Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Concentrations of interleukin-6, -8, -10 and tumour necrosis factor-α in the faeces of dogs with acute diarrhoea.

AIM: To compare the concentration of faecal cytokines interleukin (IL)-6, -8, -10, and tumour necrosis factor (TNF)-α in dogs with acute diarrhoea with clinically normal (non-diarrhoeic) dogs. METHODS: A total of 14 dogs presenting with acute diarrhoea, and 25 dogs with no history of gastrointestinal signs in the 2 months prior to enrolment, were recruited from two veterinary hospitals in Melbourne, Australia. Concentrations of IL-6, -8, -10, and TNF-α were measured in faecal samples using canine-specific ELISA. RESULTS: The diarrhoeic dogs were diagnosed with or managed for acute gastroenteritis (n = 6), extra-intestinal neoplasia (n = 2), parvoviral enteritis (n = 1), hepatopathy (n = 1), acute pancreatitis (n = 1), hypoadrenocorticism (n = 1), gastric dilatation volvulus (n = 1) and myelopathy (n = 1). IL-6 was detectable in the faeces of 10/14 (71%) diarrhoeic and 7/25 (28%) non-diarrhoeic dogs, and median concentrations were 10.8 (min 0.0, max 54.0) and 2.0 (min 0.0, max15.0) pg/mL, respectively (p = 0.01). IL-8 was detectable in the faeces of all diarrhoeic and 11 non-diarrhoeic dogs, and median concentrations were 149.7 (min 3.72, max 730.1) and 3.4 (min 0.0, max 22.5) pg/mL, respectively (p < 0.001). TNF-α was detected in the faeces of two of the diarrhoeic dogs (3.4 and 15.6 pg/mL) and none of the non-diarrhoeic dogs. IL-10 was not detected in the faeces of any dog. CONCLUSIONS: Faecal concentrations of IL-6 and -8 were higher in diarrhoeic compared to non-diarrhoeic dogs, and are therefore potential candidates for non-invasive biomarkers to assess the severity and resolution of acute intestinal disease in dogs. However their correlation with disease progression and severity needs to be further investigated before their full clinical application can be determined.

Gastrokine mRNA expression in gastric tissue from dogs with helicobacter colonisation but without inflammatory change during treatment.

Gastrokines (GKNs) are bioactive substances secreted by gastric cells. Evidence supports functional roles for GKNs in gastric homeostasis, immune responses and tumour suppression. Down-regulation has been reported in Helicobacter pylori associated gastritis and other inflammatory gastrointestinal conditions in mice and people. The aim of this study was to evaluate GKN gene expression in dogs positive for other Helicobacter spp. both before and after treatment. Expression of Gkn-1 and Gkn-2 mRNA was studied in endoscopic biopsy samples collected from seven healthy dogs over three time-points pre- (T0) and at 1 and 18 weeks post-treatment for Helicobacter spp. colonisation (T1 & T2). The relative expression software tool (REST) was used to provide efficiency corrected expression ratios for comparisons between groups and these results were compared to a standard 2ΔΔCT methodology. Compared with T1 Gkn1 and Gkn2 mRNA expression was greater at T0 by a mean factor of 2.53 (SE=1.83-3.54) for Gkn1 (P=0.000) and 2.85 (SE=2.23-3.75) for Gkn2 (P=0.000). This difference was attenuated when comparisons were made between T0 and T2. Histopathological evidence of gastritis was not present in any Helicobacter spp. positive sample. When compared to post-eradication samples Gkn gene expression is increased in the presence of Helicobacter spp. in dogs without evidence for concurrent inflammation. Further evaluation is required to determine the relevance of this finding, however given a suspected role in gastric homeostasis, up-regulation of GKN1 and GKN2 could limit development of gastritis in Helicobacter spp. positive dogs.

Comparison of in vivo confocal endomicroscopy with other diagnostic modalities to detect intracellular helicobacters.

