Dolichocolon (redundant colon) in a rhesus macaque (Macaca mulatta).

Dolichocolon (redundant colon) is an underdiagnosed cause of severe constipation in humans. The clinical presentation reported here in a rhesus macaque closely resembles that of intestinal adenocarcinoma, the most common neoplasia in macaques. Dolichocolon should be considered in differential diagnosis of macaques with anorexia, weight loss, and constipation.

Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates.

Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L- CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.

A Large Segmental Mid-Diaphyseal Femoral Defect Sheep Model: Surgical Technique.

Background:There are numerous animal models available to study bone healing as well as test strategies to accelerate bone formation. Sheep are commonly used for evaluation of long bone fractures due to similar dimensions and weight bearing environments compared to patients. Large critical-size defects can be created in sheep to facilitate the study of implantable materials, osteogenic proteins, and stem cell treatments. Studies have been published using plates to stabilize large critical size defects in femoral, tibial, and metatarsal defects. External fixators have also been used to stabilize tibial defects in sheep.Methods: The purpose of the current paper is to detail the surgical technique for creation of a 42 mm mid-diaphyseal femoral defect stabilization with an intramedullary device in sheep. Additional surgical details are provided for dynamization, reverse dynamization, and device removal.Conclusion: The article provides multiple technical tips applicable to this and other ovine osteotomy models and concludes with a discussion comparing the use of each stabilization technique in clinically significant large critical-size bone defects.

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Mice.

Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate plane of analgesia. An alternative formulation that provides prolonged plasma concentration with long-lasting effects would be beneficial in achieving steady-state analgesia. We evaluated a long-lasting and highly concentrated formulation of buprenorphine (Bup-LHC) in mice. Pharmacokinetic analysis was performed to assess plasma concentrations in male C57BL/6J (B6) and female CD1 mice after subcutaneous injection of 0.9 mg/kg. The Bup-LHC formulation provided plasma drug levels that exceeded the therapeutic level for at least 12 h in male B6 mice and was below therapeutic levels by 8 h in female CD1 mice. An experimental laparotomy model was used to assess analgesic efficacy. Female CD1 mice were treated with either Bup-LHC (0.9 mg/kg) or saline at 1 h before undergoing an ovariectomy via a ventral laparotomy. At 3, 6, 12, 24, and 48 h after surgery, pain was assessed based on the following behaviors: orbital tightness, grooming, wound licking, rearing, arched posture, ataxia, piloerection, nest building, and general activity. At 3 and 6 h after surgery, Bup-LHC-treated mice had significantly less wound licking and orbital tightness and considerably higher activity levels than did saline-treated mice. At 12 h, wound licking, orbital tightness and activity in Bup-LHC-treated mice were no longer significantly different from those of saline-treated mice. The results of this study suggest that Bup-LHC at 0.9 mg/kg provides sufficient plasma concentrations for analgesia in mice for 6 to 12 h after administration, as demonstrated behaviorally for at least 6 h after surgery.

Distributed stimulation increases force elicited with functional electrical stimulation.

OBJECTIVE: The maximum muscle forces that can be evoked using functional electrical stimulation (FES) are relatively modest. The reason for this weakness is not fully understood but could be partly related to the widespread distribution of motor nerve branches within muscle. As such, a single stimulating electrode (as is conventionally used) may be incapable of activating the entire array of motor axons supplying a muscle. Therefore, the objective of this study was to determine whether stimulating a muscle with more than one source of current could boost force above that achievable with a single source. APPROACH: We compared the maximum isometric forces that could be evoked in the anterior deltoid of anesthetized monkeys using one or two intramuscular electrodes. We also evaluated whether temporally interleaved stimulation between two electrodes might reduce fatigue during prolonged activity compared to synchronized stimulation through two electrodes. MAIN RESULTS: We found that dual electrode stimulation consistently produced greater force (~50% greater on average) than maximal stimulation with single electrodes. No differences, however, were found in the fatigue responses using interleaved versus synchronized stimulation. SIGNIFICANCE: It seems reasonable to consider using multi-electrode stimulation to augment the force-generating capacity of muscles and thereby increase the utility of FES systems.

Silicon Foreign Body in the Cerebrum of a Rhesus Macaque (Macaca mulatta).

A male rhesus macaque with a cephalic chamber implant for neurophysiology recording presented with hemiparesis affecting the left thoracic and pelvic limbs at approximately 5 wk after craniotomy surgery. MRI indicated a 1×2-cm ovoid cerebrocortical cystic lesion immediately subjacent to the right hemisphere craniotomy and recording chamber. Transdural aspiration of sterile transudate and resultant decompression resolved the hemiparesis, and follow-up MRI at 1 mo indicated resolution of the lesion. Subsequently, necropsy at study end revealed a cerebrocortical foreign body composed of silicon. The atypically slow cure rate of the lot of silicon used and the unique recording chamber configuration were underlying factors that contributed to the formation of this foreign body. To our knowledge, this report is the first description of iatrogenic intracerebral foreign body in a macaque.

