Fish response to the temporal hierarchy of the natural flow regime in the Daly River, northern Australia.

In this study, relationships between flow variation across multiple temporal scales and the distribution and abundance of three fish species, western rainbowfish Melanotaenia australis, sooty grunter Hephaestus fuliginosus and barramundi Lates calcarifer were examined at eight sampling reaches in the Daly River, Northern Territory, Australia. Discharge was highly seasonal during the study period of 2006-2010 with a distinct wet-dry discharge pattern. Significant catchment-wide correlations were identified between species abundance and hydrologic variables across several scales describing the magnitude and variability of flow. A Bayesian hierarchical model which accounted for >80% of variation in abundances for all species and age classes (i.e. juvenile and adult), identified the extent to which the influence of short-term flow variation was dependent upon the historical flow regime. There were distinct ontogenetic differences in these relationships for H. fuliginosus, with variability of recent flows having a negative effect on juveniles which was stronger at locations with higher historical mean daily flow. Lates calcarifer also displayed ontogenetic differences in relationships to flow variation with adults showing a positive association with increase in recent flows and juveniles showing a negative one. The effect of increased magnitude of wet-season flows on M. australis was negative in locations with lower historical mean daily flow but positive in locations with higher historical mean daily flow. The results highlighted how interactions between multiple scales of flow variability influence the abundance of fish species according to their life-history requirements.

Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse.

Infection with the human immunodeficiency virus (HIV) results in immunosuppression and depletion of circulating CD4+ T cells. Since the thymus is the primary organ in which T cells mature it is of interest to examine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocytes have been previously demonstrated to be susceptible to HIV infection both in vivo, using the SCID-hu mouse, and in vitro. The present study sought to determine which subsets of thymocytes were infected in the SCID-hu mouse model and to evaluate HIV-related alterations in the thymic microenvironment. Using two different primary HIV isolates, infection was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kinetics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infection. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells could not be definitively shown. Furthermore, degenerating TE cells were observed even without detection of HIV in the degenerating cells. Two striking morphologic patterns of infection were seen, involving either predominantly thymocyte infection and depletion, or TE cell involvement with detectable cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in the human thymus is susceptible to HIV infection, and infection with HIV results in a marked disruption of the thymic microenvironment leading to depletion of thymocytes and degeneration of TE cells.

Harvesting 48V at the National Superconducting Cyclotron Laboratory.

As part of an effort to develop aqueous isotope harvesting techniques at radioactive beam facilities, 48V and a cocktail of primary- and secondary-beam ions created by the fragmentation reaction of a 160 MeV/nucleon 58Ni beam were stopped in an aqueous target cell. After collection, 48V was separated from the mixture of beam ions using cation-exchange chromatography. The extraction efficiency from the aqueous solution was (47.0 ± 2.5)%, and the isolated 48V had a radiochemical purity of 95.8%. This proof-of-concept work shows that aqueous isotope harvesting could provide significant quantities of rare isotopes which are currently unavailable at conventional facilities.

Participation of tyrosine phosphorylation in the cytopathic effect of human immunodeficiency virus-1.

Protein tyrosine phosphorylation is a common mechanism of signaling in pathways that regulate T cell receptor-mediated cell activation, cell proliferation, and the cell cycle. Because human immunodeficiency virus (HIV) is though to affect normal cell signaling, tyrosine phosphorylation may be associated with HIV cytopathicity. In both HIV-infected cells and transfected cells that stably express HIV envelope glycoproteins undergoing HIVgp41-induced cell fusion, a 30-kilodalton protein was phosphorylated on tyrosine with kinetics similar to those of syncytium formation and cell death. When tyrosine phosphorylation was inhibited by the protein tyrosine kinase inhibitor herbimycin A, envelope-mediated syncytium formation was coordinately reduced. These studies show that specific intracellular signals, which apparently participate in cytopathicity, are generated by HIV and suggest strategies by which the fusion process might be interrupted.

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Recombination signal sequence binding protein Jkappa is constitutively bound to the NF-kappaB site of the interleukin-6 promoter and acts as a negative regulatory factor.

