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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 immunopheno-type (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 sub-stage 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. (J Am Vet Med Assoc 2021;259:62–71)

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.

The FMR1 premutation, caused by a CGG trinucleotide repeat expansion on the FMR1 gene, has been identified as a genetic risk factor for mood and anxiety disorders. Building on recent studies identifying increased risk for mood and affective disorders in this population, we examined effects of potential protective factors (optimism, religion, hope) on depression and anxiety diagnoses in a prospective, longitudinal cohort.Eighty-three women with the FMR1 premutation participated in the Structured Clinical Interview for DSM-IV-TR Disorders at two-time points, 3 years apart. Participants also completed measures of optimism, religion, personal faith, hope, and child and family characteristics. We used logistic regression to examine correlates of major depressive disorder (MDD) and anxiety disorders at the initial assessment, as well as predictors of the diagnostic course over time.Lower optimism and higher religious participation relevant to fragile X syndrome at the initial assessment were associated with a lifetime history of MDD. Lower optimism also predicted the occurrence and reoccurrence of an anxiety disorder 3 years later.In women with the FMR1 premutation, elevated optimism may reduce the occurrence or severity of MDD and anxiety disorders. These findings underscore the importance of supporting mental health across the FMR1 spectrum of involvement.

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/m2 body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m2 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/m2 of CCNU combined with 250 mg/m2 of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.

The goal of the current study was to determine the efficacy of oral docetaxel in combination with cyclosporine in the treatment of canine epithelial cancer. Requirements for eligibility were histological confirmation of epithelial neoplasia, measurable disease, no chemotherapy treatment within 2 weeks, and a life expectancy of ≥ 3 months. Fifty-one dogs were enrolled. All dogs received 1.625 mg kg(-1) of docetaxel with 5 mg kg(-1) of cyclosporine (DT/CSA) by gavage. Ten dogs had progressive disease at 2 weeks, one dog died, and one dog was withdrawn from the study. Thirty-nine dogs were given a second dose of DT/CSA, three each receiving a third or fourth dose. Eight dogs had a dose reduction (1.5 mg kg(-1)) and six dogs had treatment delays primarily for gastrointestinal toxicity. The overall response rate was 16.7% (8/48 had a partial response there were no complete responses). The highest response rate was seen in dogs with oral squamous cell carcinoma (50%; 6/12).

The goal of this study was to survey veterinarians regarding their current initial diagnostic and treatment recommendations for dogs with substage-a high-grade multicentric lymphoma. A written survey was conducted at the 2009 Veterinary Cancer Society conference asking veterinarians to provide demographic information, initial staging diagnostics and treatment recommendations for canine lymphoma. The most commonly recommended staging diagnostics were complete blood count (100%), chemistry panel (100%), urinalysis (85%), lymph node cytology (88%), thoracic radiographs (84%), immunophenotyping (76%) and abdominal ultrasound (75%). The most commonly used first-line B-cell protocols combined the drugs L-asparaginase, cyclophosphamide, doxorubicin, vincristine and prednisone (L-CHOP, 51%). CHOP (30%) and other CHOP-based protocols (12%) were used as well. Thirty-one percent of responders treated B- and T-cell lymphomas differently. Protocol lengths varied from ≤ 16 weeks to >2 years. Current staging and treatment recommendations for canine lymphoma are varied. Efforts to standardize recommendations should be considered.

Questionnaires completed by pet owners are widely used instruments to monitor adverse gastrointestinal (GI) effects in the owners' animals undergoing chemotherapy and for reporting toxicoses in clinical trials; however, no questionnaires have been formally evaluated. This study compares two questionnaire-based evaluations of adverse GI events: a basic, open-ended questionnaire and a detailed questionnaire modelled after the grading in the Veterinary Co-operative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE). Owners completed both questionnaires after their dog or cat received moderately emetogenic chemotherapy. Results were used to derive toxicity grades for anorexia, vomiting and diarrhoea. We evaluated 123 pairs of questionnaires. Disagreement in grade of anorexia, vomiting and diarrhoea was found in 24, 7 and 13% of paired questionnaires, respectively (κ = 0.63, 0.83 and 0.71, respectively). Although 'good' to 'very good' agreement was found, the potential for only 'fair' agreement between questionnaire methods is of concern and suggests a need to adopt a standardized form.

