Treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 delivered from a fibrin matrix

OBJECTIVE: To report the results of the treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 (nglBMP-2) delivered from a designed fibrin matrix. STUDY DESIGN: Experimental trial in rodents and prospective clinical study in dogs and cats with nonunion fractures. ANIMALS: Twenty adult female, albino, Sprague-Dawley rats; 8 client-owned cats and dogs. METHODS: After development of a fibrin matrix and evaluation of nglBMP-2 in a rodent femoral defect model, 8 consecutive long bone nonunion fractures (no progression in healing in > or = 3 months), were treated using 300 microg nglBMP-2 in a liquid fibrin precursor, injected into the defect gap after fracture revision and stabilization, or through a stab incision into the fracture site. The fibrin matrix was designed to clot in the wound after 60 seconds and to release the nglBMP-2 continuously over several days. RESULTS: Using only fibrin gel, 7% of the rat femoral defect was filled with new formed bone compared with 79% defect filling using 2 microg nglBMP-2 (P=.006). Five and 10 microg nglBMP in fibrin resulted in union of all femoral defects with complete filling of the gap with new bone. Bony bridging and clinical healing was achieved in 7 patients within 24 weeks of administration of nglBMP-2. CONCLUSIONS: Application of nglBMP-2 in a functional matrix can induce bone healing. Controlled release of nglBMP-2 from a fibrin matrix mimics the natural fracture hematoma. CLINICAL RELEVANCE: nglBMP-2/fibrin can successfully replace a cancellous bone autograft in fracture treatment with an associated reduction in graft donor site morbidity and surgical time.     

Quantitative analysis of scintigraphic findings in tibial stress fractures in Thoroughbred racehorses

OBJECTIVE: To develop a quantitative method of interpreting tibial scintigrams of Thoroughbred racehorses with tibial stress fractures that may facilitate diagnosis of fractures and to provide prognostic information regarding future performance of affected horses. ANIMALS: 35 Thoroughbred racehorses. PROCEDURES: Static bone-phase scintigrams of tibial stress fractures were quantitatively analyzed by use of ratios of the mean radionuclide counts per pixel in a region of interest (ROI) drawn around the area of increased uptake of radiopharmaceutical to mean counts per pixel in a second ROI drawn around an apparently normal area of the tibial diaphysis. In horses with unilateral fractures, ratios for the contralateral tibia were determined by use of 2 ROIs drawn at the same positions as the ROIs in the fractured tibia. Ratios were compared between fractured versus apparently normal tibias, between horses that returned to racing versus those that did not, and among horses with various grades of lameness. The association between ratios for fractured tibias and intervals between diagnosis and return to racing was also assessed. RESULTS: Mean ratio of ROIs in apparently normal tibias was 1.35 (95% confidence interval [CI], 1.21 to 1.50); that in tibias with stress fractures was 3.55 (95% CI, 2.50 to 4.60). These ratios were significantly different. None of the associations between ratios for fractured tibias and grades of lameness or performance outcomes were significant. CONCLUSIONS AND CLINICAL RELEVANCE: Tibial stress fracture scintigrams can be quantitatively analyzed. A prospective study with a controlled rehabilitation period is necessary to evaluate the possible applications of this method.     