Analysis by electrophoretic mobility shift assays (EMSA) of the different proteins associated with the kappaB sequence of the interleukin-6 (IL-6) promoter (IL6-kappaB) allowed us to detect a specific complex formed with the recombination signal sequence binding protein Jkappa (RBP-Jkappa). Single-base exchanges within the oligonucleotide sequence defined the critical base pairs involved in the interaction between RBP-Jkappa and the IL6-kappaB motif. Binding analysis suggests that the amount of RBP-Jkappa protein present in the nucleus is severalfold higher than the total amount of inducible NF-kappaB complexes but that the latter bind DNA with a 10-fold-higher affinity. A reporter gene study was performed to determine the functional implication of this binding; we found that the constitutive occupancy of the IL6-kappaB site by the RBP-Jkappa protein was responsible for the low basal levels of IL-6 promoter activity in L929sA fibrosarcoma cells and that RBP-Jkappa partially blocked access of NF-kappaB complexes to the IL-6 promoter. We propose that such a mechanism could be involved in the constitutive repression of the IL-6 gene under normal physiological conditions.

Non-randomized, prospective, multi-centre evaluation of the ABSOLUTE .035 peripheral self-expanding stent system for occluded or stenotic superficial femoral or proximal popliteal arteries (ASSESS Trial): acute and 30-day results.

AIM: The aim of the paper was to investigate the performance of the ABSOLUTE .035 Peripheral Self-Expanding Stent System in preventing restenosis of superficial femoral or proximal popliteal arteries. Due to a lack of large controlled trials proving its long-term durability femoropopliteal artery stenting is still a matter of debate. In this paper we report the study design, the acute and short-term results of a prospective European registry on the treatment of TASC B and C femoropopliteal lesions with the use of the ABSOLUTE stent. METHODS: This prospective, non-randomized, multi-centre study enrolled 122 patients with symptomatic peripheral occlusive disease at 14 sites in Europe. Patients were included with obstructed femoropopliteal arteries. Key inclusion criteria were de novo lesions > or = 4.0 mm and < or = 7.0 mm in diameter, and > or = 40 mm and < or = 200 mm in length. Single target vessel treatment had to be performed with a maximum of three stents. RESULTS: Mean target lesion length was 108 +/- 44 mm (range 22.2 to 200 mm) and mean reference vessel diameter 4.6 +/- 0.8 mm by quantitative angiography; 71% of the lesions analyzable by quantitative angiography (QA) had total occlusions. A total of 227 stents were implanted, 224 of which were deployed successfully (98.7%). Mean percentage of diameter stenosis was reduced from 90.9 +/- 15.5 % (range 41.3 to 100) to 19.0 +/- 8.4% (range 2.3 to 41.5). Device and procedural success were 83.6% each whereas technical success reached 100%. Sixteen lesions had a > or = 30% residual stenosis post-procedure, 6 of them (37.5%) rated as being calcified. Eleven patients experienced major complications (9.1%) and 6 patients experienced minor complications (5%) within 30 days. Duplex ultrasound based 1-month restenosis rate was 9.3%. Target lesion revascularization (TLR) and target vessel revascularization (TVR) rates were 0.8% and 1.7%, respectively and amputation rate was 0.8%. Mean ankle-brachial index (ABI) at rest and after exercise increased significantly from baseline to 30 days follow-up by 0.63 +/- 0.20 to 0.94 +/- 0.17 and from 0.44 +/- 0.23 to 0.85 +/- 0.21, respectively (P<0.001 each). CONCLUSION: The treatment of TASC B and C femoro-popliteal lesions with use of the ABSOLUTE stent is safe and feasible. Short-term follow-up documents persistent improvement of hemodynamics. The 6- and 12-month data have to be awaited for further conclusions:

Sensitization of tumor cells to tumor necrosis factor action by the protein kinase inhibitor staurosporine.