An L-CHOP protocol with interposed treatments of CCNU and MOPP (L-CHOP-CCNU-MOPP) was evaluated in 66 dogs with stages III-V lymphoma. Results were compared with a historical group of 71 dogs treated with an L-CHOP protocol. Complete remission (CR) rates (85 and 80%, respectively) did not differ significantly between protocols (P = 0.48). First CR duration for dogs treated with L-CHOP-CCNU-MOPP was significantly longer: median, 317 days; 2-year CR rate, 35% versus median, 298 days; 2-year CR rate, 13%, P = 0.05). For the L-CHOP-CCNU-MOPP protocol, dogs in substage-b had a 4.3 times greater hazard of having a relapse than dogs in substage-a (P = 0.002). Frequency of adverse chemotherapy-associated gastrointestinal effects did not differ between protocols (P = 0.77). Neutropenia (primarily after CCNU) occurred more frequently in dogs treated with L-CHOP-CCNU-MOPP (P < 0.001). In summary, the L-CHOP-CCNU-MOPP protocol showed an improved duration of first CR as compared with an L-CHOP protocol, but the relevance of this finding might be subject to clinical judgement.

Background: Histiocytic sarcoma (HS) is an aggressive neoplasm in dogs, and in most instances, the disease is localized, but not amenable to surgical removal, or is disseminated. Affected patients usually die within 6 months. There have been no prospective studies to determine efficacy of single-agent chemotherapy in dogs with HS. Hypothesis: Single-agent CCNU [1-(2-chloroethyl)3-cyclohexyl-1-nitrosourea; lomustine] has antitumor activity against HS in dogs. Animals: Twenty-one dogs with histologically confirmed, nonresectable localized or disseminated HS. Methods: Prospective, open-label phase II clinical trial in which dogs with previously untreated HS were uniformly treated with CCNU as a single oral dosage of 90 mg/m2 every 4 weeks. The primary outcome measure was reduction in tumor size. Results: Fourteen dogs with disseminated HS and 7 with localized HS were enrolled between 1999 and 2008. Overall response rate was 29% (95% confidence interval [CI], 14–50%) for a median of 96 days (95% CI, 55–137 days). Three dogs (1 disseminated, 2 localized) had complete responses lasting for 54–269 days and 3 dogs (2 disseminated, 1 localized) had partial responses lasting for 78–112 days. Conclusions and Clinical Importance: CCNU, when used as a single agent, has activity against HS in dogs. Evaluation of CCNU postoperatively for dogs with resectable localized HS and as part of combination therapy for tumors that are nonresectable or disseminated should be considered.

Safety and efficacy of a protocol of alternating 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 70 mg m(-2)) and vinblastine (3.5 mg m(-2)), and prednisone (1-2 mg kg(-1); CVP) in dogs with mast cell tumours (MCT) were evaluated. A total of 17 dogs had nonresectable MCTs and 35 received CVP as adjunctive treatment to locoregional control of metastatic MCTs or grade III MCTs. Neutropenia with fever occurred in 8% of dogs after treatment with vinblastine and in 2% after treatment with CCNU. Persistent elevation of serum alanine transaminase, suggestive of hepatotoxicity, occurred in 9% of the dogs. Response rate in dogs with nonresectable MCTs was 65%; five achieved a complete response (median, 141 days) and six achieved a partial response (median, 66 days). Overall median progression-free survival (PFS) time in dogs treated in the adjuvant setting was 489 days. Dogs with grade III MCTs had shorter PFS compared with dogs with metastatic grade II MCTs (190 days versus 954 days; P < 0.001). Phase III studies are needed to provide reliable information about the comparative efficacy of this protocol.

