I versus higher, standard-dose 131 I as treatment for hyperthyroidism. ANIMALS: A total of 189 client-owned cats undergoing 131 I treatment for mild-to-moderate hyperthyroidism (serum T4 ≥ 4.0 µg/dL and <13.0 µg/dL). METHODS: Prospective, nonrandomized, cohort study comparing treatment with either low-dose (2 mCi, n = 150) or standard-dose (4 mCi, n = 39) 131 I. Serum T4 , thyroid-stimulating hormone (TSH), and creatinine concentrations were measured after 1, 3, and 6 months to determine persistent hyperthyroidism, overt hypothyroidism (low T4 , high TSH), subclinical hypothyroidism (normal T4 , high TSH), and azotemia. RESULTS: There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard- and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P = .0005) or subclinical (46% versus 21%; P = .004) hypothyroidism was more common in cats at 6 months after standard-dose 131 I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose 131 I had higher creatinine concentrations (P < .05) and higher percent rises in creatinine (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose 131 I is safe and effective for cats with mild-to-moderate hyperthyroidism, as evidenced by a cure rate of >95% with reduced frequency of iatrogenic hypothyroidism and azotemia.

Three-dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas.

Treatment protocols, treatment planning methods and tumour types in studies evaluating radiotherapy for canine brain tumours have been varied. This case series retrospectively evaluated the outcome of definitive, three-dimensional conformal radiation therapy (3D-CRT) as either a sole modality or as an adjuvant to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or cross-sectional imaging of the head (n = 21, assessed independently by two board certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy fractions. Median overall survival was 577 days (interquartile range = 272-829 days; range = 30-1942 days) when all deaths were considered and 906 days (interquartile range = 336-912 days; range = 10 -1942 days) when only dogs dying due to meningioma were considered. No significant difference in survival time was detected for the defined clinical or imaging findings or between treatment with radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D-CRT may be a viable alternative to surgery.

Chondroclasts are mature osteoclasts which are capable of cartilage matrix resorption.

Multinucleated cells termed chondroclasts have been observed on the deep surface of resorbed hyaline cartilage but the relationship of these cells to macrophages and osteoclasts and their role in rheumatoid arthritis (RA) and other arthritic conditions is uncertain. Multinucleated cells in RA and other arthritic conditions showing evidence of cartilage resorption were characterised immunohistochemically for expression of macrophage/osteoclast markers. Mature human osteoclasts formed from circulating monocytes and tissue macrophages were cultured for up to 4 days on slices of human cartilage and glycosaminoglycan (GAG) release was measured. Multinucleated cells resorbing unmineralised cartilage were seen in osteoarthritis, RA, septic arthritis, avascular necrosis and in four cases of giant cell tumour of bone that had extended through the subchondral bone plate. Chondroclasts expressed an osteoclast-like phenotype (TRAP+, cathepsin K+, MMP9+, CD14-, HLA-DR-, CD45+, CD51+ and CD68+). Both macrophages and osteoclasts cultured on cartilage released GAG. These findings indicate that chondroclasts have an osteoclast-like phenotype and that mature human osteoclasts are capable of cartilage matrix resorption. Resorption of unmineralised subchondral cartilage by chondroclasts and macrophages can be a feature of joint destruction in inflammatory and non-inflammatory arthropathies as well as inflammatory and neoplastic subchondral bone lesions.

Evaluation of complications and short-term outcome after unilateral or single-session bilateral tibial tuberosity advancement for cranial cruciate rupture in dogs.

OBJECTIVE: To compare the resulting complications, short-term results, and client satisfaction for treatment of cranial cruciate ligament rupture using either unilateral or bilateral single-session tibial tuberosity advancement (TTA) in dogs. METHODS: Medical records of 68 dogs (101 stifles) undergoing unilateral or bilateral single-session TTA were evaluated. Data gathered included signalment, history, physical examination findings, anaesthesia and surgical time, type of cranial cruciate ligament rupture and meniscal injury, implants, and intra-operative and postoperative complications. A mixed effect logistic regression analysis was performed to determine if complications were grouped by surgical procedure. Linear regression was performed to determine the influence of the variables on the occurrence of complications. Values of p <0.05 were considered significant. RESULTS: No major intra-operative complications occurred. Twenty stifles (20%) developed a complication after surgery (11 minor, 9 major). There was no significant difference in occurrence of complications between dogs undergoing unilateral (n = 8) or bilateral single-session (n = 12) TTA (p = 0.69). The only risk factor found to be associated with complication occurrence was age. CLINICAL SIGNIFICANCE: This is the first report evaluating the use of bilateral simultaneous TTA. There was no significant difference in complication rates between unilateral and bilateral single-session TTA. Additional evaluation is needed to fully determine the extent of complications and long-term outcome of bilateral single-session TTA.