Tumor necrosis factor (TNF), first described as a cytokine with tumor-necrotizing activity, is now known to be a pleiotropic molecule. The molecular mechanisms responsible for the cytotoxic activity of TNF on malignant cells are still largely unknown. In this study, we report that the protein kinase inhibitor staurosporine (56 to 1500 nM) increases about 500 times the in vitro cytotoxic activity of TNF for several murine and human tumor cell lines. Even some tumor cell lines which are resistant to TNF cytotoxicity could be sensitized to TNF killing by staurosporine. In the L929 fibrosarcoma cell line, staurosporine also enhanced the transcriptional activation of interleukin 6 synthesis by TNF (500-fold stimulation at 56 nM). At the biochemical level, staurosporine increased the TNF-mediated activation of phospholipases C and D and the transcription factor NF-kappa B in L929 cells. The TNF-sensitizing effect of staurosporine does not seem to be mediated by one of the currently known staurosporine-sensitive kinases, as various other inhibitors which also inhibit one or more of these kinases were not synergistic with TNF. Interestingly, staurosporine (1 microgram) also enhanced the in vivo antitumor activity of TNF against a murine tumor model (L929 fibrosarcoma) in athymic nude mice (Swiss-nu/nu; s.c. treatment). These results suggest that TNF responsiveness of tumor cells is regulated by a novel staurosporine-sensitive target and that the combination of TNF and staurosporine may open new strategies of tumor treatment.

A novel approach for BCR-ABL1 standardization to improve International Scale estimation.

INTRODUCTION: Standardization of BCR-ABL1 messenger RNA quantification by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged. In addition, several BCR-ABL1 IS quantification methods and secondary reference materials became commercially available. However, it was observed that different IS methods generate consistently different results. METHODS: To overcome these difficulties, we have developed an alternative and simple approach of CF calculation, based on the retrospective analysis of existing external quality assessment (EQA) data. Our approach does not depend on the exchange of samples and is solely based on the mathematical CF calculation using EQA results. RESULTS AND CONCLUSION: We have demonstrated by thorough statistical validation that this approach performs well in converting BCR-ABL1 measurements to improve IS estimation. In expectation of a true golden standard method for BCR-ABL1 IS quantification, the proposed method is a valuable alternative.

Activation of p42/p44 mitogen-activated protein kinases (MAPK) and p38 MAPK by tumor necrosis factor (TNF) is mediated through the death domain of the 55-kDa TNF receptor.

In the mouse fibrosarcoma cell line L929sA, tumor necrosis factor (TNF) stimulates activation of the stress-responsive p38 mitogen-activated protein kinase (MAPK), as well as the classical p42 and p44 MAPK. TNF signaling can be mediated by p55 or p75 TNF receptors. Here, we demonstrate that TNF-R55 is sufficient to activate p42/p44 MAPK and p38 MAPK. Moreover, by expressing different membrane-bound or purely cytoplasmic truncations of TNF-R55, we show that the intracellular death domain of TNF-R55 is the crucial domain involved. The cytoplasmic membrane-proximal region of TNF-R55, known to induce neutral sphingomyelinase activation, is not required for activation of p38 MAPK or p421p44 MAPK.

Intra-blood-brain barrier measles virus antibody synthesis in multiple sclerosis patients.

Antibodies to nine viruses were measured in serum and CSF of MS patients, patients with other neurologic diseases (OND), and healthy controls. The extent of antibody production inside the blood-brain barrier (BBB) was determined by making a new correction for BBB permeability. Compared with OND and healthy controls, MS patients as a group had significantly higher corrected CSF:serum antibody ratios for measles virus but not to the other eight viruses studied. The incidence of significantly high CSF:serum ratios for measles antibody in MS patients was 50%, and in the other two control groups it was 0 to 12%. The incidence of corrected antibody ratios to the other eight viruses was not significantly different among the three groups.

Possible beneficial effects of neutralizing antibodies and antibody-dependent, cell-mediated cytotoxicity in human immunodeficiency virus infection.