Intracellular colonisation may serve as a protected niche where Helicobacter spp. organisms evade effective treatment. In dogs, non-Helicobacter pylori-helicobacters are frequently intracellular. Confocal endomicroscopy allows in vivo gastrointestinal imaging and has aided real-time identification of Helicobacter pylori and other intracellular and mucosally associated bacteria. The objectives of this study were: (1) to determine the utility of confocal endomicroscopy to identify non-Helicobacter pylori-helicobacters compared with other diagnostic modalities, and (2) to assess its ability to identify intracellular organisms. Fourteen clinically healthy dogs underwent standard gastroduodenoscopy followed by confocal endomicroscopy using topical acriflavine. Confocal images were obtained from at least five gastric sites. Endoscopic biopsies were obtained for histopathology, PCR and fluorescence in situ hybridisation (FISH). Methodologies were compared for their ability to determine the presence and spatial distribution of gastric helicobacters in dogs. Confocal endomicroscopy provided high quality images allowing in vivo identification of non-Helicobacter pylori-helicobacters in 13 dogs. Histopathology identified helicobacters in 11 dogs. Organisms were identified within the superficial gastric mucus and within gastric pits, and distribution throughout the stomach was diffuse and multi-focal. Confocal endomicroscopy findings correlated with PCR and FISH post-procedure analysis. Only FISH identified intracellular organisms, which were present in 13/14 dogs. Confocal endomicroscopy provided in vivo histology images and was capable of identifying non-Helicobacter pylori-helicobacters during gastroscopy, but was unable to identify intracellular organisms using the current fluorophore protocol.

A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer.

BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial.

BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. RESULTS: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted.

In vivo histologically equivalent evaluation of gastric mucosal topologic morphology in dogs by using confocal endomicroscopy.

BACKGROUND: Confocal endomicroscopy (CEM) is an endoscopic technology permitting in vivo cellular and subcellular imaging. CEM aids real-time clinical assessment and diagnosis of various gastrointestinal diseases in people. CEM allows in vivo characterization of small intestinal mucosal morphology in dogs. OBJECTIVE: To determine the feasibility of CEM to evaluate gastric mucosal morphology in dogs and to characterize the appearance in healthy dogs. ANIMALS: Fourteen clinically healthy research colony dogs. METHODS: Experimental study. Under general anesthesia, dogs underwent standard endoscopic evaluation and CEM of the gastric mucosa. In the initial 6 dogs, fluorescent contrast was provided with the fluorophore acriflavine (0.05% solution), applied topically. Subsequently, 8 dogs were assessed using a combination of fluorescein (10% solution, 15 mg/kg IV), followed by acriflavine administered topically. For each fluorophore, a minimum of 5 sites were assessed. RESULTS: Confocal endomicroscopy provided high quality in vivo histologically equivalent images of the gastric mucosa, but reduced flexibility of the endoscope tip limited imaging of the cranial stomach in some dogs. Intravenous administration of fluorescein allowed assessment of cellular cytoplasmic and microvasculature features. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing additional evaluation of nuclear morphology. Identification of Helicobacter-like organisms was possible in 13 dogs. CONCLUSION AND CLINICAL IMPORTANCE: Confocal endomicroscopy provides in vivo images allowing assessment of gastric mucosal morphology during endoscopy, potentially permitting real-time diagnosis of gastrointestinal disease.

In vivo confocal endomicroscopy of small intestinal mucosal morphology in dogs.