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.

Immunopathogenesis of ovarian cancer.

Immune cells in the ovarian stromal microenvironment play an important role in ovarian tumorigenesis. Up-regulation of immune cell-derived mediators during ovulation may generate a proinflammatory niche, which may subsequently induce transformation of normal ovarian epithelial cells or endometriotic cells in the ovary. Once transformed ovarian epithelial cells develop, an immunoediting process occurs in which immune cells and their mediators dictate the development and progression of ovarian tumors. Tumor cells also develop several mechanisms to evade anti-tumor immunity by developing an immunosuppressive microenvironment. The differences in the population of immune cells infiltrating into ovarian tumor tissues are associated with differences in clinical outcomes. The underlying molecular mechanisms of the association begin to unravel with the development of microdissection techniques, high throughput technologies, in vitro functional assays, and in vivo mouse modeling. A better understanding of the complex relationship between ovarian tumor cells and the associated immune cells will allow us to develop novel immunologic strategies for ovarian cancer prevention and treatment.

Biaxial cell stimulation: A mechanical validation.

To analyse mechanotransduction resulting from tensile loading under defined conditions, various devices for in vitro cell stimulation have been developed. This work aimed to determine the strain distribution on the membrane of a commercially available device and its consistency with rising cycle numbers, as well as the amount of strain transferred to adherent cells. The strains and their behaviour within the stimulation device were determined using digital image correlation (DIC). The strain transferred to cells was measured on eGFP-transfected bone marrow-derived cells imaged with a fluorescence microscope. The analysis was performed by determining the coordinates of prominent positions on the cells, calculating vectors between the coordinates and their length changes with increasing applied tensile strain. The stimulation device was found to apply homogeneous (mean of standard deviations approx. 2% of mean strain) and reproducible strains in the central well area. However, on average, only half of the applied strain was transferred to the bone marrow-derived cells. Furthermore, the strain measured within the device increased significantly with an increasing number of cycles while the membrane's Young's modulus decreased, indicating permanent changes in the material during extended use. Thus, strain magnitudes do not match the system readout and results require careful interpretation, especially at high cycle numbers.

Heterobifunctional poly(ethylene oxide) oligomers containing carboxylic acids.

Syntheses of vinylsilyl alcohols having one to three vinyl moieties and their use as initiators for ethylene oxide polymerizations are discussed. Poly(ethylene oxide) oligomers with vinylsilanes at one end and a hydroxyl group at the other were prepared in base-catalyzed reactions. Molecular weights determined from 1H NMR and gel permeation chromatography were close to the targeted values. Carboxylic acid functional poly(ethylene oxide) oligomers were prepared from ene-thiol addition reactions of mercaptoacetic acid across the vinylsilane terminus. It is anticipated that these carboxylic acid functional oligomers will complex to magnetite nanoparticles to afford complexes that can be dispersed in aqueous media.

Bilateral correction of metatarsal rotation in a dog using circular external skeletal fixation.

An 8-month-old castrated male Saint Bernard was evaluated for bilateral hind limb lameness. Lameness was ascribed to bilateral metatarsal rotational abnormalities on the basis of the physical examination and radiographic evaluations. Staged, bilateral deformity correction and tarsometatarsal arthrodeses were performed using circular external skeletal fixators. The dog's gait improved following surgery and the fixators were removed 3 (left hind paw) and 4 (right hind paw) months following surgery. Twenty months after the initial surgery, the owner reported that the dog was walking well without apparent lameness. Previous reports suggest that metatarsal rotation is untreatable; however, our results suggest that surgical correction of this deformity can substantially improve limb function in dogs affected with metatarsal rotation.

