Long-term outcomes of thigh circumference, stifle range-of-motion, and lameness after unilateral tibial plateau levelling osteotomy.

Our study evaluated thigh circumference (TC), stifle range of motion (ROM), and lameness in dogs one to five years after unilateral tibial plateau levelling osteotomy (TPLO). We hypothesised that TC, stifle ROM, and lameness would not be different to the unoperated limb (control), one to five years after surgery. Patients that were one to five years post-TPLO were reviewed and were included if they had a unilateral TPLO, and no additional clinical evidence of orthopaedic disease. Standing mid-thigh TC measurements and stifle extension and flexion angles were made in triplicate. Clinical lameness was graded blindly. Data were evaluated statistically using paired t-tests for TC and stifle flexion and extension. Significance was set at p <0.05. Twenty-nine dogs met the inclusion criteria. Mean results for the surgery limbs and control limbs were 39.5 +/- 5.5 cm and 40.1 +/- 5.6 cm for TC, 36.6 +/- 6.8 degrees and 28.6 +/- 4.3 degrees for stifle flexion, and 155.2 +/- 6.6 degrees and 159.8 +/- 4.9 degrees for stifle extension, respectively. The mean TC for the operated limb was 98.5% of the control limb. A significant difference was found between the operated and the control limbs for all measurements. Time after surgery had no apparent affect on outcome. Four of 29 dogs (14%) exhibited some lameness in the TLPO limb during evaluation (one dog was 1 to 2 years postoperative and three dogs were 2 to 3 years postoperative). These results indicate that TC and stifle ROM in the TLPO limb do not return to control-limb measurements one to five years after a TPLO surgery. The clinical significance is unknown as TC returned to 98.5% of control, and the source of lameness in the lame dogs was not identified.

Computed tomographic evaluation of the canine intercondylar notch in normal and cruciate deficient stifles.

In the human and veterinary orthopaedic literature it has been implied that intercondylar notch stenosis is a mechanical factor in cranial cruciate ligament rupture and intraarticular graft failure. The patients in this study were classified as normal (32), unilateral cruciate rupture (23), or bilateral cruciate rupture (17). The dogs were placed under general anaesthesia and both stifles were scanned via computed tomography (CT) as previously described. Three CT slices at predetermined levels were evaluated within the notch. Measurements included opening notch angle, notch width and height, condyle width, and notch width index (notch width/condyle width) at two different heights within the notch. Intercondylar notch measurements at the most cranial extent were significantly more narrow in unilateral and bilaterally affected stifles when compared to the normal population. Significant differences were noted in the opening notch angle (ONA), notch width index (NWI), NWI at two thirds notch height (NWI2/3), and tibial slope index (TSI). No significant differences were noted between unilateral and bilateral affected stifles. Increased mechanical contact of the cranial cruciate ligament with a stenotic intercondylar notch may predispose the ligament to mechanical wear and structural weakening. Intercondylar notch measurements have been used as a tool to predict the risk of anterior cruciate ligament injury in young human athletes, and to assess the risk factors for intra-articular graft replacements. Our findings may be useful in developing similar predictive models using stifle CT scans.

The effect of computed tomographical gantry angle on the measurement of the canine intercondylar notch.

This study was conducted to evaluate the clinical application of computed tomography of the canine femoral intercondylar notch. The canine femoral intercondylar notch is angled 12 degrees from the dorsal plane and obliqued 7 degrees proximolateral to distomedial in the sagittal plane. Measurements of the notch were performed with eight, 12, and 16 degrees of gantry tilt. With the exception of proximal opening notch angle, significant differences were not detected in measurements referenced to 12 degrees of gantry tilt. Evidence from this study indicated that a +/- 4 degree variation in gantry tilt angle from a desired angle of 12 degrees did not significantly affect clinical interpretations of intercondylar notch measurements or notch width index ratios.

High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells.

Cells exposed to high ambient glucose concentrations are subject to increases in intracellular calcium ([Ca(2+)](i)). We therefore considered it likely that the calcium-dependent cysteine protease calpain would play a role in the development of high glucose-induced cell injury. After 3 and 24 h, high glucose concentrations (25 mM D-glucose) produced almost identical increases in the degree of necrotic cell death in kidney proximal tubular epithelial cells (LLC-PK(1)) compared to cells treated with control glucose (5 mM D-glucose). Necrotic cell death could be restricted by inhibiting the activity of calpain. High glucose-treated LLC-PK(1) cells were found to have significantly elevated [Ca(2+)](i) concentrations within 1 h, and elevated calpain activity within 2 h compared to control treated cells. The DNA nick sensor poly(ADP-ribose) polymerase (PARP) has previously been shown to be an important driver of high glucose-induced cell death, but here we found that although PARP activity was increased after 24 h, it was unaltered after 3 h. Furthermore, PARP inhibition with PJ-34 did not restrict early high glucose-induced necrosis. Using a gene knockdown strategy with small interference RNA, we found that silencing calpain was effective in reducing the degree of early high glucose-induced necrosis. We conclude that high glucose concentrations evoke an early, calpain-mediated necrosis in cultured proximal tubular cells that is PARP-independent, and precedes the previously recognized activation of apoptosis.

