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OBJECTIVE Collaboration between primary care veterinarians (pcVets) and veterinary oncologists is common for dogs diagnosed with cancer, but no data exist that explore dog owner utilization and perceptions of collaborative care. The objectives were to describe dog owner perceptions of the value of collaborative veterinary cancer care and identify drivers of a positive collaborative care experience between the pcVet and oncologic specialists. SAMPLE 890 US dog owners who had pets diagnosed with cancer in the past 3 years. PROCEDURES Online contextual survey. Data were analyzed using group comparisons and multiple regression analysis. Significance was set at P < .05. RESULTS 76% of clients sought specialty care following cancer diagnosis in their dog. Seventy percent of owners across all income brackets indicated that referral to a specialist was a very good value based on money spent and outcomes. Delayed referral resulted in lower client satisfaction scores for pcVets. Top predictors of client satisfaction with pcVets were as follows: responsiveness to questions, staying involved with their dog’s care, and willingness to work with other veterinarians and specialists. For specialists, top predictors were as follows: providing accurate cost estimates, cancer knowledge, and effectiveness of care. Client perceptions of pcVets were 6 times more likely to improve following referral to a specialist. All were significant predictors of owner advocacy (P < .0001). CLINICAL RELEVANCE Dog owners perceived early collaboration between pcVets and specialists favorably, fostering client satisfaction and positive perceptions of the value for service provided for dogs diagnosed with cancer.

OBJECTIVE To determine the feasibility of endoscopic application of fibrin glue for the treatment of experimentally induced postintubation tracheal laceration (PITL) in feline cadavers. The secondary objective was to determine the optimal technique for application of the fibrin glue. ANIMALS 20 feline cadavers (n = 10 fresh and 10 frozen). PROCEDURES An experimentally induced tracheal rupture was created via overinflation of an endotracheal tube cuff. After endoscopic identification of the tracheal tear, fibrin glue was instilled into the tracheal defect in either a bridging or filling fashion. Following the procedure, the airway of each cat was examined and leak tested. Length of tear, volume of glue applied, procedural time, and glue efficacy were recorded. RESULTS Experimentally induced tracheal lacerations were full thickness with a mean length of 3.27 ± 0.96 cm. A complete seal was attained in 6 of the 9 fresh cadavers when filling the defect with fibrin glue. In the remaining 3 fresh cadavers, air leakage was restricted to the dorsal mediastinum. Bridging the defect with fibrin glue did not attain a seal in fresh or frozen cadavers. The median volume of glue used to fill defects in fresh cadavers was 0.5 mL (range, 0.4 to 2 mL). Procedural time for the application of fibrin glue was 10.5 ± 4.1 minutes for bridging the defect and 7.8 ± 1.5 minutes for filling the defect. CLINICAL RELEVANCE Endoscopic application of fibrin glue may be a feasible method of treatment for PITL in cats.

OBJECTIVE To utilize the geometry of superficial anatomic landmarks to guide incisional location and orientation for peripheral lymphadenectomy, document deep anatomic landmarks for lymphocentrum identification, and develop novel surgical approaches to the superficial cervical, axillary, and superficial inguinal lymphocentrums in dogs. ANIMALS 12 canine cadavers. PROCEDURES 2 cadavers were used for a pilot investigation to determine optimal body positioning, select superficial anatomic landmarks for lymphocentrum identification, and evaluate novel surgical approaches to the 3 lymphocentrums. These lymphocentrums were then dissected in 10 additional cadavers using these novel surgical approaches. Measurements of the distances from lymphocentrum to landmark and between landmarks were obtained for each lymphocentrum. Deep anatomic landmarks were recorded for each dissection. The mean and SD were calculated for each measurement and used to develop geometric guidelines for estimating the location of each lymphocentrum for these surgical approaches. RESULTS Each peripheral lymphocentrum was found in the same location relative to the respective, predetermined, superficial, anatomic boundaries in all cadavers. Briefly, the superficial landmarks to each lymphocentrum were as follows: (1) superficial cervical: wing of atlas, acromion process of scapula, greater tubercle of humerus; (2) axillary: caudal border of transverse head of superficial pectoral muscle, caudal triceps muscle, ventral midline; and (3) superficial inguinal: origin of pectineus muscle, ipsilateral inguinal mammary gland, ventral midline. The proposed superficial and deep surgical landmarks were identified within every cadaver. The previously undescribed surgical approaches were effective for lymphocentrum identification. CLINICAL RELEVANCE Anatomic landmarks provided in this study may help reduce surgical time and tissue trauma during peripheral lymphadenectomy in dogs. This study was also the first to describe a surgical approach to the superficial inguinal lymphocentrum and ventral approaches to the superficial cervical and axillary lymphocentrums and provided previously unpublished anatomic landmarks for a lateral approach to the superficial cervical lymphocentrum.