This prospective study evaluated the efficacy and safety of hydroxyurea (HU) in dogs with measurable mast cell tumours (MCTs). Dogs were treated with HU at 60 mg kg(-1)per os q24h for 14 days then 30 mg kg(-1) q24h thereafter or until MCT recurrence. Forty-six dogs were enrolled. The overall response rate was 28%. Two dogs had a complete response (CR) for 256 and 448 days, respectively. Eleven dogs had a partial response for a median duration of 46 days (range, 28-189 days). Grade 2 to 4 neutropenia occurred in eight dogs and grade 4 thrombocytopenia in two. Grade 3-4 anaemia occurred in seven dogs; overall, there was a significant decrease in haematocrit after treatment with HU. The median drop in haematocrit was 10%. This study demonstrated that HU has activity in the treatment of MCTs with mild anaemia being the primary adverse event.

In mice and people, administering corticosteroids before chemotherapy can reduce the severity of myelosuppression without reducing antitumour effects. This study investigated whether pretreatment with dexamethasone would reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. Twenty-five dogs received dexamethasone [0.1 mg kg(-1) per os (PO) every 12 h] for 5 days and on the sixth day received CCNU (90 mg m(-2) PO). Historical dogs (n = 67) received CCNU alone (90 mg m(-2) PO). Forty-five percent of historical dogs had grade 4 neutropenia, while 64% of dogs pretreated with dexamethasone had grade 4 neutropenia (P = 0.16). Dexamethasone plasma levels were quantified by enzyme-linked immunosorbent assay in three healthy dogs. Peak plasma concentrations after a single oral 0.1-mg kg(-1) dose were

Background: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established. Hypothesis: Single-agent VBL has antitumor activity against MCTs in dogs. Animals: Fifty-one dogs with nonresectable grade II or III cutaneous MCTs. Methods: Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m2 (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m2 (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size. Results: Twenty-five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48–229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28–78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had

Background: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. Hypothesis: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. Animals: Twenty-three dogs with lymphoma or cutaneous mast cell tumors. Methods: Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2–3 weeks. Results: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. Conclusions and Clinical Importance: In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.

Individuals with fragile X syndrome (FXS), especially men, have long been described as presenting with significant behavioural challenges. Despite this known aspect of the phenotype, there has been little research exploring the prevalence, frequency, nature or consequences of aggressive behaviour in FXS.This study used survey methodology to gather caregiver reports on the types, frequency and severity of aggressive behaviour in 774 individuals with FXS.Based on caregiver report, nearly all (90%) male and female individuals were reported to have engaged in some aggression over the previous 12 months, with a third of male cases and slightly fewer than 20% of female cases being described as engaging in moderate to severe aggression or being diagnosed or treated for aggression. Further, aggressive behaviours in male individuals were serious enough that 30% had caused injuries to caregivers and 22% had caused injuries to peers or friends. Sensory issues and hyperactivity were significant predictors of the frequency of aggressive acts, while sensory issues and anxiety were predictive of the severity of aggression. Traditional behaviour management techniques as well as medication was described as the most common and successful treatment options.Aggressive behaviours are a significant concern for a subsample of both male and female individuals with FXS. Given that sensory concerns were predictive of both the frequency and the severity of aggression suggests these behaviours may be a reactive means of escaping uncomfortable situations.

Objective—To characterize the pharmacokinetic disposition of carboplatin and determine whether glomerular filtration rate (GFR) could be used to predict carboplatin clearance and myelotoxic effects in cats with tumors. Animals—10 cats with tumors. Procedure—Glomerular filtration rate was assessed in each cat by monitoring plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Each cat received carboplatin (200 mg/m2 of body surface area) administered as an IV bolus. Plasma platinum concentrations were measured via atomic absorption spectrophotometry, and pharmacokinetic analysis was performed. A CBC was performed weekly for each cat, and the correlation between the area under the concentration-versus-time curve (AUC) and the severity of myelosuppression was calculated. Least squares regression analysis was performed to determine whether GFR could be used to predict plasma platinum clearance (ClPt). Results—For all cats, AUC measurements ranged from 0.99 to 4.30 min·mg·mL–1. Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/µL. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The ClPt was predicted by use of GFR measurements (ClPt = 2.60 × GFR). A carboplatin dose prescription model was derived involving AUC, estimated ClPt, and body weight in kilograms (BWkg), in which dose = AUC × 2.60(GFR) × BWkg. Conclusions and Clinical Relevance—In cats, an individualized prescription strategy for carboplatin administration based on a targeted AUC and determination of GFR might more uniformly predict myelosuppression than that predicted by conventional dosing based on body surface area. (Am J Vet Res 2004;65:1502–1507)

Superconducting states with broken time reversal symmetry can cause arbitrary intrinsic phase shifts in Josephson junctions. It is shown that locally time reversal symmetry breaking states can occur at interfaces between d-wave superconductors for certain crystal alignments. This property could be detected in form of fractional magnetic flux quanta on Josephson junctions and modified phase slip effects.