We studied the relationship between early human immunodeficiency virus type 1 (HIV-1) specific immune responses and pathogenesis of infection in participants enrolled in the multicenter AIDS cohort study (MACS). Sera collected at 6-month intervals for 2 years (visit 1-5) from 39 persons who seroconverted by enzyme-linked immunosorbent assay (ELISA) 6 months (visit 2) after enrollment were examined for isotype-specific Western blot reactivity, neutralizing antibodies (NA) against two divergent strains of HIV-1 (HIV-1IIIB and HIV-1RF), and for antibodies capable of participating in antibody-dependent, cell-mediated cytotoxicity (ADCC). These results were compared with changes in CD4+ cell number and episodes of lymphadenopathy. Twenty-five subjects had antibodies of at least one isotype reactive to at least one HIV-1 protein by Western blot at visit 1, before they became ELISA positive. NA reactive with HIV-1IIIB were detected before those reactive with HIV-1RF. NA were first observed in 11 sera at visit 2, in 22 sera at visit 3, and in 3 sera at visit 4; sera from three patients remained nonneutralizing through visit 5. In most cases, NA were detected after a decline in CD4+ cell numbers. The data are consistent with the interpretation that NA develop after about 16 to 18 months of declining CD4+ cell numbers, following which the rate of decline in CD4+ cell numbers slows. In contrast, HIV-1 envelope antigen-specific ADCC responses were first observed in 11 subjects at visit 1 when all 39 were NA and ELISA negative, in 12 subjects at visit 2, in 13 subjects at visit 3, and 1 subject at visit 4. Early ADCC responses were associated with high mean % CD4+ cell numbers and absence of lymphadenopathy throughout the 2-year observation period. Not all subjects who developed ADCC developed NA. In some subjects, ADCC and NA were detectable for the first time at the same visit, for others ADCC was detectable prior to NA, and for a few NA was detectable prior to ADCC. These findings suggest that ADCC and neutralization are mediated by different antibody populations, that they may partially inhibit the progress of HIV-1 infection, and that the late appearance of NA may relate to the failure of immunity to effect recovery from this infection.

Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6.

Interleukin (IL)-6 is a multifunctional cytokine that can be induced by a plethora of chemical or physiological compounds, including the inflammatory cytokines tumor necrosis factor (TNF) and IL-1. The molecule TNF has a trimeric configuration and thus binds to membrane-bound, cellular receptors to initiate cell death mechanisms and signaling pathways leading to gene induction. Previously, we showed that induced clustering of the intracellular domains of the p55 TNF receptor, or of their respective 'death domains' only, is sufficient to activate the nuclear factor kappa B (NF-kappa B) and several mitogen-activated protein kinase (MAPK) pathways. NF-kappa B is the exclusive transcription factor for induction of the IL-6 gene in response to TNF and functions as the final trigger to activate a multiprotein complex, a so-called 'enhanceosome', at the level of the IL-6 promoter. Furthermore, the enhanceosome displays histone acetylation activity, which turned out to be essential for IL-6 gene activation via NF-kappa B. However, activation of NF-kappa B alone is not sufficient for IL-6 gene induction in response to TNF, as inhibition of the coactivated extracellular signal-regulated kinase and p38 MAPK pathways blocks TNF-mediated gene expression. Nevertheless, the transactivating NF-kappa B subunit p65 is not a direct target of MAPK phosphorylation. Thus, we postulated that other components of the enhanceosome complex are sensitive to MAPK cascades and found that MAPK activity is unequivocally linked to the histone acetylation capacity of the enhanceosome to stimulate gene expression in response to TNF. In contrast, glucocorticoid repression of TNF-driven IL-6 gene expression does not depend on abrogation of histone acetyltransferase activity, but originates from interference of the liganded glucocorticoid receptor with the contacts between NF-kappa B p65 and the promoter configuration around the TATA box.

TNF-induced intracellular signaling leading to gene induction or to cytotoxicity by necrosis or by apoptosis.