To report intraoperative and immediate postoperative complications associated with removal of metastatic iliosacral lymph nodes in dogs with apocrine gland anal sac adenocarcinoma.There were 136 client-owned dogs in the study.Retrospective multi-institutional study. The database of collaborating institutions was searched for dogs with metastatic apocrine gland anal sac adenocarcinoma that underwent lymphadenectomy for removal of one or more iliosacral lymph nodes. Information of signalment, hematological abnormalities, abdominal computed tomography or ultrasound findings, number and size of enlarged lymph nodes, intraoperative and postoperative complications, treatment and outcome were collected.The overall complication rate associated with metastatic iliosacral lymphadenectomy was 26.1%. The only intraoperative complication recorded was hemorrhage and was reported in 24 (17.6%) surgeries, 11 (45.8%) of which received a blood transfusion. Postoperative complications were reported in 10.4% of surgeries, and included edema formation (Complications associated with iliosacral lymphadenectomy for metastatic apocrine gland anal sac adenocarcinoma are relatively common and mostly relate to hemorrhage. These complications are significantly associated with the size of the extirpated metastatic lymph nodes.This retrospective study provides information for the clinician regarding the potential surgical complications for extirpation of metastatic iliosacral lymph nodes. These complications, although not common, can be severe and should be discussed with owners before surgery.Rapporter les complications peropératoires et postopératoires immédiates associées à l’ablation des ganglions lymphatiques ilio-sacrés métastatiques chez les chiens atteints d’un adénocarcinome des glandes apocrines des sacs anaux.Il y avait 136 chiens appartenant à des clients dans l’étude.Étude multi-institutionnelle rétrospective. La base de données des institutions collaboratrices a été recherchée pour les chiens atteints d’un adénocarcinome métastatique des glandes apocrines des sacs anaux qui ont subi une lymphadénectomie pour l’ablation d’un ou plusieurs ganglions lymphatiques ilio-sacrés. Des informations sur le signalement, les anomalies hématologiques, les résultats de la tomodensitométrie abdominale ou de l’échographie, le nombre et la taille des ganglions élargis, les complications peropératoires et postopératoires, le traitement et les résultats ont été recueillis.Le taux global de complications associées à la lymphadénectomie ilio-sacrée métastatique était de 26,1 %. La seule complication peropératoire enregistrée était une hémorragie et a été rapportée dans 24 (17,6 %) chirurgies, dont 11 (45,8 %) ont reçu une transfusion sanguine. Des complications postopératoires ont été signalées dans 10,4 % des interventions chirurgicales et comprenaient la formation d’oedème (Les complications associées à la lymphadénectomie ilio-sacrée pour l’adénocarcinome métastatique des glandes apocrines des sacs anaux sont relativement fréquentes et concernent principalement l’hémorragie. Ces complications sont significativement associées à la taille des ganglions lymphatiques métastatiques retirés.Cette étude rétrospective fournit des informations au clinicien concernant les complications chirurgicales potentielles pour le retrait des ganglions lymphatiques ilio-sacrés métastatiques. Ces complications, bien que rares, peuvent être graves et doivent être discutées avec les propriétaires avant la chirurgie.(Traduit par D

In collaboration with the American College of Veterinary Radiology

The lymphatic system is the first site of metastasis for most tumors and is a common reason for the failure of cancer therapy. The lymphatic system's anatomical properties make it difficult to deliver chemotherapy agents at therapeutic concentrations while avoiding systemic toxicity. Carbon nanoparticles offer a promising alternative for identifying and transporting therapeutic molecules. The larger diameter of lymphatic vessels compared to the diameter of blood vessels, allows carbon nanoparticles to selectively enter the lymphatic system once administered subcutaneously. Carbon nanoparticles stain tumor-draining lymph nodes black following intratumoral injection, making them useful in sentinel lymph node mapping. Drug-loaded carbon nanoparticles allow higher concentrations of chemotherapeutics to accumulate in regional lymph nodes while decreasing plasma drug accumulation. The use of carbon nanoparticles for chemotherapy delivery has been associated with lower mortality, fewer histopathology changes in vital organs, and lower serum concentrations of hepatocellular enzymes. This review will focus on the ability of carbon nanoparticles to target the lymphatics as well as their current and potential applications in sentinel lymph node mapping and oncology treatment regimens. This article is categorized under: Implantable Materials and Surgical TechnologiesNanoscale Tools and Techniques in Surgery.