Fragile X syndrome (FXS) is known to be associated with a range of developmental challenges, yet the occurrence and intensity of therapy services along with associated factors have not been determined.In a US national survey, caregivers provided information regarding the therapy services received by their sons (n = 1013) and daughters (n = 283) with FXS (from birth to 63 years; mean = 15.6 years, SD = 10.6). Caregivers reported (1) type, (2) amount, (3) location, and (4) overall satisfaction with services. Associations with other child variables and family income were also examined.Key findings included that 72% of males and 47% of females were currently receiving at least one type of therapy service; the most common services for both males and females were speech-language therapy (ST) and occupational therapy (OT). Overall, males were more likely to receive therapy services as well as a greater number of services than females. Autism status was significantly associated with both males and females receiving ST and males receiving OT and behaviour management therapy. Therapies were provided in a variety of locations, and parents were generally satisfied with the amount and quality of therapy services. Age-related declines were evident in the use of services for both males and females, with very few individuals receiving any therapy services after 20 years of age.This study provides a baseline description of the current state of therapy services for children with FXS, laying a foundation for future research and recommendations for service provision and policy.

Histiocytic sarcoma (HS) is an aggressive neoplasm in dogs, and in most instances, the disease is localized, but not amenable to surgical removal, or is disseminated. Affected patients usually die within 6 months. There have been no prospective studies to determine efficacy of single-agent chemotherapy in dogs with HS.Single-agent CCNU [1-(2-chloroethyl)3-cyclohexyl-1-nitrosourea; lomustine] has antitumor activity against HS in dogs.Twenty-one dogs with histologically confirmed, nonresectable localized or disseminated HS.Prospective, open-label phase II clinical trial in which dogs with previously untreated HS were uniformly treated with CCNU as a single oral dosage of 90 mg/m2 every 4 weeks. The primary outcome measure was reduction in tumor size.Fourteen dogs with disseminated HS and 7 with localized HS were enrolled between 1999 and 2008. Overall response rate was 29% (95% confidence interval [CI], 14–50%) for a median of 96 days (95% CI, 55–137 days). Three dogs (1 disseminated, 2 localized) had complete responses lasting for 54–269 days and 3 dogs (2 disseminated, 1 localized) had partial responses lasting for 78–112 days.CCNU, when used as a single agent, has activity against HS in dogs. Evaluation of CCNU postoperatively for dogs with resectable localized HS and as part of combination therapy for tumors that are nonresectable or disseminated should be considered.

Second-opinion histopathology is intended to detect clinically significant discrepancies that have a direct impact on patient care. We sought to determine if this practice at our institution affected patient management and prognosis. First- and second-opinion histopathology reports from cases were retrospectively reviewed. Reports were considered to be in diagnostic agreement, partial diagnostic disagreement or complete diagnostic disagreement. Four hundred and thirty cases were studied. In 70% of cases there was a diagnostic agreement. In 20% of cases, there was partial diagnostic disagreement, where diagnoses were the same but information such as grade or lymphatic and/or vascular invasion was changed. In 10% of cases, complete diagnostic disagreement resulted from a change in degree of malignancy (malignant to benign, or converse; 7%) or a change in cell type (3%). In 17% of the cases evaluated, the histopathology review prompted a change in treatment or prognosis. These findings support the use of second-opinion histopathology as an important part of patient care.

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.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.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%).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.