Outcome and prognostic factors in non-ambulatory Hansen Type I intervertebral disc extrusions: 308 cases.

Thoracolumbar intervertebral disc disease is the most common cause of caudal paresis in dogs. Whilst the pathogenesis of the extrusion has been widely studied, treatment protocols and prognostic factors relating to outcome remain controversial. Recent studies have examined a multitude of factors relating to time to regain ambulation after decompressive surgery. Most intervertebral disc herniations occur in the thoracolumbar region, causing upper motor neuron signs in the rear limbs, which are thought to have a more favourable prognosis compared to the lower motor neuron signs created by herniation of an intervertebral disc in the caudal lumbar region. Due to the potential disruption of the lumbar intumescence, lower motor neuron signs have been reported as having a less favourable prognosis. The purpose of this study was to evaluate the intervertebral disc space as a prognostic factor relating to ambulatory outcome and time to ambulation after decompressive surgery. Hansen Type I intervertebral disc extrusions were studied in 308 non-ambulatory dogs. Preoperative and postoperative neurological status, corticosteroid use, signalment, intervertebral disc space, postoperative physical rehabilitation, previous hemilaminectomy surgery, disc fenestration, return to ambulation, and time to ambulation were reviewed.

Comparison of radiographic arthritic changes associated with two variations of tibial plateau leveling osteotomy.

Osteoarthritis (OA) progresses in the canine cranial cruciate ligament (CCL) deficient stifle. Progression of OA is also documented in canine patients after various surgical repair techniques for this injury. We evaluated the radiographic arthritic changes in canine stifle joints that have sustained a CCL injury, and compared radiographic OA scores between Tibial Plateau Leveling Osteotomy (TPLO)surgery patients receiving a medial parapatellar exploratory arthrotomy for CCL remnant removal versus those receiving a limited caudal medial arthrotomy without removal of the CCL remnants. Medial/lateral and caudal/cranial stifle radiographs were obtained before surgery, immediately following TPLO surgery and at 7-38 months (mean 20.5) after surgery. Sixty-eight patients (72 stifles) were included in the study. The cases were divided into two groups. The patients in group 1 (n = 49 patients, 51 stifles) had a limited caudal medial arthrotomy, and patients in group 2 (n = 19 patients, 21 stifles) had a medial parapatellar open arthrotomy. A previously described radiographic osteoarthritis scoring system was used to quantify changes in both of the groups. The age, weight, OA scores, initial tibial plateau angle, final tibial plateau angle, and the change in angle were compared between the groups. The results showed that there was significantly less progression of OA in the group that had the limited caudal medial, arthrotomy, versus a medial parapatellar open arthrotomy. There was a significant advancement of the OA scores of patients that had TPLO surgery.

Autistic disorder versus other pervasive developmental disorders in young children: same or different?

Eighteen preschool children diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised (DSM III-R) as having Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) were compared to 176 children with DSM III-R Autistic Disorder (AD), and to 311 non-autistic children with developmental language disorders (DLD) (N = 201) or low IQ (N = 110). All children were partitioned into "high" and "low" cognitive subgroups at a nonverbal IQ of 80. Within cognitive subgroups, the 18 PDD-NOS children did not differ significantly from either the DLD or the AD children in verbal and adaptive skills and obtained scores intermediate between those of these groups. The PDD-NOS did not differ from the AD children in maladaptive behaviors. Both the PDD-NOS and AD children had many more of these behaviors than the non-autistic comparison groups. Children in the "high" and "low" cognitive subgroups of AD, but not of PDD-NOS, differed substantially on most measures, with the children with lower cognitive scores significantly more impaired on all measures. Similarity of PDD-NOS children to AD children in maladaptive behaviors and an intermediate position between autistic and non-autistic groups on virtually all measures explains the difficulty clinicians encounter in classifying children with PDD and raises questions about the specificity of these diagnostic subtypes of the autistic spectrum.