OBJECTIVE To evaluate gastrointestinal injury and outcomes between dogs treated with immediate surgical intervention vs those treated with delayed surgical intervention for gastrointestinal foreign body obstruction (GIFBO). STUDY DESIGN Retrospective cohort study. SAMPLE POPULATION Client-owned dogs (n = 855) from five referral hospitals. METHODS Medical records of dogs in which GIFBO had been diagnosed between 2007 and 2017 were reviewed for preoperative management, timing of surgery, intraoperative findings, postoperative management, outcome, and survival. Surgical intervention was classified as immediate when it occurred within 6 hours of presentation and delayed when it occurred >6 hours after presentation. RESULTS Outcomes did not differ between dogs treated immediately (n = 584) or over 6 hours after presentation (n = 210). Intestinal necrosis and perforations were more common when surgery was delayed (P = .008; P = .019) but became nonsignificant after controlling for preoperative differences. Risk factors for necrosis and perforations included duration of clinical signs, increased lactate, linear foreign material, and timing of surgery. Enterectomies (P = .004) as well as the duration of surgery (P = .004) and anesthesia (P = .001) were increased when surgery was delayed. Immediate surgery was associated with earlier return to feeding (P = .004) and discharge from the hospital (P

Mitragynine is the most abundant psychoactive alkaloid derived from the leaves of Mitragyna speciosa (kratom), a tropical plant indigenous to regions of Southeast Asia. Mitragynine displays a moderate affinity to opioid receptors, and kratom is often self-prescribed to treat pain and/or opioid addiction. The purpose of this study was to investigate the safety and pharmacokinetic properties of mitragynine in the dog. Single dose oral (5 mg/kg) and intravenous (0.1 mg/kg) pharmacokinetic studies of mitragynine were performed in female beagle dogs. The plasma concentrations of mitragynine were measured using ultra-performance liquid chromatography coupled with a tandem mass spectrometer, and the pharmacokinetic properties were analyzed using non-compartmental analysis. Following intravenous administration, mitragynine showed a large volume of distribution (Vd, 6.3 ± 0.6 L/kg) and high clearance (Cl, 1.8 ± 0.4 L/h/kg). Following oral mitragynine dosing, first peak plasma (Cmax, 278.0 ± 47.4 ng/mL) concentrations were observed within 0.5 h. A potent mu-opioid receptor agonist and active metabolite of mitragynine, 7-hydroxymitragynine, was also observed with a Cmax of 31.5 ± 3.3 ng/mL and a Tmax of 1.7 ± 0.6 h in orally dosed dogs while its plasma concentrations were below the lower limit of quantification (1 ng/mL) for the intravenous study. The absolute oral bioavailability of mitragynine was 69.6%. Administration of mitragynine was well tolerated, although mild sedation and anxiolytic effects were observed. These results provide the first detailed pharmacokinetic information for mitragynine in a non-rodent species (the dog) and therefore also provide significant information for allometric scaling and dose predictions when designing clinical studies.

OBJECTIVE To report the clinical outcomes of the use of acellular fish skin grafts (FSGs) for the management of complex soft tissue wounds of various etiologies in dogs and cats. ANIMALS 13 dogs and 4 cats with complex wounds treated with FSGs between February 2019 and March 2021. PROCEDURES Medical records were reviewed for information regarding cause, location, size of the wound, management techniques, complications, and clinical outcomes. RESULTS In dogs, the number of FSG applications ranged from 1 to 4 (median, 2 graft applications). The time between each application ranged from 4 to 21 days (median, 9.5 days). Time to application of the first FSG ranged from 9 to 210 days (median, 19 days). Wounds closed by second-intention healing following the first fish skin application between 26 and 145 days (median, 71 days; n = 12). In cats, 1 or 2 FSGs were used, and the wounds of 3 of 4 cats healed completely by secondary intention. The wounds of 1 dog and 1 cat did not heal. There were no adverse events attributed to the use of the FSGs. CLINICAL RELEVANCE For dogs and cats of the present study, complete healing of most wounds occurred with the use of FSGs, the application of which did not require special training, instruments, or bandage materials.

BACKGROUND AND OBJECTIVES: 7-Hydroxymitragynine (7-HMG) is an oxidative metabolite of mitragynine, the most abundant alkaloid in the leaves of Mitragyna speciosa (otherwise known as kratom). While mitragynine is a weak partial μ-opioid receptor (MOR) agonist, 7-HMG is a potent and full MOR agonist. It is produced from mitragynine by the cytochrome P450 (CYP) 3A, a drug-metabolizing CYP isoform predominate in the liver that is also highly expressed in the intestine. Given the opioidergic potency of 7-HMG, a single oral dose pharmacokinetic and safety study of 7-HMG was performed in beagle dogs. METHODS: Following a single oral dose (1 mg/kg) of 7-HMG, plasma samples were obtained from healthy female beagle dogs. Concentrations of 7-HMG were determined using ultra-performance liquid chromatography coupled with a tandem mass spectrometer (UPLC-MS/MS). Pharmacokinetic parameters were calculated using a model-independent non-compartmental analysis of plasma concentration-time data. RESULTS: Absorption of 7-HMG was rapid, with a peak plasma concentration (C(max), 56.4 ± 1.6 ng/mL) observed within 15 min post-dose. In contrast, 7-HMG elimination was slow, exhibiting a mono-exponential distribution and mean elimination half-life of 3.6 ± 0.5 h. Oral dosing of 1 mg/kg 7-HMG was well-tolerated with no observed adverse events or significant changes to clinical laboratory tests. CONCLUSIONS: These results provide the first pharmacokinetic and safety data for 7-HMG in the dog, and therefore contribute to the understanding of the putative pharmacological role of 7-HMG resulting from an oral delivery of mitragynine from kratom.