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 (99mTc-DTPA) to yield GFR99mTc-DTPA and serum clearance of iohexol to yield GFRIohexol. 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 (AUCTarget) and estimation of platinum clearance (CLPT) derived from GFR99mTc-DTPA as follows: dose = AUCTarget × 2.6 × GFR99mTc-DTPA × body weight, where AUCTarget is 2.75 min·mg·mL−1. Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR99mTc-DTPA and GFRIohexol were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CLPT could be predicted from GFR99mTc-DTPA or GFRIohexol (or both). Results—GFR99mTc-DTPA and GFRIohexol were strongly correlated (r = 0.90), but GFRIohexol values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR99mTc-DTPA (CLPT = 2.5 × GFR99mTc-DTPA) and to GFRIohexol (CLPT = [1.3 × GFRIohexol] + 1.4). Conclusions and Clinical Relevance—In cats, serum iohexol clearance was an accurate predictor of CLPT and can be used to calculate the carboplatin dose as follows: dose = AUCTarget × ([1.3 × GFRIohexol] + 1.4) × body weight.

Background: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy. Hypothesis: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma. Animals: Eighteen dogs with histologically confirmed GI lymphoma. Methods: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases. Results: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22–420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6–700 days). Dogs that failed to achieve a remission (10 versus 117 days; P= .002) or had diarrhea at initial presentation (70 versus 700 days; P < .001) had shorter survival times. Conclusion and Clinical Importance: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.

Background: Pleotropic-glycoprotein (P-gp)–mediated resistance is the usual cause of relapse in dogs with lymphoma. 1-(2-chloroethyl)3-cyclohexyl-1-nitrosurea (CCNU) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) are alkylating agents that are not affected by P-gp and lack cross-resistance to each other. A combination protocol offers the advantage of improved summation dose and synergistic activity. Hypothesis: A combination of CCNU and DTIC that is well tolerated can be used to treat dogs with lymphoma that developed resistance or failed to respond to previously administered chemotherapy. Animals: Fifty-seven dogs with lymphoma that were resistant to treatment with standard chemotherapy (l-CHOP; l-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone). Methods: Prospective phase I and II trials were performed. CCNU was given PO immediately before a 5-h IV infusion of DTIC. Concurrent antiemetics and prophylactic antibiotics were used. Treatments were administered every 4 weeks. Results: Based on the results of 8 dogs in the phase I study, CCNU at 40 mg/m2 PO combined with DTIC at 600 mg/m2 IV was used to treat 57 dogs with resistant lymphoma. Thirteen (23%) dogs had a complete response (CR) for a median of 83 days and 7 (12%) had a partial response for a median of 25 days. The median l-CHOP CR duration of the dogs that did not respond to CCNU-DTIC was significantly longer than that of the dogs that did achieve remission with CCNU-DTIC (225 days versus 92 days, P= .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/μL. Increases in alanine transaminase activity, possibly associated with hepatotoxicity, were detected in 7 dogs. Conclusions and Clinical Importance: A combination of CCNU and DTIC can be an effective option to rescue dogs with resistant lymphoma.

Objective—To determine the maximum tolerated dose and characterize the pharmacokinetic disposition of an orally administered combination of docetaxel and cyclosporin A (CSA) in dogs with tumors. Animals—16 client-owned dogs with metastatic or advanced-stage refractory tumors. Procedures—An open-label, dose-escalation, singledose, phase I study of docetaxel administered in combination with a fixed dose of CSA was conducted. Docetaxel (at doses of 1.5, 1.625, or 1.75 mg/kg) and CSA (5 mg/kg) were administered concurrently via gavage twice during a 3-week period. Plasma docetaxel concentrations were quantified by use of high-performance liquid chromatography, and pharmacokinetic disposition was characterized by use of noncompartmental analysis. Dogs' clinical signs and results of hematologic and biochemical analyses were monitored for evidence of toxicosis. Results—No acute hypersensitivity reactions were observed after oral administration of docetaxel. Disposition of docetaxel was dose independent over the range evaluated, and pharmacokinetic variables were similar to those reported in previous studies involving healthy dogs, with the exception that values for clearance were significantly higher in the dogs reported here. The maximum tolerated dose of docetaxel was 1.625 mg/kg. Gastrointestinal signs of toxicosis were dose limiting. Conclusions and Clinical Relevance—The absence of myelosuppression suggested that the docetaxelCSA combination may be administered more frequently than the schedule used. Further studies are warranted to evaluate combination treatment administered on a biweekly schedule in dogs with epithelial tumors.