Shear wave elastography evaluation of cats with chronic kidney disease

Chronic kidney disease (CKD) is a major health condition in cats that can lead to poor quality of life and financial implications for therapy. Currently staging and identification of CKD is limited by diagnostic testing such as creatinine and urine-specific gravity, which do not change until late in the disease course. Other methods to evaluate CKD would be valuable in the clinical setting. Shear wave elastography is one novel ultrasound method, which has shown promise in identifying increases in tissue stiffness and identifying CKD in people. As CKD is often histologically characterized by tubulointerstitial fibrosis, shear wave elastography has the potential to identify CKD and differentiate between stages of CKD in cats. This prospective observational case-control study with 78 cats found no difference in shear wave velocities between groups (P = 0.33), a contradictory finding to one prior publication. There was no effect of weight (P = 0.65), nor the presence of mineralization (P = 0.31) or infarction (P = 0.52) on cortical shear wave velocities. There was a significant effect of age on shear wave velocity (P = 0.018) where velocities increased with age. The intraclass correlation coefficient was only moderate (0.62). Possible reasons for the difference in results between our work and that published prior, include differences in methodology and differences in instrumentation. Variability in measurements in our population may be due to the effects of respiratory motion or limitations in shear wave elastography software. As such, shear wave elastography is not currently recommended as a tool to evaluate CKD in cats and further work is necessary.     

MRI features can help to confirm a diagnosis of progressive myelomalacia,but may not be accurate in dogs lacking characteristic clinical signs at the time of imaging

Progressive myelomalacia (PMM) is a fatal sequela of acute thoracolumbar intervertebral disc extrusion in dogs, with unpredictable onset in the days after the inciting injury. No single reliable diagnostic test is currently available. Magnetic resonance imaging (MRI) features such as T2-weighted spinal cord hyperintensity and loss of subarachnoid signal in a half-Fourier single-shot turbo spin echo (HASTE) sequence have been associated with PMM, but are sometimes present in other dogs with severe deficits. Magnetic resonance imaging findings in 22 dogs with a clinical or histopathologic diagnosis of PMM and 38 deep pain-negative paraplegic dogs were compared in a retrospective case-control study. Length of T2-weighted hyperintense spinal cord change and HASTE signal loss were significantly associated with clinically evident PMM (P = .0019 and P = .0085), however, there were no significant differences between groups when analysis was restricted to dogs not yet showing clinical signs of PMM. The PMM group also had significantly shorter compressive lesions than the control group (P = 0.026), suggesting a possible role of more severe focal pressure at the extrusion site. A segment of total loss of contrast enhancement in the venous sinuses and meninges, a feature not previously described, was more common in the PMM group and the difference approached significance (P = 0.054). Findings show that MRI features can support the diagnosis in dogs with clinical evidence of PMM, and absence of these features supports absence of PMM at time of imaging. However, their absence does not reliably differentiate dogs with imminent progressive myelomalacia from other dogs with severe deficits following intervertebral disc extrusion.     

Post-fertilization physiology and growth performance of loblolly pine clones

The physiological processes leading to enhanced growth of loblolly pine (Pinus taeda L.) following fertilization are not clearly understood. Part of the debate revolves around the temporal response of net photosynthetic rate (A(n)) to fertilization and whether the A(n) response is always positive. We measured light-saturated photosynthetic rate (A(sat)), dark respiration rate, growth and crown silhouette area in eight clones of loblolly pine before and after nitrogen (N) fertilization (112 kg ha(-1)) to track the initial physiological changes prior to any changes in growth. Overall, there were positive photosynthetic and growth responses to fertilization; however, there were pronounced physiological and growth differences among clones, even among clones with the same parents. Clones 4, 6 and 7 showed large volume growth and A(sat) responses to fertilization. Clone 1 and Clone 8 (a full-sibling of Clone 7) mainly showed a volume growth response, whereas Clone 2 (full-sibling of Clone 1) showed an A(sat) response only. Clone 5 (full-sibling of Clone 6) showed little response to fertilization, whereas Clone 3 (full-sibling of Clone 4) showed a negative A(sat) response. Thus, within-family variation warrants further study to ensure that relatively expensive clonal material is used efficiently.     

Use of a urea breath test to evaluate short-term treatments for cats naturally infected with Helicobacter heilmannii.