Pediatric gastroenterology (GI) is an exciting field of digestive functions and the diseases that affect them in children. This chapter will discuss the fundamentals of a GI fellowship and how to decide if it is the career for you. Additionally, it will touch upon how to find the program that will best fit your needs. Read on to learn more about pediatric GI fellowship training.

The purpose of this retrospective study was to compare outcome measures in dogs treated by a primary care veterinarian (pcDVM) before referral and after seeking collaboration with a board-certified veterinary dermatologist (BCVD) for cases of severe recurrent chronic otitis externa. Medical records of 65 client-owned dogs were retrospectively reviewed, and data were obtained regarding treatment history, referral timeframe, recurrence rate, clinical signs, and resolution of signs. The median number of otitis recurrences while under the care of the pcDVM was 4 (range 1–40) versus collaborative BCVD care of 2 (P < .01). There was a longer median time to otitis recurrence with collaborative care (171 days) compared with dogs managed by the pcDVM before referral (21 days; P > .01). Proliferative changes in the ear canals improved in 41/45 (91%) of cases under BCVD care compared with 6/45 (13%) under care by the pcDVM (P < .01). Dogs with chronic otitis had better long-term outcomes when collaboration with a BCVD was pursued within 6 mo of treatment. Referral or consultation with a BCVD should be considered for cases of chronic canine otitis that are persistent or quickly recurrent (20–30 days) over a 6 mo period.

This document establishes safety guidelines for physicians, nurses, and allied health care and facility staff who may be exposed to patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a health care facility. SARS-CoV-2 infection is highly contagious and places health care workers at risk for infection resulting in coronavirus disease (COVID-19). Physicians, nurses, and allied health care and facility staff in all frontline environments must be provided and utilize necessary personal protective equipment (PPE). It is important that health care staff adopt a universal set of guidelines in which to conduct themselves in order to minimize infection with the SARS-CoV-2 contagion. The establishment of these guidelines is necessary in this viral pandemic since such directives can create a standard of safety that is universally accepted. These guidelines establish a framework to provide consistency among health care facilities and staff from the time the staff member arrives at the health care facility until they return home. These guidelines provide a practical description of the minimum necessary protection for physicians, nurses, and allied health care and facility staff against SARS-CoV-2 infection.

OBJECTIVE To compare the efficacy of application of an alcohol-based antiseptic (80% ethyl alcohol) hand rub (ABAHR) with that of a 2% chlorhexidine gluconate scrub (CGS2) for immediate reduction of the bacterial population on the skin of dogs. ANIMALS 50 client-owned dogs with no evidence of skin disease. PROCEDURES On each dog, 2 areas of hair on the ventral aspect of the abdomen were clipped with a No. 40 blade and cleared of debris. A direct contact plate holding tryptic soy agar with polysorbate 80 and lecithin was gently pressed (for 2 seconds) on each skin site (preapplication sample). The CGS2 and ABAHR were each aseptically applied to 1 skin site on each dog. A direct contact plate was subsequently applied to each site in a similar manner (postapplication sample). All plates were cultured, and bacterial isolates were identified and quantified by the number of CFUs per plate. RESULTS Application of the CGS2 and ABAHR significantly decreased skin bacterial colony counts, compared with findings for preapplication samples. The number of CFUs per plate or postapplication percentage reduction in CFUs per plate did not differ between treatments. There were no adverse skin reactions associated with either application. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that applications of ABAHR and CGS2 were equally effective at immediately reducing the bacterial population on the skin of dogs, and there was no significant difference in percentage reduction in colony counts between the 2 applications.

Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population.Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015.Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel.In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

Background Anemia is frequently encountered in inflammatory bowel disease (IBD) with studies reporting an even greater prevalence among children (16–72%) than adults (4–67%) at any given time during disease course. Anemia is commonly a result of chronic iron deficiency (ID) and inflammation, with the two conditions often overlapping. Many studies have shown that gastroenterologists underecognize and undertreat these conditions. Moreover, there are currently no pediatric-specific guidelines. To align clinical practice with adult guideline recommendations and evidence-based publications, we developed a quality improvement (QI) initiative incorporating an algorithmic framework for recognition and treatment of iron deficiency anemia (IDA) in pediatric IBD. Methods The goals were twofold: improvement in 1) detection and 2) treatment rates of IDA in IBD patients. A multifaceted approach with a series of plan-do-study-act (PDSA) cycles was executed: 1. Public review of our current performance of anemia screening and treatment with all divisional providers (n=60) (11/2017), 2. Development of a new divisional clinical pathway for screening and treatment of IDA in patients with IBD (01/2018), 3. Educational sessions (02-04/2018), 4. Creation of an Epic order set and patient and family education (PFE) (02/2018), 5. Online availability of our pathway (11/2018), and 6. Utilization of an electronic medical record (EMR)-integrated dashboard to track our outcome metrics. A designated coordinator identified patients in the EMR and sent monthly reports to providers based on our automated dashboard which captured the percentage of patients with ordered hemoglobin (Hb) and ferritin, percentage of patients with anemia and/or iron deficiency, and percentage of patients with ordered iron therapy. Baseline data from July 2016 were compared to data after pathway implementation. Results In the pre-intervention period (July 2016-November 2017), 73.5% of our outpatient IBD population had a Hb ordered, with anemia prevalence of 36.3%. Only a minority of patients with anemia were being screened for ID (19.3%). Iron supplementation was prescribed in 38.1% of patients with documented anemia. Following the implementation of this QI initiative, rate of patients with biannual Hb testing completed increased to 80.1%, while prevalence of anemia decreased to 32.1%. Significant improvement was observed with screening and treatment rate increasing to 43.1% and 50.4% respectively by July 2019 as shown in Fig. 1–2. Notably, patients with moderate to severe anemia improved significantly from 48.7% to 62.1%. Conclusion ID and anemia are commonly underdiagnosed and undertreated in children with IBD. An evidence and expert based pathway combined with implementation of provider-based monthly reports using the EMR to support clinical decision may help increase screening and intervention and decrease rates of anemia prevalence. https://www.chop.edu/clinical-pathway

Objective To evaluate the pharmacokinetics (PK) of platinum (Pt) and safety of carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads after implantation in healthy cats. Study design In vivo experimental study. Animals Six healthy adult cats. Methods Three C-I CSH beads were implanted in muscle pockets over the right and left hemithoraces of each cat (~3.9 mg/kg of Pt; 60.4 mg/m2 of calculated carboplatin). Hematology and blood chemistry were tested at baseline and 3, 7, 14, and 21 days postimplantation. Serum was analyzed for Pt at specific times from 1 hour to 21 days. Tissue was obtained for histopathology and analysis of Pt at 3, 7, 14, and 21 days at standardized distances from implantation sites. Results Platinum was detected in tissues at all times and distances (range, 0.1-4.19 μg/g). Serum Pt increased up to 2.6 hours (3.25 μg/mL) then decreased sharply. Samples containing muscle had higher Pt compared with samples without muscle (P = .004). Mild hypercalcemia was noted in four cats, and mild inflammatory reaction was noted on histopathology of all samples. Conclusion Platinum was released from C-I CSH beads differentially into surrounding tissues over 21 days. Systemic absorption of Pt was minimal, but mild hypercalcemia occurred. Clinical significance Implantation was well tolerated by healthy adult cats. Securing beads within muscle may limit Pt diffusion to targeted tissue. Although Pt concentrations did not achieve levels reported to be cytotoxic for feline sarcoma cells in culture, results provide evidence to support evaluation of efficacy in the tumor microenvironment of cats with locally invasive cancers.

A 6 yr old Boston terrier presented with acute onset of vomiting and anuria 4 days following a caesarian section and ovariohysterectomy for treatment of dystocia. A total cystectomy with ligation of both ureters was diagnosed via exploratory laparotomy surgery. A jejunocystoplasty was performed in addition to a bilateral reimplantation of the ureters into the reconstructed bladder and proximal urethra. Postoperative complications included a retained ureteral stent, persistent pyelectasia, persistent hydroureters, recurrent urinary tract infections, and intermittent urinary incontinence. Four years postoperation, the dog is doing clinically well with intermittent urinary incontinence and periodic urinary tract infections. Jejunocystoplasty with bilateral ureteral reimplantation should be considered as a treatment option for dogs following total cystectomy that occurred because of a surgical error. Owners should be informed of potential complications prior to surgery.