What is the best proton energy for accelerator-based BNCT using the 7Li(p,n)7Be reaction?

With a growing interest in the use of accelerator-based epithermal neutron sources for BNCT programs, in particular those based upon the 7Li(p,n)7Be reaction, there is a need to address the question of "what is the best proton energy to use?" This paper considers this question by using radiation transport calculations to investigate a range of proton energies from 2.15 to 3.5 MeV and a range of moderator sizes. This study has moved away completely from the use of empty therapy beam parameters and instead defines the beam quality and optimizes the moderator design using widely accepted in-phantom treatment planning figures of merit. It is concluded that up to a proton energy of about 2.8 MeV there is no observed variation in the achievable therapy beam quality, but a price is paid in terms of treatment time for not choosing the upper limit of this range. For higher proton energies, the beam quality falls, but with no improvement in treatment time for optimum configurations.

Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-gamma and TNF-alpha.

BACKGROUND: There is evidence for the role of inflammatory cytokines in the inhibition of erythropoiesis in the anemia of chronic disease, but the extent to which they contribute to resistance to erythropoietin (EPO) in patients with chronic renal failure is not clear. The purpose of the present study was to assess the effect of sera from patients with end-stage renal failure with and without infection or inflammatory disease on CFU-E colony formation in vitro. METHODS: Bone marrow was obtained from uremic patients with inflammatory disease and from healthy controls. Standard colony assays were used to assess erythroid colony formation (CFU-E) in response to EPO in the presence or absence of 5% autologous serum. Normal bone marrow mononuclear cells were cultured with 5% v/v sera from three groups of patients: healthy volunteers, uremic controls, and uremic patients with inflammatory disease. RESULTS: There was no difference between normal and uremic bone marrow response to EPO. However, when uremic/inflammatory bone marrow was cultured with autologous serum the optimal response to EPO was significantly inhibited. Optimal CFU-E colony formation was suppressed significantly by sera from either uremic group when compared with cultures containing sera from controls. Treatment of parallel cultures with a combination of antibodies to interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) almost completely restored the response to EPO. Additionally, bone marrow from healthy controls incubated with uremic sera showed an increased production of interleukin-1 alpha (IL-1 alpha) and IFN-gamma, and TNF-alpha was present in uremic sera. CONCLUSIONS: CFU-E colony formation is inhibited by soluble factors present in the sera of uremic patients with or without inflammatory disease. These soluble factors stimulate the production of IFN-gamma and TNF-alpha, which directly inhibit erythropoiesis at a local level in the bone marrow.

A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation.

OBJECTIVES: This study was done to test the hypothesis that a forced diuresis with maintenance of intravascular volume after contrast exposure would reduce the rate of contrast-induced renal injury. BACKGROUND: We have previously shown a graded relationship with the degree of postprocedure renal failure and the probability of in-hospital death in patients undergoing percutaneous coronary intervention. Earlier studies of singular prevention strategies (atrial natriuretic factor, loop diuretics, dopamine, mannitol) have shown no clear benefit across a spectrum of patients at risk. METHODS: A prospective, randomized, controlled, single-blind trial was conducted where 98 participants were randomized to forced diuresis with intravenous crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55). RESULTS: The groups were similar with respect to baseline serum creatinine (2.44+/-0.80 and 2.55+/-0.91 mg/dl), age, weight, diabetic status, left ventricular function, degree of prehydration, contrast volume and ionicity, and extent of peripheral vascular disease. The forced diuresis resulted in higher urine flow rate (163.26+/-54.47 vs. 122.57+/-54.27 ml/h) over the 24 h after contrast exposure (p = 0.001). Two participants in the experimental arm versus five in the control arm required dialysis, with all seven cases having measured flow rates <145 ml/h in the 24 h after the procedure. The mean individual change in serum creatinine at 48 h, the primary end point, was 0.48+/-0.86 versus 0.51+/-0.87, in the experimental and control arms, respectively, p = 0.87. There were no differences in the rates of renal failure across six definitions of renal failure by intent-to-treat analysis. However, in all participants combined, the rise in serum creatinine was related to the degree of induced diuresis after controlling for baseline renal function, r = -0.36, p = 0.005. The rates of renal failure in those with urine flow rates greater than 150 ml/h in the postprocedure period were significantly lower, 8/37 (21.6%) versus 28/61 (45.9%), p = 0.03. CONCLUSIONS: Forced diuresis with intravenous crystalloid, furosemide, and mannitol if hemodynamics permit, beginning at the start of angiography provides a modest benefit against contrast-induced nephropathy provided a high urine flow rate can be achieved.

