Retrospective evaluation of shock index and mortality in dogs with head trauma (2015-2020): 86 cases.

OBJECTIVE: To assess the relationship between shock index (SI) and mortality in dogs with head trauma (HT). A secondary objective was to compare SI with the animal trauma triage (ATT) score and Modified Glasgow Coma Scale (MCGS) score in HT cases. A tertiary aim was to assess if SI is predictive of survival to discharge or improvement in presenting neurologic signs. DESIGN: Retrospective study from January 2015 to December 2020. SETTING: Tertiary referral level II veterinary trauma center. ANIMALS: Eighty-six dogs with evidence of HT presenting through emergency for various traumas compared to 60 healthy control dogs. MEASUREMENTS AND MAIN RESULTS: SI was calculated using the quotient of heart rate over systolic blood pressure measured on presentation. SI was significantly higher in HT patients than healthy controls (P = 0.0019). SI was not significantly different between traumatic brain injury dogs that died or were euthanized and HT dogs that lived until the time of discharge (P = 0.98). SI was not significantly different between HT dogs that were neurologically normal at the time of discharge and HT dogs that were static or improved but not normal neurologically at the time of discharge (P = 0.84). In HT dogs, SI did not correlate with ATT score (P = 0.16) or MGCS score (P = 0.75). There was no significant difference in SI and length of hospitalization until death or discharge (P = 0.78). CONCLUSIONS: SI was significantly higher in HT patients compared to control patients. Interestingly, SI was not correlated with ATT score or MGCS score. The use of SI in HT patients warrants further investigation to assess the efficacy in predicting mortality.

Effect of Annona squamosa leaf extract on human promyelocytic leukemia cells subjected to oxidative stress.

OBJECTIVES: Annona squamosa has beneficial properties. However, its cytotoxicity and antioxidative effects on human promyelocytic leukemia cells (HL60) deserve investigation. Therefore, the efficacy of its crude extracts in offsetting damage in HL60 cells subjected to oxidative stress was studied. METHODS: Crude extracts at different concentrations were incubated with HL60 cells. The beneficial properties of the plant extract against oxidative damage were evaluated post-induction of oxidative stress utilizing hydrogen peroxide. RESULTS: Extracts at concentrations 600 and 800 µg/mL were most effective at increasing the viability of damaged cells compared to the control group after 48 h of incubation. Significant increases in lipid peroxidation were observed in exposed cells treated with 600 µg/mL extract after 72 h of incubation. Superoxide dismutase (SOD) and catalase activities significantly increased in exposed cells after 24 h of incubation at all extract concentrations. Exposed cells treated with 600 and 1,000 µg/dL of the extract showed significantly increased catalase activity after 48 h, and a similar profile was maintained after 72 h of exposure. SOD activity in exposed cells remained significantly increased at all treatment concentrations after 48 and 72 h of incubation. Treatment with 400, 600, and 800 µg/mL of the extract resulted in significantly increased reduced glutathione levels compared to the other groups after 24 and 72 h of incubation. However, after 48 h of incubation, significant increases were noted in glutathione levels in exposed cells incubated with either 400, 800, or 1,000 µg/mL extract. CONCLUSIONS: The findings suggest that A. squamosa might effectively protect against oxidative damage in a time and extract concentration-dependent manner.

Survival time for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone: the Canine Lymphoma Steroid Only trial.

OBJECTIVE: To evaluate survival times for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. ANIMALS: 109 client-owned dogs recruited from 15 institutions in the United States. PROCEDURES: Dogs were treated with prednisone at a dosage of 40 mg/m2, PO, once daily for 7 days and at a dosage of 20 mg/m2, PO, once daily thereafter. Quality of life (QOL) was assessed by owners with a visual analog scale when treatment was started (day 0), 1 and 2 weeks after treatment was started, and every 4 weeks thereafter. The primary outcome of interest was survival time as determined by the Kaplan-Meier method. Factors potentially associated with survival time were examined. RESULTS: Median overall survival time was 50 days (95% CI, 41 to 59 days). Factors associated with survival time included substage (a vs b) and immunophenotype (B cell vs T cell). Owner-assigned QOL scores on days 0 and 14 were significantly positively correlated with survival time. When QOL score was dichotomized, dogs with day 0 or day 14 QOL scores ≥ 50 had significantly longer survival times, compared with dogs with day 0 or day 14 QOL scores < 50. No variables were predictive of long-term (> 120 days) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that survival times were short for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. Owner-perceived QOL and clinician-assigned substage were both associated with survival time. Findings provide potentially important information for clinicians to discuss with owners of dogs with lymphoma at the time treatment decisions are made.