In the context of a longitudinal study, we assessed the relationship between ratings of autistic behavior, FMR1 protein expression (FMRP), and the developmental trajectories of 55 young males with fragile X syndrome. Autistic behavior, as measured by the Childhood Autism Rating Scale, was not related to FMRP expression. However, autistic behavior was a significant predictor of both developmental status and developmental change. Boys with both autistic behavior and fragile X syndrome functioned at significantly lower levels of development and grew at significantly slower rates than those without autistic behavior. FMRP expression accounted for less variance in developmental level than did autistic behavior, and was not significantly related to slope (developmental change over time). No autistic behavior x FMRP interaction was found.

We interviewed 250 parents of Mexican and Puerto Rican origin living in the United States who had young children with developmental delays to determine the role of religion in their lives. Quantitative results indicate that parents largely viewed themselves as religious, were affiliated with a formal religion, and participated in religious activities. Most parents viewed both church and faith as supportive, but faith was shown to provide more support. Repeated measures a analysis of variance found some intragroup variations in religious support and changes in support after learning of the child's condition. Thematic analysis revealed specific religious beliefs and practices parents viewed as supportive, and content and cultural models analyses indicated the religious frameworks by which parents interpreted their child's disability.

To test the hypothesis that variability in development in fragile X syndrome is related to FMRP (the protein deficient in this syndrome expression), we studied 53 males between 23 and 98 months of age. For the entire group, which included males with either mosaism, partially methylated full mutation, and fully methylated full mutation, FMRP expression ranged from 1% to 40% and accounted for a small but significant amount of variance in level, but not rate, of total development as well as motor, social, adaptive, cognitive, and language development. For males with a fully methylated full mutation, the association was in the hypothesized direction, but not statistically significant. Findings support the hypothesized relationship between FMRP and individual capabilities but suggest that other factors also play a major role.

We compared the developmental status, functional abilities, and temperament of 31 young boys with fragile X syndrome (FXS) who did not have autism, matched on chronological age, gender, and race, with 31 boys with autism but no FXS. Children with autism exhibited a more variable profile of development in comparison with a relatively flat profile for children with FXS. Children with autism were significantly more delayed in social skills and were rated by observers as exhibiting a greater degree of impairment in cognitive, communication, and social skills. On temperament ratings, both groups were slower to adapt, less persistent, and more withdrawing than the reference group. Boys with FXS were rated as more active than the referent group, whereas boys with autism were rated as less intense, more distractible, having a higher threshold for response, and less rhythmic than the reference group. A smaller three-group analysis compared boys with FXS, boys with autism, and boys with both FXS and autism. Children with both autism and FXS were substantially more delayed than children with autism or FXS alone.

A sample of 57 boys with fragile X syndrome (fraX) between the ages of 24 and 133 months was rated using the Childhood Autism Rating Scale (CARS) to assess the extent to which autism and autistic features were evident in a young population. Fourteen subjects (approximately 25% of the sample) scored above the cutoff for autism, suggesting a relatively high incidence of autistic behavior. All but 2 of these 14 were in the mildly or moderately autistic range, however, and only a few items received severe ratings, suggesting that severe autism is relatively rare in fraX, at least during the early years. The CARS resulted in a continuum of autistic ratings in the fraX population, but no particular items on the CARS contributed disproportionately to autism ratings. A visual comparison of ratings on an autistic, non-fraX sample revealed similar profiles of ratings, suggesting that differentiating fraX and autism on the basis of CARS ratings is not likely. Within the fraX group, chronological age and socioeconomic status did not correlate with CARS ratings, but severity of delay was strongly related, such that more severely delayed children scored higher (more autistic) on the CARS.

Findings from a prospective longitudinal study of 46 boys with fragile X syndrome between the ages of 24 and 72 months were reported. Hierarchical linear modeling was used to construct and evaluate overall developmental trajectories and scores in five domains: Cognition, Communication, Adaptive, Motor, and Personal-Social. The children varied widely, with significant differences across individuals in both mean rate and level of performance. Overall development was significantly delayed, with a slope of .48--approximately half the rate expected for typically developing children. No differences were found in rates of growth across the five domains. Significant differences were found, however, in mean levels of performance. At every age tested, Motor and Adaptive scores were higher than Communication and Cognitive.