OBJECTIVE: To evaluate efficacy of 3 short-term treatments in cats naturally infected with Helicobacter heilmannii. ANIMALS: 29 cats infected with H heilmannii that had positive results for a urea breath test, rapid urease test, and Helicobacter species-specific polymerase chain reaction test. PROCEDURES: Cats anesthetized for routine surgical procedures were randomly allocated to 4 groups: group 1, control cats; group 2, cats treated with azithromycin, tinidazole, ranitidine, and bismuth once daily for 4 days; group 3, cats treated with clarithromycin, metronidazole, ranitidine, and bismuth twice daily for 4 days; and group 4, cats treated with clarithromycin, metronidazole, ranitidine, and bismuth twice daily for 7 days. Efficacy was determined on the basis of results of a urea breath test performed 10 and 42 days after end of treatment. RESULTS: Ten days after treatment, 0 of 4, 4 of 6, 11 of 11, and 8 of 8 cats in groups 1 to 4, respectively, had a negative result for a urea breath test. Forty-two days after treatment, 0 of 4, 3 of 6, 7 of 11, and 4 of 8 cats in groups 1 to 4, respectively, still had a negative result. CONCLUSIONS AND CLINICAL RELEVANCE: Treatments used in this study regularly suppressed breath 13CO2 production. However, although 23 of 25 (92%) cats had negative results for a urea breath test 10 days after treatment, only 14 of 25 (56%) cats still had negative results 42 days after treatment. It is difficult to achieve a definitive long-term cure in cats naturally infected with H heilmannii.     

Assessment of cytotoxicity and AhR-mediated toxicity of sediments from water level fluctuation zone in the Three Gorges Reservoir,China

Purpose

The Three Gorges Dam project is one of the biggest projects in the world. The water level fluctuation zone (WLFZ) was created with impoundment. The purpose of the current study is to investigate the ecotoxicological potential of the sediment extracts from the WLFZ and propose future WLFZ monitoring for early detection of environmental changes brought about by pollution.

Materials and methods

The investigation was performed by using cell-based in vitro bioassays to determine acute cytotoxicity (neutral red retention assay) and mechanism-specific aryl hydrocarbon receptor (AhR)-mediated activity (7-ethoxyresorufin-O-deethylase (EROD) induction assay) of sediment extracts with rainbow trout (Oncorhynchus mykiss) liver cells (RTL-W1).

Results and discussion

Results showed that the cytotoxicity and AhR-mediated toxicity potential of the sediment extracts from the WLFZ in the Three Gorges Reservoir (TGR) were moderate of level compared with the ecotoxicity of sediments from other river systems. However, according to a sediment classification system in Germany, sediments from some individual sites in the WLFZ showed strong toxicity. Compared to the results from the Yangtze River in our previous study, more attention should be paid to the aryl hydrocarbon receptor inducers in the WLFZ in TGR.

Conclusions

The in vitro bioassays used in this study may serve as a valuable tool to predict the potential ecological hazards of the organic pollutants in the WLFZ to the aquatic organisms in some extent.

     

Prevalence of clinical and subclinical middle ear disease in cats undergoing computed tomographic scans of the head

Three hundred and ten cats that had CT imaging of the head between January 2000 and December 2007 were evaluated retrospectively. Data that were recorded included signalment, presenting complaint, clinical signs, presence of upper respiratory tract disease, and CT findings. One hundred and one cats had evidence of middle ear disease on CT. Thirty-four of the 101 cats (34%) did not have a primary complaint of ear-related disease, clinical signs or physical findings consistent with ear disease, suggesting that the middle ear disease was subclinical. Twenty-seven of the 34 cats (79%) had concurrent nasal disease. Middle ear lesions were chronic in appearance. With the exception of tympanic bulla lysis, CT findings were similar in cats presenting with primary aural disease versus cats with presumptive subclinical middle ear disease. The majority of the cats did not return for treatment of the identified middle ear abnormalities. Subclinical middle ear disease is relatively frequent in cats undergoing CT imaging of the head. Few cats required subsequent treatment for ear disease although follow up was limited. Identification of subclinical middle ear abnormalities on CT should prompt acquisition of a detailed patient history and bilateral otoscopic examination.