Shock index is associated with mortality in canine vehicular trauma patients.

OBJECTIVE: To calculate and compare shock index (SI) in healthy dogs and vehicular trauma dogs (VT), determine the prognostic value of SI in VT dogs, and to assess the correlation between SI and the animal trauma triage score, modified Glasgow Coma Scale score, and lactate in VT dogs. DESIGN: Retrospective study from April 2016 to February 2018. SETTING: Twenty-four-hour tertiary referral level II trauma center. ANIMALS: One hundred twenty-one dogs presented to the emergency service for VT and 60 healthy control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate and systolic blood pressure were measured on each patient and used to calculate SI. SI was significantly higher in VT dogs compared to healthy control dogs (median SI, 1.0 vs 0.75; P < 0.0001). SI was significantly higher in those that died versus those that survived to discharge (median, 1.27 vs 0.96; P = 0.017). SI positively correlated with animal trauma triage score (95% confidence interval, 0.039-0.49; P = 0.019; r = 0.26) but did not with plasma lactate level at presentation (P = 0.068; r = 0.22) or modified Glasgow Coma Scale (P = 0.85; r = -0.021, 95% confidence interval, -0.24 to 0.20). CONCLUSIONS: SI is easy to calculate during triage of a trauma patient. Given its significant relationship with mortality, higher SIs should prompt the clinician to pursue additional monitoring, diagnostics, and intervention.

A connectome and analysis of the adult Drosophila central brain.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain.

Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons ­ compared to some 86 billion in humans ­ the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map ­ or connectome ­ the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Analysis of platinum content in biodegradable carboplatin-impregnated beads and retrospective assessment of tolerability for intralesional use of the beads in dogs following excision of subcutaneous sarcomas: 29 cases (2011-2014).

OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas. DESIGN Evaluation study and retrospective case series. SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs. PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed. RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.

Current Opinions on Stress-Related Mucosal Disease Prevention in Canadian Pediatric Intensive Care Units.

OBJECTIVE: To describe current opinions about stress-related mucosal disease (SRMD) prevention in Canadian pediatric intensive care units (PICUs). METHODS: A 22-question survey covering several aspects of SRMD was sent to all identified PICU attendings in Canada. RESULTS: Sixty-eight percent of identified attendings completed the questionnaire. Thirty-eight percent were based in Quebec, 31% in Alberta, and 31% from other provinces. Most attendings (78%) had worked in a PICU for 6 years or more. When asked about risk factors for prescribing SRMD prevention drugs (more than 1 answer was accepted), the most popular answers were prior history of gastric ulceration/bleeding (33 respondents), coagulopathy (28 respondents), and major neurologic insult (18 respondents). Almost half of the attendings (48%) mentioned that they prescribe SRMD prophylaxis directly upon PICU admission to more than 25% of their patients. Forty-nine percent of respondents subjectively estimated that clinically significant upper gastrointestinal bleeding (UGIB; defined as UGIB associated with either hypotension, transfusion within 24 hours of the event, or death) occurred in less than 1% of their patients. Fifty-seven respondents (93%) used ranitidine as first-line therapy (average dose: 4.1 mg/kg/day, mainly intravenously). As second-line therapy, 32 attendings (52%) used pantoprazole and 13 (21%) used omeprazole. CONCLUSIONS: Despite the paucity of guidelines on SRMD prevention and the low reported incidence of clinically significant UGIB, SRMD prevention is frequently used in Canadian PICUs. Ranitidine is the first-line drug used by most attendings.

Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

BACKGROUND: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy. METHODS AND FINDINGS: This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib. CONCLUSIONS: The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.

This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg ± 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg ± 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.

Esophageal foreign bodies in dogs: 34 cases (2004-2009).

OBJECTIVE: To characterize the clinical and radiographic signs, endoscopic findings, treatment, and outcome for dogs that present with esophageal foreign bodies (EFBs), and to identify factors associated with the severity of secondary esophagitis and length of hospitalization (LOH). DESIGN: Retrospective case series. SETTING: Private referral veterinary center. ANIMALS: Client-owned dogs. INTERVENTIONS: None. MEASUREMENTS: Medical records for 34 client-owned dogs with EFBs that had esophageal radiographs and that had undergone esophagoscopy were evaluated retrospectively. Information regarding clinical history, radiographic signs, findings at esophagoscopy, and outcome were recorded. RESULTS: The most common EFBs were bone (29.7%) and rawhides (29.7%). The median duration of clinical signs prior to initial presentation was 2.75 hours. Radiographically, EFBs were identified definitively in 30 dogs and questionably in 1. The most common location was in the caudal esophagus (59.3%). Esophagitis was not identified in 6 dogs; and was assessed as mild in 14, moderate in 9, and severe in 4. In 1 dog the degree of esophagitis could not be determined due to the presence of contrast agent. Dogs with longer duration of clinical signs and longer anesthesia times were more likely to have moderate or severe esophagitis. Median LOH was 19 hours. Dogs with longer duration of clinical signs, EFBs located in the caudal esophagus, and moderate or severe esophagitis had longer hospital stays. No dogs experienced long-term complications. Complication rate was 82.5% with 8 patients having more than 1 complication. CONCLUSIONS: While long-term prognosis is excellent, early intervention helps reduce short-term esophagitis and LOH.