BACKGROUND Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there is limited pediatric data. This study aimed to describe the adverse events and clinical response to vedolizumab in refractory pediatric IBD. METHODS Disease activity indices, clinical response, concomitant medication use, and adverse events were measured over 22 weeks in an observational prospective cohort study of children with refractory IBD who had failed anti-tumor necrosis factor therapy and subsequently initiated vedolizumab therapy. RESULTS Twenty-one subjects, 16 with Crohn disease, received vedolizumab. Clinical response was observed in 6/19 (31.6%) of the evaluable subjects at week 6 and in 11/19 (57.9%) by week 22. Before induction, 15/21 (71.4%) participants were treated with systemic corticosteroids, as compared with 7/21 (33.3%) subjects at 22 weeks. Steroid-free remission was seen in 1/20 (5.0%) subjects at 6 weeks, 3/20 (15.0%) at 14 weeks, and 4/20 (20.0%) at 22 weeks. There was statistically significant improvement in serum albumin and hematocrit; however, C-reactive protein increased by week 22 (P < 0.05). There were no infusion reactions. Vedolizumab was discontinued in 2 patients because of severe colitis, requiring surgical intervention. CONCLUSIONS There is limited experience with vedolizumab therapy in pediatric IBD. There seems to be a marked number of subjects with clinical response in the first 6 weeks that increases further by week 22 despite the severity of disease in this cohort. Adverse events may not be directly related to vedolizumab. This study is limited by small sample size, and larger prospective studies are warranted.

OBJECTIVE To characterize spatial release of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads by use of an agarose tissue phantom. SAMPLE 3-mm-diameter beads (n = 60) containing 4.6 mg of carboplatin (2.4 mg of platinum)/bead. PROCEDURES 18 L of 1% agarose was prepared and poured into 36 containers (10 × 10 × 10 cm), each of which was filled half full (0.5 L/container). After the agarose solidified, 1, 3, 6, or 10 CI-CSH beads were placed on the agar in defined patterns. An additional 36 blocks of agar (0.5 L/block) were placed atop the beads, positioning the beads in the center of 1 L of agar. The experiment was replicated 3 times for each bead pattern for 24, 48, and 72 hours. At these times, representative agarose blocks were sectioned in the x-, y-, and z-planes and labeled in accordance with their positions in shells radiating 1, 2, 3, 4, and 5 cm from the center of the blocks. Agarose from each shell was homogenized, and a sample was submitted for platinum analysis by use of inductively coupled plasma–mass spectroscopy. RESULTS Platinum diffused from CI-CSH beads at predicted anticancer cytotoxic concentrations for 2 to 5 cm. CONCLUSIONS AND CLINICAL RELEVANCE Results provided information regarding the spatial distribution of platinum expected to occur in vivo. Agarose may be used as a diffusion model, mimicking the characteristics of subcutaneous tissues. Measured platinum concentrations might be used to guide patterns for implantation of CI-CSH beads in animals with susceptible neoplasms.

Since 2008, the American Heartworm Society has recommended using a three-dose melarsomine protocol (a single intramuscular injection of melarsomine dihydrochloride at 2.5mg/kg, followed approximately 1 month later with two doses administered 24h apart) for all heartworm-positive dogs, with doxycycline given at 10mg/kg twice daily for 4 weeks prior to administration of melarsomine. To report the efficacy and side effects of this standard heartworm treatment protocol in 50 dogs presenting to our hospital from 2008 to 2011, information on the history, clinical, laboratory, and diagnostic imaging findings and treatment was obtained from medical records. When possible, additional follow-up information was obtained through telephone interviews with referring veterinarians and owners. Twenty-six dogs (52%) experienced minor complications, such as injection site reactions, gastrointestinal signs (vomiting, diarrhea, inappetance), and behavioral changes (lethargy, depression) during or after heartworm treatment. Twenty-seven dogs (54%) experienced respiratory signs (coughing, dyspnea) and heart failure attributed to progressive heartworm disease and worm death. Seven dogs (14%) died within the treatment period. Owners frequently reported behavioral changes, such as depression and lethargy, suspected to be secondary to pain. Fifty percent of owners surveyed indicated that, prior to the diagnosis, they either were not currently administering heartworm preventative, or they had recently adopted the dog from a shelter that did not administer preventatives. After treatment, 100% were administering heartworm preventatives to their pet. Eighteen dogs (36%) received a heartworm antigen test 6 months after adulticide therapy, 12 of which tested negative and six tested positive. Four of the dogs with a positive test at 6 months had negative tests 1 month later with no additional treatment. Adverse effects were common with the recommended protocol, but the majority of these were mild. Dogs in Class 1 (i.e., heartworm positive but otherwise largely lacking clinical evidence of disease) did not experience any major adverse effects or death.