Pericardial lipoma in a geriatric dog with an incidentally discovered thoracic mass.

An intrathoracic mass was discovered as an incidental finding in a 14-year-old, spayed, female Rottweiler cross during evaluation of urinary incontinence. Computed tomography suggested a pericardial or pleural location and high adipose content of the mass. The mass was removed via lateral thoracotomy with partial pericardectomy and was diagnosed as a pericardial lipoma. The dog recovered well, and there was no evidence of recurrence approximately one year later. Adipose tumours of the heart and its associated structures are rare in dogs and have been associated with both successful and fatal outcomes.

Angle stable locking reduces interfragmentary movements and promotes healing after unreamed nailing. Study of a displaced osteotomy model in sheep tibiae.

BACKGROUND: Large interfragmentary movements may delay bone-healing. The hypothesis of the present study was that a reduction of interfragmentary movements, especially of torsional rotation and bending angles, would support the healing process and lead to improved healing following unreamed tibial nailing. The objective of this study was to investigate healing of an unstable tibial osteotomy site following stabilization with unreamed nailing with a modified tibial device that had angle stable holes for the locking bolts. We compared those findings with healing after stabilization of such sites with standard unreamed tibial nailing. The duration of the study period was nine weeks. METHODS: The site of a standardized displaced osteotomy (3-mm gap) in twelve ovine tibiae was stabilized with unreamed tibial nailing: six animals were treated with a modified nail that had angle stable holes for the locking bolts, and six were treated with standard unreamed tibial nailing. In vivo gait analysis with optical measurements of interfragmentary movements and simultaneous measurements of ground reaction parameters were performed three days after the operation and once weekly afterward. After the animals were killed at nine weeks, the treated and contralateral tibiae were explanted, the implants were removed, and radiographs were made and evaluated for bridged cortices. Each pair of tibiae was also mechanically tested until torsional failure, after which the whole callus region was subjected to histological and histomorphometric analysis. RESULTS: Throughout the examination period, the interfragmentary movements in all directions were significantly smaller in the group treated with the angle stable tibial nail than they were in the group treated with standard unreamed tibial nailing. The limbs treated with the angle stable tibial nails returned to almost full weight-bearing during the period of the investigation, whereas those treated with standard nailing did not. Histomorphometric analysis, radiographic data, and mechanical testing showed superior bone-healing following treatment with the angle stable tibial nail. CONCLUSIONS: Use of an angle stable tibial nail may help to reduce interfragmentary movements in vivo and thus lead to superior bone-healing compared with that following standard unreamed tibial nailing.

Moment arms of the digital flexor tendons at the wrist: role of differential loading in stability of carpal tunnel tendons.

When a flexor digitorum superficialis tendon crossing a flexed or extended wrist has a load applied to it in excess of that applied to adjacent tendons, that tendon may translate across the carpal tunnel. In 6 cadaver specimens, each of the 9 carpal tunnel tendons was loaded with a baseline tension of 85 g and the moment arms of the flexor pollicis longus and the 4 flexor digitorum superficialis tendons were determined. Applying a higher 540-g load to individual flexor digitorum superficialis tendons and the flexor pollicis longus while loading the remaining tendons with the baseline 85-g tension significantly changed the moment arms from those measured under baseline load. The results demonstrated that tendons with applied differential loads in the carpal tunnel shift their positions, as revealed by their changing moment arms.

Cloning and genetic mapping of zebrafish BMP-2.

The BMP family of polypeptide growth factors has been shown to play diverse roles in establishing embryonic patterning and tissue fates. We report the cloning of the zebrafish homologue of BMP-2, examine its expression during embryogenesis, and find that it is localized to the distal end of the long arm of zebrafish chromosome 20. A missense mutation of the bmp2 gene has recently been shown to be responsible for the early dorsalized phenotype of the zebrafish swirl mutant [Kishimoto et al., 1997]. Given the dynamic expression of bmp2 in the developing embryo and the complex interactions of BMP signaling response in vertebrates, it is possible that other mutant phenotypes, due to altered bmp2 gene expression, will eventually map to or interact with this genetic locus.