Determination of strong ion gap in healthy dogs.

OBJECTIVE: To determine and compare reference intervals of the strong ion gap (SIG) in a group of healthy dogs determined with 2 different equations. DESIGN: Prospective observational study. SETTING: Tertiary referral and teaching hospital. ANIMALS: Fifty-four healthy dogs. INTERVENTIONS: None. MEASUREMENTS: Serum biochemistry and blood gas analyses were performed for each dog. From these values, SIG was calculated using 2 different equations: SIG(1) = SID(a) {[Na (+)] + [K(+)] - [Cl(-)]+ [2 × Ca(2+)] + [2 × Mg(2+)] - [L-lactate]}- SID(e) {TCO(2) + A(-)} and SIG(2) = [albumin] × 4.9-anion gap. Reference intervals were established for each SIG equation using the mean ± 1.96 × standard deviation (SD). RESULTS: For SIG(1), the median was 7.13 mEq/L (range, 1.05-11.30 mEq/L) and the derived reference interval was 1.85-10.61 mEq/L. Median SIG(2) was -0.22 mEq/L (range, -5.34-6.61 mEq/L) and the mean SIG(2) was -0.09 mEq/L (95% confidence interval for the mean, -0.82-0.65 mEq/L). The derived reference interval was -5.36-5.18 mEq/L. The results of the SIG calculations were significantly different (P < 0.0001) between the 2 equations used. CONCLUSION: The 2 equations used to calculate SIG yielded significantly different results and cannot be used interchangeably. The authors believe SIG(2) to be a more accurate reflection of acid-base status in healthy dogs, and recommend that this calculation be used for future studies.

The history of sleep medicine.

Sleep medicine as it is known today actually started as research and scientific study, not as clinical medicine. When one considers that sleep medicine today is in its infancy, it is obvious that there is much more to learn. The history of sleep dates back to the 1880s. However, the most significant developments that moved sleep forward into the practice of medicine, and eventually dentistry, occurred from the 1950s on. This article explores the highlights of the history of sleep and sleep medicine.

Screening and comprehensive evaluation for sleep related breathing disorders.

The dentist is well positioned to screen for patients at risk for a sleep disorders, most often a sleep related breathing disorder, and when adequately trained, can treat those diagnosed with sleep apnea using an oral appliance. This treatment requires some degree of training to be able to recognize the symptoms related to the more common sleep disorders. The dentist must determine if the patient is at risk for a sleep disorder through the use of screening questionnaires, reviewing the health history, and additional questioning of the patient.

Use of portable monitoring for sleep-disordered breathing treated with an oral appliance.

The potential use of a portable monitor to assess the outcome of treatment with an oral appliance would ideally be performed by the dentist who is managing the patient's sleep-disordered breathing. Portable monitoring is one of the most cost-effective ways to assess the response to the oral appliance, to determine if further adjustment to the appliance is needed, and to retest to determine the current status following any adjustment. This article emphasizes the use of portable monitors primarily for follow-up care and assessment as opposed to diagnosis or, as it is sometimes referred to, screening.

Oral bioavailability of DN101, a concentrated formulation of calcitriol, in tumor-bearing dogs.