BACKGROUND: Confocal endomicroscopy (CEM) is an endoscopic technology that permits in vivo cellular and subcellular imaging of the gastrointestinal mucosa. OBJECTIVE: To determine the feasibility of CEM to evaluate small intestinal mucosal topologic morphology in dogs and to characterize the appearance in healthy dogs. ANIMALS: Fourteen clinically healthy research colony dogs. METHODS: Experimental study. Dogs were anesthetized for standard endoscopic evaluation of the small intestine followed by CEM. Two fluorophores were used to provide contrast: fluorescein (10% solution, 15 mg/kg IV) before administration of topical acriflavine (0.05% solution) via an endoscopy spray catheter. A minimum of 5 sites within the small intestine were assessed and at each location, sequential adjustment of imaging depth allowed collection of a three-dimensional volume equivalent to an 'optical biopsy'. CEM-guided pinch biopsies were obtained for histologic examination. RESULTS: CEM provided high-quality in vivo cellular and subcellular images. Intravenous administration of fluorescein provided sufficient contrast to allow assessment of the vasculature, cellular cytoplasmic features and goblet cell numbers, and distribution. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing evaluation of nuclear morphology. Quality of captured images was occasionally affected by motion artifact, but improved with operator experience. CONCLUSION AND CLINICAL IMPORTANCE: CEM provides in vivo images that allow for cellular and subcellular assessment of intestinal mucosal morphology during endoscopy. This has implications for aiding in vivo diagnosis of gastrointestinal disease.

Immune-mediated myasthenia gravis in a methimazole-treated cat.

A 12-year-old female neutered ragdoll crossbred cat was presented for investigation of generalised weakness and regurgitation. The cat was being treated with transdermal methimazole for hyper-thyroidism, which had been diagnosed 10 weeks previously. An acetylcholine receptor antibody titre was consistent with acquired myasthenia gravis. Withdrawal of methimazole and treatment with pyridostigmine was followed by resolution of clinical signs and reduction of the acetylcholine -receptor antibody titre. Medical control of hyperthyroidism was subsequently achieved with carbimazole, administered in conjunction with pyridostigmine, and no recurrence of clinical signs was observed. Myasthenia gravis is an uncommon but clinically significant adverse effect of methimazole therapy in cats, and may be caused by immunomodulatory properties of this drug. An adverse drug reaction should be considered in cats receiving methimazole that develop myasthenia gravis, and potentially also other immune-mediated disorders.

Masitinib as a chemosensitizer of canine tumor cell lines: a proof of concept study.

Masitinib, a selective tyrosine kinase inhibitor, has previously been shown to enhance the antiproliferative effects of gemcitabine in human pancreatic cancer, demonstrating potential as a chemosensitizer. This exploratory study investigated the ability of masitinib to sensitize various canine cancer cell lines to doxorubicin, vinblastine, and gemcitabine. Masitinib strongly sensitized histiocytic sarcoma cells to vinblastine (>70-fold reduction in IC(50) at 5 µM masitinib), as well as osteosarcoma and mammary carcinoma cells to gemcitabine (>70-fold reduction at 5-10 µM). In addition, several cell lines were sensitized to doxorubicin (2-10-fold reduction at 10 µM). These data establish proof-of-concept that masitinib in combination with chemotherapeutic agents can generate synergistic growth inhibition in various canine cancers, possibly through chemosensitization. The findings justify further investigation into those combinations that may potentially yield therapeutic benefit.

Prospective determination of the specificity of a commercial snake venom detection kit in urine samples from dogs and cats.

OBJECTIVE: To determine the specificity of a snake venom detection kit in urine samples from dogs and cats presenting to a referral centre for diseases unrelated to snake envenomation. DESIGN: Urine was collected from 50 dog and 25 cats presented for investigation and treatment of diseases unrelated to snake envenomation. Urine was collected as a voided sample, by cystocentesis or by catheterisation, and routine urinanalysis was performed. Snake venom testing was performed within 2 h of collection using a commercially available snake venom detection kit, which was observed continuously during the 10-min colour reaction phase for evidence of a visible colour indicating a positive test. RESULTS: No false-positive reactions occurred in any sample analysed. CONCLUSION: The snake venom detection kit appears to have 100% specificity for using urine as a test sample.

Clinical remission of idiopathic hypereosinophilic syndrome in a Rottweiler.

Idiopathic hypereosinophilic syndrome (HES) is a rare syndrome for which Rottweilers appear to over-represent the canine cases. A 6-month-old female entire Rottweiler presented with seizures following a traumatic incident. The dog was identified as having a marked, sustained eosinophilia and investigations did not identify an underlying cause. Concurrently, the dog had chronic eosinophilic hepatitis with impaired liver function and mesenteric eosinophilic lymphadenitis. The dog went on to have spontaneous resolution of HES and normal liver function was subsequently documented. To date, the dog is still alive, more than 4 years after initial presentation. The diagnosis of idiopathic HES in Rottweilers may not carry a poor prognosis and the condition may spontaneously resolve, even in cases with documented organ damage.