Objective To determine the in vitro chemosensitivity of feline injection site-associated sarcoma (FISAS) cells to carboplatin concentrations generated by elution of carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads. Study design In vitro study. Sample Five immortalized cell lines from histologically confirmed, primary FISASs. Methods For each cell line, one 96-well microplate was used for each time point (24, 48, 72 hours). In each microplate, 3 wells were seeded with ∼7.5 × 103 cells per well for every carboplatin treatment added, ranging from 5 to 450 µM. Microculture plates were incubated for 24, 48, or 72 hours. Drug efficacy was assessed via a bioreductive fluorometric assay. For apoptosis analysis, 3 wells were seeded with ∼5 × 104 cells per well for every carboplatin treatment added, ranging from 5 to 450 µM. Flow cytometry was performed and the relative percentages of viable, apoptotic, and late apoptotic/necrotic cells were reported. All experiments were run in triplicates. Results Carboplatin exerted dose-dependent and time-dependent effects on FISAS cell viability. The IC50 values were within the range of carboplatin concentrations eluted from CI-CSH beads. Conclusion Elution of carboplatin from CI-CSH beads generate concentrations sufficient to result in 50% growth inhibition of FISAS cells in vitro. Local tumor control might be achieved by implantation of CI-CSH beads immediately following radical or marginal excision of the primary tumor or by implantation without tumor resection.

Complex inflammatory bowel disease (IBD) including fistulizing or penetrating Crohn disease (CD) and fulminant ulcerative colitis (UC) can lead to serious complications including abscess, fistula, perforation, obstruction, and toxic megacolon which require collaboration between the gastroenterologist and surgeon. Prompt diagnosis of these entities will allow for medical optimization and surgical intervention, if required. This chapter will describe the evaluation for patients with suspected intra-abdominal complications of CD and considerations for management, with a focus on intra-abdominal and pelvic abscess resulting from internal penetrating disease. In particular, medical and surgical options for treatment will be compared. Surgical emergencies and elective procedures in CD for the indications of perforation, obstruction, and stricture will be briefly reviewed. The surgical treatment of UC is the focus of Chap. 42, but the complication of toxic megacolon will also be described here.

Chondrocytes possess the capacity to transduce load-induced mechanical stimuli into electrochemical signals. The aim of this study was to functionally characterize an ion channel activated in response to membrane stretch in isolated primary equine chondrocytes. We used patch-clamp electrophysiology to functionally characterize this channel and immunohistochemistry to examine its distribution in articular cartilage. In cell-attached patch experiments, the application of negative pressures to the patch pipette (in the range of 20-200 mmHg) activated ion channel currents in six of seven patches. The mean activated current was 45.9 +/- 1.1 pA (n = 4) at a membrane potential of 33 mV (cell surface area approximately 240 microm(2)). The mean slope conductance of the principal single channels resolved within the total stretch-activated current was 118 +/- 19 pS (n = 6), and reversed near the theoretical potassium equilibrium potential, E(K+), suggesting it was a high-conductance potassium channel. Activation of these high-conductance potassium channels was inhibited by extracellular TEA (K(d) approx. 900 microM) and iberiotoxin (K(d) approx. 40 nM). This suggests that the current was largely carried by BK-like potassium (MaxiK) channels. To further characterize these BK-like channels, we used inside-out patches of chondrocyte membrane: we found these channels to be activated by elevation in bath calcium concentration. Immunohistochemical staining of equine cartilage samples with polyclonal antibodies to the alpha1- and beta1-subunits of the BK channel revealed positive immunoreactivity for both subunits in superficial zone chondrocytes. These experiments support the hypothesis that functional BK channels are present in chondrocytes and may be involved in mechanotransduction and chemotransduction.

Postcolonial criticism generally has not had a strong history of engaging with environmental or ecological discourses but the prospect of global warming is likely to change this. It is likely to be particularly significant for postcolonial literary criticism, a discipline that in recent years has struggled to make itself relevant to the task of opposing globalisation. Some postcolonial literary critics have already begun using the arguments and concepts drawn from environmental discourses and eco criticism, and in doing so they have contributed powerfully to the postcolonial critique of globalisation; however, to date few postcolonial critics have thought to use these same arguments and concepts to analyse fictions that speculate on the social effects of global warming. Taking a short story by a leading Australian author that is set in the year 2035, the last half of the article sets out to demonstrate the political potential of such a critical approach and the value of reading apocalyptic speculative fictions in particular.

To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101. By 19 passages, an escape mutant emerged with a >20,000-fold resistance to AD101. This virus was cross-resistant to a related inhibitor, SCH-C, and partially resistant to RANTES but still sensitive to CCR5-specific mAbs. The resistant phenotype was stable; the mutant virus retained AD101 resistance during nine additional passages of culture in the absence of inhibitor. Replication of the escape mutant in peripheral blood mononuclear cells completely depended on CCR5 expression and did not occur in cells from CCR5-Δ32 homozygous individuals. The escape mutant was unable to use CXCR4 or any other tested coreceptor to enter transfected cells. Acquisition of CXCR4 use is not the dominant in vitro escape pathway for a small molecule CCR5 entry inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the inhibitor, first by requiring lower levels of CCR5 for entry and then probably by using the drug-bound form of the receptor.