The use of the arthroscope as an adjunct in the resection of a chondroblastoma of the femoral head.

We present a case of the use of an arthroscope as an adjunct in the resection of a tumor (chondroblastoma) of the femoral head. Use of the endoscope in this case allowed preservation of the femoral head and neck. Although the arthroscope has been used intraarticularly for the resection of tumors, to our knowledge it has not been used endosteally.

Cost-effectiveness of total joint arthroplasty in osteoarthritis.

Although total joint replacement (TJR) is a major advance in the treatment of patients with osteoarthritis, its cost-effectiveness has been questioned. We report the results of a study of the costs and benefits of TJR in consecutive osteoarthritis patients, 6 months after the surgery. Health status was measured by the Index of Well-Being. Costs of services for arthritis were determined by interview and billing records. Six months after TJR, significant improvements were seen in global health and in functional status. The average cost of care for the 6 months prior to TJR was $933. The average cost during the 6 months beginning with the TJR was $22,730 per patient--due almost entirely to costs of surgery. In general, the surgery did not change work status, probably because the mean age of the patients was 66.4 years. There were large effectiveness/cost differentials (the larger the effectiveness/cost differential, the higher the degree of cost-effectiveness [CE]). At 6 months, for all patients, the CE was associated with initial health status. The highest CE was observed in 10 patients who initially had the poorest health. TJR is more cost-effective for patients with the most to gain and less effective for those with better preoperative health status.

Quality assurance in eight adult medicine group practices.

Four evaluations of ambulatory medical care tasks were developed for use in quality assurance. The evaluations used medical records data and explicit criteria incorporating branching logic. They were implemented in eight general medicine provider groups in two teaching hospitals and six related health centers. Agreement with criteria among 316 provider responses to questionnaires varied from 57% to 100%. The percentage of cases with one or more variation from evaluation criteria, confirmed on peer review to have a deficiency in care, ranged by task from 6% to 42%, with substantial variation between sites. Physician reviewers from each site varied in leniency. Numbers of actions taken to correct deficiencies ranged by site and task from zero to six. Multisite evaluations revealed differences in performance and efforts to improve that are not apparent when each site conducts its own evaluations. More uniformly effective and impartial quality assurance is needed to correct some important deficiencies in care observed in this study.

Cost-effectiveness of screening for hypo- and hyperthyroidism in India.

The development of relatively inexpensive radioimmunoassay techniques opens new possibilities for widespread screening for hypo- and hyperthyroidism in developing regions where iodine deficiency is great. From component cost analysis, it appears that radioimmunoassays of thyroid hormones can be performed in India for as little as 2.4 rupees (29 cents) per test. Cost-effectiveness analysis indicates that screening for hypothyroidism in iodine-deficient areas in India is, of alternative detection strategies, the most cost-effective: Cases are found at an average cost of 40 rupees ($4.80) per case. Cost breakdowns and considerations of convenience and acceptability indicate that filter paper methods may soon be preferred to whole-blood assays, especially for screening. Cost-effectiveness findings for these screening strategies and for reasonable modifications of them should be compared with the estimated cost-effectiveness of iodine supplementation in determining optimal health policy toward subclinical thyroid disease.

The incidence and economic costs of cancer, motor vehicle injuries, coronary heart disease, and stroke: a comparative analysis.

The economic impact of disease and injury has most often been calculated by examining the costs associated with the prevalence of the impairments in the reference year. An alternative accounting approach is to assign all disease costs to the year of incidence, an approach which entails present-valuing to the year of incidence both health care expenditures and lost productivity. The incidence approach is the more appropriate for gauging the economic gains achievable through prevention, immediate rehabilitation, and arresting progression. Incidence-based costs have been estimated for the United States in 1975 for cancer, coronary heart disease, motor vehicle injuries, and stroke. A noteworthy finding is the relative economic importance of motor vehicle injuries, which frequently have been overlooked in the ordering of public health expenditure priorities. After cancer, which generated approximately $23.1 billion in present-valued costs in 1975 (discounted at 6 per cent), motor vehicle injuries and coronary heart disease constitute the next most expensive conditions--having generated estimated annual costs of $14.4 billion and $13.7 billion, respectively. Stroke, at $6.5 billion, follows in economic importance.