Remission of histiocytic ulcerative colitis in Boxer dogs correlates with eradication of invasive intramucosal Escherichia coli.

BACKGROUND: Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology. HYPOTHESIS: Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission. ANIMALS: Seven Boxer dogs with HUC. METHODS: Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli. RESULTS: Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7 + or - 3.06 mg/kg q24 h, for 9.5 + or - 3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17-62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed. CONCLUSIONS AND CLINICAL RELEVANCE: The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli.

Phase 1 dose-escalation study of oral tyrosine kinase inhibitor masitinib in advanced and/or metastatic solid cancers.

BACKGROUND: Masitinib is a tyrosine kinase inhibitor with a pre-clinical profile suggesting greater affinity and selectivity in vitro for the wild-type c-Kit receptor and its juxtamembrane mutation than imatinib. METHODS: This dose-escalation study was conducted in patients with advanced and/or metastatic cancer to determine the maximum tolerated dose (MTD) for orally administered masitinib over a 12-week period. Secondary objectives were a clinical assessment of masitinib's activity in cancer patients and establishment of a pharmacokinetic profile. RESULTS: Forty patients with various solid tumours (predominantly GIST, 19 patients) were treated with masitinib at doses ranging between 0.7 and 17.2mg/kg/day. Although the MTD was not formally reached, an acceptable dose for chronic use was identified at 12 mg/kg/day. Treatment-related AEs were frequent (38/40 patients), however, the majority were grade 1 or 2 and demonstrated dose dependency at higher concentrations. Pharmacokinetic results showed a linear, dose-dependent increase of C(max) and AUC. One of two GIST patients with imatinib intolerance had a partial response at 11.1mg/kg/day. About 29% of the imatinib-resistant GIST population and 38% of the overall population had stable disease. CONCLUSIONS: The safety profile of masitinib at 12 mg/kg/day b.i.d. for the treatment of solid cancers appears favourable and compatible with a long-term regimen. Tumour control rate in imatinib-resistant patients was encouraging, hence, the activity of masitinib in c-Kit expressing tumours, such as GIST, warrants further exploration as first-line anticancer therapy as well as for imatinib-resistant patients.

Concurrent sialocoele and necrotising sialadenitis in a dog.

A seven-year-old male, entire rottweiler was presented to Murdoch University Veterinary Hospital with a 24 hour history of blindness, chemosis, exophthalmus, pain on opening the mouth and hypersialism. Bilateral mandibular and zygomatic salivary gland enlargement with concurrent bilateral zygomatic salivary gland sialocoeles were identified. The cause of the mandibular salivary gland enlargement was confirmed as necrotising sialadenitis, while the cause of the zygomatic gland enlargement was presumed to be because of a similar disease process. No underlying aetiology was identified. Treatment consisted of supportive management, corticosteroids and paracentesis of the sialocoeles and resulted in resolution of the salivary gland enlargement and the associated clinical signs. This is an unusual presentation of salivary gland disease in the dog with multiple gland involvement and a spectrum of disease processes occurring at the same time.

Lymphocytic-plasmacytic thyroiditis and glomerulonephritis in a boxer.

An 18-month-old boxer was presented for investigation of profound lethargy, and primary hypothyroidism was diagnosed. A strong antithyroglobulin antibody titre was also present, indicating lymphocytic (immune-mediated) thyroiditis as the cause of hypothyroidism. A concurrent protein-losing glomerulonephropathy was also detected, although the aetiology could not be determined at initial presentation. Thyroid replacement and dietary therapy were prescribed. The dog improved clinically for approximately 12 months when it was re-presented with poorly controlled hypothyroidism and renal failure. Postmortem examination confirmed the presence of lymphocytic-plasmacytic thyroiditis, in conjunction with membranoproliferative glomerulonephritis and renal failure.