Design for an accelerator-based orthogonal epithermal neutron beam for boron neutron capture therapy.

This paper is concerned with the proposed Birmingham accelerator-based epithermal neutron beam for boron neutron capture therapy (BNCT). In particular, the option of producing a therapy beam at an orthogonal direction to the incoming protons is considered. Monte Carlo radiation transport simulations, both with and without a head phantom, have shown that an orthogonal beam geometry is not only acceptable but is indeed beneficial, in terms of a lower mean neutron energy and an enhanced therapeutic ratio for the same useful neutron fluence in the therapy beam. Typical treatment times for various beam options have been calculated, and range from 20 to 48 min with a 5 mA beam of 2.8 MeV protons, if the maximum photon-equivalent dose delivered to healthy tissue is to be 12.6 Gy Eq. The effects of proton beam diameter upon the therapy beam parameters have also been considered.

Toward a final design for the Birmingham boron neutron capture therapy neutron beam.

This paper is concerned with the proposed Birmingham accelerator-based epithermal neutron beam for boron neutron capture therapy (BNCT). Details of the final moderator design, such as beam delimiter, shield, and beam exit surface shape are considered. Monte Carlo radiation transport simulations with a head and body phantom have shown that a simple flat moderator beam exit surface is preferable to the previously envisioned spherical design. Dose rates to individual body organs during treatment have been calculated using a standard MIRD phantom. We have shown that a simple polyethylene shield, doped with natural lithium, is sufficient to provide adequate protection to the rest of the body during head irradiations. The effect upon the head phantom dose distributions of the use of such a shield to delimit the therapy beam has been evaluated.

In-phantom neutron fluence measurements in the orthogonal Birmingham boron neutron capture therapy beam.

This paper presents the results of an experimental investigation into the performance of the Birmingham accelerator-based epithermal BNCT beam. In-phantom gold foil activation and boron trifluoride tube measurements have been used. The results have been compared with calculated response rates using Monte Carlo modeling of the entire neutron system from source to phantom and detector. The excellent agreement obtained gives us confidence in the validity of the simulations and our ability to predict accurately the neutronic performance of our BNCT facility.

Gracilis or semitendinosus myopathy in 18 dogs.

The clinical findings in 18 dogs with gracilis (n = 17) or semitendinosus (n = 1) myopathy are described. Each dog had a similar hind-limb gait abnormality characterized by a shortened stride with a rapid, elastic medial rotation of the paw, internal rotation of the hock and external rotation of the calcaneus [corrected] and internal rotation of the stifle during the mid-to-late swing phase of the stride. Medical management prior to or in lieu of surgery was attempted (n = 8) with no apparent response. Fifteen dogs had one or multiple surgical procedures. Although transection, partial excision, or complete resection of the affected muscle resulted in resolution of lameness following surgery, lameness recurred six weeks to five months (mean, 2.5 months; median, two months) following surgery. Adjunctive medical treatment did not prevent recurrence. Variable replacement of the affected muscle with fibrous connective tissue (predominantly along the caudolateral border of the muscle) was evident grossly, and replacement of myofibers with fibrous connective tissue was confirmed histologically. A definitive etiology could not be established.

Evaluation of a hypertonic saline-dextran solution for treatment of dogs with shock induced by gastric dilatation-volvulus.

OBJECTIVE: To test the hypothesis that small volumes of hypertonic saline-dextran (HSD) solution can be used to effectively resuscitate dogs in shock induced by gastric dilatation-volvulus (GDV), and, compared with administration of large volumes of lactated Ringer's solution (LRS), can be used to limit the overall volume of fluid needed for resuscitation. DESIGN: Prospective, clinical study. ANIMALS: 15 dogs with GDV-induced shock. PROCEDURE: Initially, HSD solution (5 ml/kg of body weight) or LRS (60 to 90 ml/kg) was administered. All dogs then received a maintenance administration (20 ml/kg/h) of LRS. Cardiorespiratory, blood gas, and serum biochemical analyses were performed over a 4-hour period after initiation of treatment. RESULTS: Systolic arterial and central venous pressures and plasma volume increased more rapidly in dogs in the HSD + LRS group. The cumulative dose of fluids administered to dogs in the HSD + LRS group was significantly less than that administered to dogs in the LRS group. Serum sodium and chloride concentrations and osmolality increased significantly in dogs in the HSD + LRS group, but not in dogs in the LRS group. Ventricular arrhythmias were detected in both groups of dogs, but did not appear to be induced by either form of fluid therapy. CLINICAL IMPLICATIONS: Administration of HSD rapidly restored cardiorespiratory function and induced resuscitation equivalent to administration of large volumes of LRS. Use of HSD solutions to treat dogs in GDV-induced shock may be more efficient than use of isotonic fluids. Administration of HSD solution was not associated with noticeable complications.