PURPOSE: High-dose calcitriol (1,25-dihydroxyvitamin D(3)) has antineoplastic activity against a range of tumors and potentiates chemotherapeutic agents. In an earlier canine study, the MTD of intravenous (i.v.) calcitriol was 3.75 µg/kg, but polysorbate-associated hypersensitivity reactions were common. Use of commercially available oral calcitriol is limited by the absence of a formulation of suitable strength to allow administration of a reasonable number of caplets. This study evaluated the bioavailability of DN101, a concentrated oral calcitriol formulation specifically developed for anticancer applications. METHODS: An open-label, single-dose, 2-way crossover study was conducted. Dogs randomly received a single 3.75 µg/kg dose of calcitriol either i.v. or oral (as DN101), followed by cisplatin (60 mg/m(2)). Three weeks later, the alternate form of calcitriol was given prior to another dose of cisplatin. Dogs received antihistamines and corticosteroids prior to both treatments. Food was withheld for 12 h before and after therapy. Serum calcitriol concentrations were measured by radioimmunoassay. RESULTS: Ten tumor-bearing dogs received both i.v. and oral calcitriol. Six dogs experienced hypersensitivity reactions during i.v. calcitriol. Sequence of calcitriol administration (day-1 vs. day-21) by either i.v. or oral routes had no effect on the major calcitriol pharmacokinetic parameters. Oral calcitriol resulted in significantly lower values for AUC (P = 0.05) and prolonged T (1/2) (P = 0.003) when compared to i.v. Calcitriol oral bioavailability was highly variable among dogs (mean ± SEM, 71 ± 12.6%). CONCLUSIONS: This study demonstrates that a high-dose formulation of calcitriol has a moderate bioavailability in dogs, but inter-individual variability in PK parameters is similar to that observed in people. With this bioavailability, serum concentrations of calcitriol that exhibit antitumor activity in a preclinical murine model were achieved in some dogs. Exploration of methods to minimize variation in calcitriol systemic exposure is warranted.

Evaluation of serum iohexol clearance for use in predicting carboplatin clearance in cats.

OBJECTIVE: To determine whether a glomerular filtration rate (GFR) assay based on serum iohexol clearance can be used to predict carboplatin clearance in cats. ANIMALS: 10 cats with tumors. PROCEDURES: GFR was measured concurrently by use of plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) to yield GFR(99mTc-DTPA) and serum clearance of iohexol to yield GFR(Iohexol). A single dose of carboplatin was administered IV as a bolus. Dose was calculated by use of a target value for the area under the plasma platinum concentration-versus-time curve (AUC(Target)) and estimation of platinum clearance (CL(PT)) derived from GFR(99mTc-DTPA) as follows: dose = AUC(Target) x 2.6 x GFR(99mTc-DTPA) x body weight, where AUC(Target) is 2.75 min.mg.mL(-1). Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR(99mTc-DTPA) and GFR(Iohexol) were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CL(PT) could be predicted from GFR(99mTc-DTPA) or GFR(Iohexol) (or both). RESULTS: GFR(99mTc-DTPA) and GFR(Iohexol) were strongly correlated (r = 0.90), but GFR(Iohexol) values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR(99mTc-DTPA) (CL(PT) = 2.5 x GFR(99mTc-DTPA)) and to GFR(Iohexol) (CL(PT) = [1.3 x GFR(Iohexol)] + 1.4). CONCLUSIONS AND CLINICAL RELEVANCE: In cats, serum iohexol clearance was an accurate predictor of CL(PT) and can be used to calculate the carboplatin dose as follows: dose = AUC(Target) x ([1.3 x GFR(Iohexol)] + 1.4) x body weight.

Phase I evaluation of carboplatin by use of a dosing strategy based on a targeted area under the platinum concentration-versus-time curve and individual glomerular filtration rate in cats with tumors.

OBJECTIVE: To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUC(Target)) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUC(Target). ANIMALS: 32 cats with tumors. PROCEDURES: In each cat, plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid was measured to assess GFR. Carboplatin was administered IV. The dose was calculated by use of an equation as follows: Dose = AUC(Target) x 2.6 x GFR x body weight. Initial AUC(Target) was 2.0 min.mg.mL(-1) and was increased in increments of 0.50 min.mg.mL(-1) in cohorts of 3 cats. To assess myelotoxic effects, CBCs were performed weekly for > or = 4 weeks. Following identification of the maximum tolerated AUC(Target), additional cats were treated at that AUC(Target) and plasma platinum concentrations were measured in 6 cats. RESULTS: The AUC(Target) values ranged from 2.0 to 3.0 min.mg.mL(-1). Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUC(Target) was 2.75 min.mg.mL(-1). Nineteen cats received this dose of carboplatin; 13 became neutropenic, but only 1 developed severe neutropenia (< 500 neutrophils/microL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUC(Target) and the measured value ranged from -0.23 to 0.31 min.mg.mL(-1) (median, 0.20 min.mg.mL(-1)). CONCLUSIONS AND CLINICAL RELEVANCE: In cats, carboplatin-associated myelotoxicoses were accurately and uniformly predicted by use of the proposed dosing strategy. The maximum tolerated AUC(Target) for a single dose of carboplatin was 2.75 min.mg.mL(-1).