Treatment of insulinoma in a springer spaniel with streptozotocin.

An eight-year-old, female springer spaniel was treated for metastatic insulinoma with a single intravenous dose of 500 mg/m2 streptozotocin (SZN), and pre- and post-treatment diuresis. A tapering dose of corticosteroids was also administered over a 28 day period. SZN and corticosteroid administration resulted in resolution of hypoglycaemia and subsequent development of diabetes mellitus. Further metastases caused cervical spinal pain and the dog was euthanased 118 days after SZN administration. SZN can be safely used for the treatment of canine insulinoma, but, when compared with other published cases, a marked variation in clinical response to this drug exists and further study is warranted.

A quantitative evaluation of spurious results in the infrared spectroscopic measurement of CO2 isotope ratios.

The possible generation of spurious results, arising from the application of infrared spectroscopic techniques to the measurement of carbon isotope ratios in breath, due to coincident absorption bands has been re-examined. An earlier investigation, which approached the problem qualitatively, fulfilled its aspirations in providing an unambiguous assurance that 13C16O2/12C16O2 ratios can be confidently measured for isotopic breath tests using instruments based on infrared absorption. Although this conclusion still stands, subsequent quantitative investigation has revealed an important exception that necessitates a strict adherence to sample collection protocol. The results show that concentrations and decay rates of the coincident breath trace compounds acetonitrile and carbon monoxide, found in the breath sample of a heavy smoker, can produce spurious results. Hence, findings from this investigation justify the concern that breath trace compounds present a risk to the accurate measurement of carbon isotope ratios in breath when using broadband, non-dispersive, ground state absorption infrared spectroscopy. It provides recommendations on the length of smoking abstention required to avoid generation of spurious results and also reaffirms, through quantitative argument, the validity of using infrared absorption spectroscopy to measure CO2 isotope ratios in breath.

Optimized intensity-modulated arc therapy for prostate cancer treatment.

We recently implemented intensity-modulated arc therapy (IMAT) at our institution. In this study, we evaluate the dosimetric merits of the application of this technique to the treatment of prostate cancer. Each IMAT treatment plan incorporated bilateral overlapping arcs. The dose from each beam segment was computed using the three-dimensional dose model of a clinical treatment planning system (Render Plan 3.5, Precision Therapy). The weights assigned to the individual arc segments were optimized using a gradient search method. For 12 patients, comparisons were made between the IMAT treatment plans and corresponding plans using fixed cone-beam intensity-modulated radiotherapy (IMRT) from a commercial inverse planning system (CORVUS, NOMOS Corp.). We found that the optimized IMAT treatments produced similar dose distributions to the IMRT deliveries. Compared with the IMRT treatments, the IMAT treatments produced slightly less target dose homogeneity with consistently greater sparing of the rectum in regions of lower dose. The trade-off between target dose conformity and rectum sparing can be adjusted in both optimization procedures. Because the total beam-on time for IMAT delivery is 1 to 2 minutes with approximately 5-6 minutes of patient setup time, the delivery efficiency of the IMAT treatment was significantly better than the multiple-beam IMRT treatment.

Review of feline pancreatitis part one: the normal feline pancreas, the pathophysiology, classification, prevalence and aetiologies of pancreatitis.

The cellular mechanisms involved once pancreatitis has been initiated are reasonably well understood. The events leading up to this process are less well established. Much of our current understanding of pancreatitis in cats has been determined from experiments in cats or extrapolated from other species. The normal anatomy and function of the pancreas and a review of the current state of knowledge about the pathophysiology of pancreatitis is discussed. The current prevalence of feline pancreatitis is unknown, but the disease is being reported with increasing frequency. The aetiology of pancreatitis and the types of pancreatic inflammation present in cats is different from other species, such as the dog, a species where the disease is considered more common. Concurrent diseases are often present that may be more serious than the pancreatic inflammation and the treatment of these diseases is often complicated by pancreatitis.