TNF-induced apoptosis, e.g. in murine PC60 cells, requires the TNF receptor p55 (TNF-R55) and the TNF receptor p75 (TNF-R75); the latter even does not have to be triggered. The intracellular domain of TNF-R55 can be activated in the cytosol by linking it to the trimeric CAT protein; induction of this fusion protein leads to a full TNF response. A new MAP kinase, p38, has been shown to be also activated by TNF. This activation is essential for gene induction, but not for cytotoxicity in L929 cells. TNF treatment of L929 leads to reactive oxygen formation in the mitochondria, resulting in cell death by necrosis. TNF treatment of many other cell types results in apoptosis, and this process involves activation of one or more ICE homologs (IHO). In the mouse, seven cysteine proteases of the IHO family have been cloned and partially characterized. One or more of these IHOs is involved in cell killing by proteolysis of critical substrate(s). One substrate, which may be a key effector molecule in the apoptotic process, is PITSLRE kinase.

Conventional and enhanced plaque neutralization assay for polio antibody.

HEp-2 cells were more suitable as a cell substrate than Vero cells for plaque assay of wild or attenuated strains of poliovirus. Polio antibody titration by plaque neutralization was on the average 3.4 to 4.8 times more sensitive than antibody titration by virus CPE assay. The most pronounced effect on virus neutralization was achieved by extending the time of serum-virus interaction. Incubating the virus-antiserum mixture for 20 h instead of 1 h at 36 degrees C increased antibody titer to all three poliovirus types about 11- to 28-fold. Potentiation of poliovirus neutralization by heterologous antiglobulin was considerably less effective than with other virus-antibody systems. The virus plaque neutralization technique described should be capable of measuring minute amounts of antibody as required in special circumstances.

Ethanol modulates cocaine-induced behavioral change in inbred mice.

We recently conducted a study of the behavioral effects of combined cocaine and ethanol in genetically defined mice. Male and female C57BL/6 (B6) and DBA/2 (D2) were tested in an automated activity monitor on 2 consecutive days. On day 1, all animals received an IP injection of sterile saline and were placed into the activity monitor for 30 min. Behaviors measured were total distance traveled, stereotypy, nosepokes, and wall-seeking. On day 2, all animals were tested again for 15 min following injection of one of the following: saline, 10% v/v ethanol at 2.0 g kg(-1) or 2.0 g kg(-1) ethanol plus 5, 15, or 30 mg kg(-1) cocaine. Cocaine alone at the same doses was injected into separate groups of animals. For the B6 strain, the overall effect of ethanol was to reduce cocaine-induced locomotor stimulation; no consistent effect of ethanol on cocaine-induced locomotion was observed in D2 mice. Cocaine-induced inhibition of nosepokes in both strains and sexes was partially reversed by ethanol. Ethanol also partially reversed cocaine-elevated stereotypy in both strains and both sexes. In B6 mice, cocaine-increased wall seeking tended to be reversed by coadministration of ethanol, whereas no consistent pattern was observed in the D2s. Results from this study suggest that the several measures affected by cocaine (locomotor activity, stereotypy, exploration, thigmotaxis) were, in turn, differentially affected by concurrent treatment with ethanol. Furthermore, our results point to genetic-based differences in ethanol's effects on cocaine-related behaviors. We address the implications for combined ethanol and cocaine use in humans.

Sex and strain influence the effect of ethanol on central monoamines.