Objective: To evaluate if addition of educational cartoon to pediatric bowel preparation instructions improves the quality of bowel preparation and patient experience. Methods: Patients were randomized to control group receiving standard bowel preparation instructions or intervention group receiving additional educational cartoon. To objectively rate bowel preparation, a blinded endoscopist completed numeric Ottawa score (0-14, with 0 being best). The family also completed a questionnaire rating the bowel preparation process. Results: Data from 23 patients were analyzed. Mean Ottawa score in the intervention group compared with controls was not significantly different (mean scores 3.73 and 3.33, respectively; P = .384). Level of education was significantly correlated with better Ottawa score in the overall population (ρ = −.462, P = .026) and within the control group (ρ = −.658, P = .02). Both groups of patients reported positive experience with bowel preparation. Conclusion: There may be benefit to further investigation of this educational cartoon in parents with less than college level education or non-English-speaking families in larger population of patients.

HIV-1 entry into CD4+cells requires the sequential interactions of the viral envelope glycoproteins with CD4 and a coreceptor such as the chemokine receptors CCR5 and CXCR4. A plausible approach to blocking this process is to use small molecule antagonists of coreceptor function. One such inhibitor has been described for CCR5: the TAK-779 molecule. To facilitate the further development of entry inhibitors as antiviral drugs, we have explored how TAK-779 acts to prevent HIV-1 infection, and we have mapped its site of interaction with CCR5. We find that TAK-779 inhibits HIV-1 replication at the membrane fusion stage by blocking the interaction of the viral surface glycoprotein gp120 with CCR5. We could identify no amino acid substitutions within the extracellular domain of CCR5 that affected the antiviral action of TAK-779. However, alanine scanning mutagenesis of the transmembrane domains revealed that the binding site for TAK-779 on CCR5 is located near the extracellular surface of the receptor, within a cavity formed between transmembrane helices 1, 2, 3, and 7.

We have studied the mechanisms by which the CC-chemokine RANTES can enhance the infectivities of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, when present at concentrations in excess of 500 ng/ml in vitro. Understanding the underlying mechanisms might throw light on fundamental processes of viral infection, in particular for HIV-1. Our principal findings are twofold: firstly, that oligomers of RANTES can cross-link enveloped viruses, including HIV-1, to cells via glycosaminoglycans (GAGs) present on the membranes of both virions and cells; secondly, that oligomers of RANTES interact with cell-surface GAGs to transduce a herbimycin A-sensitive signal which, over a period of several hours, renders the cells more permissive to infection by several viruses, including HIV-1. The enhancement mechanisms require that RANTES oligomerize either in solution or following binding to GAGs, since no viral infectivity enhancement is observed with a mutant form of the RANTES molecule that contains a single-amino-acid change (glutamic acid to serine at position 66) which abrogates oligomerization.

NIMH Genetics Initiative Bipolar Group: John I. Nurnberger, Jr.* (Chair), J. Raymond DePaulo,Elliot S. Gershon, Theodore Reich, Mary C. Blehar, and collaborators from Indiana University(Howard J. Edenberg, Tatiana Foroud, Marvin Miller, Elizabeth Bowman, Aimee Mayeda, N. LeelaRau, Carrie Smiley, and P. Michael Conneally), Johns Hopkins University (Francis Mc-Mahon, Deborah Meyers, Sylvia Simpson, Melvin McInnis, and O. Colin Stine), NIMH IntramuralResearch Program (Sevilla Detera-Wadleigh, Lynn Goldin, Juliet Guroff, Elizabeth Max-well, Diane Kazuba, Pablo V. Gejman, Judith Badner, and Alan Sanders), and WashingtonUniversity of St. Louis (John Rice, Laura Bierut, and Alison Goate).Four sites collaborated with the NIMH todevelop a resource for the genetic study ofbipolar (BP) illness. Common methods of as-certainment and assessment were devel-oped in 1989. A series of families with a bi-polar I (BPI) proband and at least one BPIor schizoaffective, bipolar type (SA/BP)first-degree relative has been studied. Wenow report initial data from a genomic sur-vey with an average intermarker interval of10 cM on 540 subjects from 97 families. Thisis the largest commonly ascertained and as-sessed linkage sample for bipolar illness re-ported to date; it includes 232 subjects withBPI, 32 SA/BP, 72 bipolar II (BPII), and 88unipolar, recurrent (UPR). Nonparametricmethods of analysis were employed, with allsites using affected sib pair analysis. Thestrongest findings thus far appear to be onchromosomes 1, 6, 7, 10, 16, and 22. Supporthas also been found for some previously re-ported linkages, including 21q and possiblyXq26. All these areas (as well as others) willbe followed up with additional markers andfurther analyses. No locus tested thus farmeets stringent criteria for an initial find-ing of significant linkage. Am. J. Med. Genet.74:227–237, 1997.