Factors associated with perioperative mortality in dogs with surgically managed gastric dilatation-volvulus: 137 cases (1988-1993).

OBJECTIVE: To evaluate factors associated with perioperative mortality in dogs with gastric dilatation-volvulus and to determine the influence of treatment differences between university and private specialty practices on outcome. DESIGN: Retrospective analysis of medical records. ANIMALS: 137 dogs with gastric dilatation-volvulus. PROCEDURE: Signalment; frequency of preoperative and postoperative treatments and complications; intraoperative findings; surgical technique; and hematologic, serum biochemical, and electrocardiographic results were recorded, evaluated for association with mortality, and compared between institutions. RESULTS: Mortality did not differ between institutions, and overall mortality was 18% (24/137). Surgical techniques differed between institutions, but were not associated with mortality. Gastric necrosis was associated with significantly higher mortality (46%; 13/28). When partial gastrectomy or splenectomy was performed, mortality (35 and 32% or 8/23 and 10/31, respectively) was significantly increased. Splenectomy was performed in 11 of 23 dogs requiring partial gastrectomy, and when both procedures were performed, mortality (55%; 6/11) was significantly increased. Preoperative cardiac arrhythmias were associated with significantly higher mortality (38%; 6/16). Mortality in dogs > 10 years old was not significantly greater than that in younger dogs. CLINICAL IMPLICATIONS: Patient management differences between practices did not seem to influence survival in dogs with surgically managed gastric dilatation-volvulus. Signalment, including age, did not influence mortality. Gastric necrosis, gastric resection, splenectomy, and preoperative cardiac arrhythmias were associated with mortality > 30%.

Evaluation of a hypertonic sodium chloride/dextran solution for treatment of traumatic shock in dogs.

OBJECTIVE: To compare the efficacy of 7% NaCl solution (hypertonic saline) in 6% dextran 70 solution (HSD) with that of lactated Ringer's solution (LRS) for treatment of dogs in traumatic shock. DESIGN: Prospective, randomized, clinical study. ANIMALS: 16 traumatized adult dogs with clinical signs of shock. PROCEDURE: Physical, hemodynamic, blood gas, and clinical chemistry measurements were performed prior to treatment. Initial treatment consisted of HSD (n = 8) or LRS (n = 8) administered as a bolus (5 ml/kg of body weight, IV) over a 3-minute period, followed by administration of additional LRS and other treatments to restore hemodynamic and physical criteria to within reference limits. Measurements were repeated for 3 hours after initial treatment. The volumes of LRS and HSD administered were recorded hourly. Degree of injury was scored by using a trauma severity index. RESULTS: Dogs responded similarly to the treatments, and all but 3 dogs survived to be discharged. The amount of fluid administered to dogs in the HSD group over the final 2 hours of the study was significantly less than that administered to the dogs in the LRS group. Serum sodium concentration and osmolality of the dogs in the HSD group were not significantly greater than those values in the LRS group. Bradyarrhythmias were observed in 2 dogs in the HSD group. CLINICAL IMPLICATIONS: Hypertonic sodium chloride/dextran solution is safe and effective for resuscitating dogs in traumatic shock. Seven percent NaCl in 6% dextran 70 may reduce the need for isotonic fluids in the hours after initial resuscitation.

A design study for an accelerator-based epithermal neutron beam for BNCT.

An achievable design concept for a boron neutron capture therapy (BNCT) facility, based on a high-current, low-energy proton accelerator, is described. Neutrons are produced within a thick natural lithium target, under bombardment from protons with an initial energy between 2.5 and 3.0 MeV. The proton current will be up to 10 mA. After gamma-ray filtering, the neutrons are partially moderated to epithermal energies within a heavy-water moderator, poisoned with 6Li to remove thermal neutrons. Monte Carlo modelling has been used to predict system performance in terms of neutron fluence rate and neutron and gamma-ray dose at the patient position. The relationship between the system performance and key parameters, such as proton energy, moderator depth and 6Li concentration, has been investigated. With a proton current of 10 mA, the facility is capable of providing a therapy beam with a useful neutron fluence rate of 10(9) cm-2 s-1 and a neutron dose per unit fluence of less than 6 x 10(-13) Gy cm2, with a gamma-ray contamination of the therapy beam of about 10(-13) Gy cm2.