We argue that recent experiments by Kirtley et al. may show evidence of time reversal symmetry breaking in YBCO at crystal grain boundaries. We illustrate this through a Ginzburg-Landau model calculation. Further experimental tests are proposed., Comment: 10 pages, REVTeX 3.0

We consider a layered superconductor with a complex order parameter whose phase switches sign from one layer to the next. This system is shown to exhibit gapless superconductivity for sufficiently large interlayer pairing or interlayer hopping. In addition, this description is consistent with experiments finding signals of time-reversal symmetry breaking in high-temperature superconductors only at the surface and not in the sample bulk., Comment: 3 pages, REVTeX 3.0, no figures.

Communicative interactions of preschool children with and without disabilities in classrooms of same or mixed ages were compared. Sixteen children with developmental disabilities (most with mild or moderate mental retardation) and 32 children without disabilities between 1.5 and 4.5 years of age were randomly assigned at the beginning of the school year to either a same- or mixed-age grouping of 6 children. They were observed 6 months later interacting with classmates in a standard free-play environment. Results showed that children in mixed-age classes took more turns in conversations with partners with disabilities than did children in same-age classrooms. They also received more turns from their partners with disabilities, which were more often responses than initiations in the mixed-age as compared to same-age classes. In contrast, during communicative interactions with partners without disabilities, children in both types of classes did not significantly differ in number or types of turns. Children of a similar developmental level also had similar communicative interaction styles.

One aspect of family adaptation to a young child with disabilities was investigated through comparison of expressed needs of mothers and fathers and examination of the relation of those needs with selected child and family characteristics. A diverse sample of more than 400 parents completed the Family Needs Survey (BaileySimeonsson, 1988). A factor analysis of the items for mothers yielded six distinct factors. A confirmatory factor analysis of needs expressed by fathers indicated a structure that differed significantly from that found for mothers. Mothers expressed significantly more needs than did fathers. Although SES and disability type accounted for significant variance in needs of mothers, an examination of mean values suggested the effect to be of limited clinical significance.

The DMSO solution copolymerization of acrylonitrile and vinylidene chloride can be adequately described by the terminal-unit copolymerization model. The sequence distribution measured by 13C-NMR is in excellent agreement with the theoretically calculated diad, triad, and pentad distributions. The variation of glass transition temperatures with copolymer composition is explained by sequence distribution.

Spin-lattice relaxation times and nuclear Overhauser enhancements (NOE) for 13C nuclei in copolymers of acrylonitrile and vinylidene chloride were measured at 20.1 and 67.9 MHz. In the CCl2 region of the spectrum T1 and NOE values of the various resonances are equal within experimental error and are invariant to changes in composition. The T1 and NOE values of the CCl2 region, however, are not equal to those of the CH or CN region. As a result compositions cannot be calculated by direct comparison of the areas in the CCl2 region and either the CH or the CN region. Discrepancies can be corrected for the CH resonances by multiplication of the area by an empirical constant. A similar constant for the CN region is composition-dependent at 20.1 and 67.9 MHz. A chemical shift anisotropy mechanism is postulated as important for relaxation of the CN resonances. The overall influence of variable T1 and NOE values on quantitative determination of polymer composition is considered.

Results of a study of individual participation in interdisciplinary team meetings, with a focus on the participation behavior of professionals, paraprofessionals, and direct-care staff members, were reported. Several differences in observed and self-perceived participation were noted, with the general finding that professional staff members exhibited the highest levels of participation, whereas direct-care staff members exhibited the lowest levels of participation.

In this paper we describe a scale designed to measure individual participation in interdisciplinary team meetings. Data from an observational study of team meetings at a residential institution for severely and profoundly mentally retarded persons were used to examine the measurement characteristics of the scale. Acceptable levels of interobserver agreement were found. A principal components analysis demonstrated that participation is not a unitary construct, but consists of at least five relatively independent dimensions. A generalizability study indicated that participation varies across team meetings and suggested that at least two observations are needed to obtain an adequate picture of typical participation. A sample application of the scale was described, and implications of the scale for researchers and practitioners were discussed.