OBJECTIVE: We recently investigated the effects of EtOH on the mesolimbic dopamine and serotonin systems in male and female C57BL/6 (B6) and DBA/2J (D2) mice. METHOD: Male and female rodents from the B6 and D2 mouse strains (n = 11 per strain, sex and dose) were used in this study. Doses of EtOH (vs saline) administered were 1.0, 2.0 or 3.0 g/kg. RESULTS: Treatment with saline or EtOH produced both strain- and sex-dependent differences in patterns of monoamine response. For example, D2s exhibited significantly higher overall dopamine (DA) levels than did B6s in the frontal cortex (FC), nucleus accumbens (NA) and caudate-putamen (CP). In the FC, female D2 evinced elevated 5HIAA at 1.0 g/kg. In the NA, D2 females showed dose related increases in levels of DA up to 3.0 g/kg, whereas in the D2 males and in B6 males and females we observed no response. Also in the NA, B6 males showed increases in dihydroxyphenyacetic acid (DOPAC) at 1.0 and 3.0 g/kg. In the CP, B6 males showed higher DA levels than B6 females at the saline, and all EtOH doses. For serotoninergic activity in the CP as well as the NA, EtOH produced a distinctive triphasic response, with the 1.0 and 3.0 g/kg doses of EtOH producing higher levels than saline and 2.0 g/kg of 5HIAA in B6 males than in B6 females. CONCLUSIONS: Our findings indicate strain and sex differences in monoamine response to acute doses of ethanol, and further implicate (via changes in DOPAC) presynaptic mechanisms in the effects of ethanol on dopamine.

Live birth of a bear cub following nonsurgical embryo collection.

In the near future, 6 of 8 bear species will face extinction mainly because of loss of their natural habitat. This loss of habitat will ultimately require some of these bears to be maintained in zoos and wildlife preserves in the hope of conserving genetic diversity. If the giant panda is representative of other bear species, reproductive performance will be inhibited in such an environment. In this study, we used the nonendangered American black bear (Ursus americanus) as the model for developing appropriate embryo transfer procedures. The donor bear mated numerous times between late May and early June. In late July we anesthetized her and used a series of telescoping sheaths to gain access to the uterus Then we passed a catheter through the largest sheath, inflated the balloon, and, using a 20-mL syringe, repeatedly infused into and then aspirated from the uterus PBS + BSA. We emptied the syringe into Petri dishes and observed 2 embryos. We rinsed the embryos, placed them in human tubal fluid + HSA + HEPES and then held them at 35 degrees C for 5 h. The recipient mated during mid-June; in late July we anesthetized her and, with the aid of laparoscopy, transferred an embryo into the cranial portion of the uterine horn ipsilateral to the ovary containing a CL. The recipient delivered 2 cubs in January. Necropsy results indicated that the neonates lived for 6 to 8 wk before succumbing to flooding in the den. The DNA from hair samples belonging to the neonates indicated that the male cub belonged to the donor, the female cub to the recipient. The delayed implantation mechanism in bears probably allowed for the successful development of the embryo in the presence of a substantial asynchrony between the donor and the recipient (13 d). We conclude that embryo transfer is possible in the American black bear and can lead to the birth of live cubs.

Distal tibial fractures in dogs and cats.

A total of 43 fractures of the distal tibia in dogs and cats were evaluated for fracture patterns, methods of stabilization, and time to bone union. Fractures of the metaphysis (9.3%), physis (30.9%), epiphysis (2.3%), and malleoli (58.2%) were classified. Open reduction and internal fixation, with combinations of Kirschner wire, orthopedic wire, and bone screws, were the methods of fixation used in the majority of fractures. These relatively simple methods of fixation were applied to all sizes of dogs and cats and resulted in an average bone healing time of 6 weeks.

Fractures of the tibial diaphysis in dogs and cats.

One hundred ninety-five fractures of the canine and feline tibial diaphysis were reviewed. Signalment of the animal; cause, location, and description of the fracture; treatment of the fracture, and response of the fracture to treatment were evaluated. Spiral and oblique fracture patterns were the most frequent in both juvenile (animals less than 12 months old) and adult animals (animals more than 12 months old). Comminuted fractures and open fractures were seen more commonly in the adult animal. Closed reduction and external coaptation as a method of repair was used more frequently in juveniles and open reduction and internal fixation was used more frequently in adults. When open reduction and internal fixation was used, pins, wires, and Kirschner Ehmer external splints were used more frequently in juveniles, and plate and screw fixation of the fracture was used more frequently in adults. The time to bone union varied with age of the animal and method of fixation. Healing times increased in adults, and increased as the stability of the fracture fixation increased. Complications included osteomyelitis and nonunions. Nonunions developed in 4.1% of the fractures not lost to follow-up.