Supernumerary Incisors in CB6F1 Mice Conditioned with Chemotherapy and Total Body Irradiation before Bone Marrow Transplantation.

Multiple adult female CB6F1 mice presented with supernumerary incisors after preconditioning with chemotherapy and total body irradiation for bone marrow transplantation (BMT). Mice received nonmyeloablative total body irradiation (3 Gy) and either cyclophosphamide or bendamustine, followed by BMT and posttransplantation cyclophosphamide or bendamustine. Here we describe the clinical presentation, µCT findings, and histopathologic evaluation of the affected mice. These analyses confirmed the gross diagnosis and revealed details of the abnormal tooth morphology. We surmise that the combination of total body irradiation and chemotherapy resulted in the abnormal formation of supernumerary incisors. Supernumerary teeth should be considered as a potential confounding factor in tracking weight loss after BMT. These conditions can be managed to allow animals to reach their intended scientific endpoint.

Well-differentiated Liposarcoma in a Bonnet Macaque (Macaca radiata).

Here we describe the occurrence of a subcutaneous liposarcoma in a geriatric bonnet macaque (Macaca radiata). Clinical presentation was a rapidly growing, ulcerated, subcutaneous mass in the umbilical region of a 28-y-old intact female macaque. The mass was successfully removed through excisional biopsy, and histopathology provided a morphologic diagnosis of well-differentiated liposarcoma. The macaque recovered without complication and displayed no signs of recurrence for at least 18 mo after excision. To our knowledge, this case represents the first report of liposarcoma in a bonnet macaque.

Electrocardiogram abnormalities in captive chimpanzees (Pan troglodytes).

Although cardiovascular disease is the leading cause of death in the captive chimpanzee population, little is known about the prevalence and etiology of heart disease in this species. We reviewed the physical exam records of 265 common chimpanzees (Pan troglodytes) for electrocardiogram abnormalities. During the 24-mo period reviewed (August 2003 through August 2005), 34 animals were diagnosed with cardiac arrhythmias consisting of ventricular arrhythmias, supraventricular arrhythmias, conduction disturbances, mixed arrhythmias, and bradycardia. The incidence of cardiac arrhythmia was significantly higher in male animals, chimpanzees 20 to 39 y old, and those with structural heart disease. Incidence of cardiac arrhythmia was not significantly higher in animals with hypertension, hyperlipidemia, or chronic viral infections. During the retrospective period, 7 animals with cardiac arrhythmias died or were euthanized. Mortality was significantly higher in animals with ventricular arrhythmias compared with those without ventricular arrhythmias. We conclude that in the common chimpanzee, age, male gender, and structural heart disease are risk factors for developing cardiac arrhythmias and that ventricular arrhythmias are risk factors for mortality.

Successful treatment of idiopathic dilated cardiomyopathy in an adult chimpanzee (Pan troglodytes).

Various congenital and acquired forms of heart disease have been reported in captive lowland gorillas, and heart disease is a major cause of morbidity and mortality in geriatric humans. However, the prevalence of heart disease is unknown in nonhuman great apes species. Indeed, little is known about heart disease in chimpanzees, although the species has been used in research for decades. This report details the clinical presentation and diagnostics (thoracic radiography, electrocardiography, and echocardiography) utilized to diagnose idiopathic dilated cardiomyopathy in a 27-year-old male chimpanzee. Treatment decisions--indicated by follow-up diagnostics including repeat electrocardiography, echocardiography, and clinical laboratory data--over the 22-month period during which he continues to be treated are described. In addition, electrocardiographic and echocardiographic findings obtained from 20 clinically normal adult (11 female and 9 male) chimpanzees are presented for comparison.

Dry bedding provides cost-effective enrichment for group-housed rhesus macaques (Macaca mulatta).

Dry bedding has been shown to be an effective enrichment strategy for small groups of captive nonhuman primates housed in cages or in small enclosures with concrete flooring. However, dry bedding is used infrequently for large groups because of the perception that its use is time- and resource-intensive. We investigated the cost-effectiveness of this enrichment strategy in large groups (30 to 50 subjects) of rhesus macaques. Macaques were housed under 3 comparison conditions for 4 wk: pine shavings (n = 4), aspen and pine shaving mixture (n = 4), and nonbedded control (n = 4). As measures of resource consumption, husbandry tasks were documented by using time-in-motion methodology, and water usage was determined. In addition, groups underwent behavioral observations to assess the effect of dry bedding. The time required to care for units did not differ between bedded and nonbedded units. However, significantly less water was used for sanitization of bedded compared with nonbedded units. Monkeys housed in bedded units showed more foraging (13.8% ± 1.6% of time in bedded compared with 4.0% ± 0.3% of time in nonbedded units) and less aggression and self-grooming. Dry bedding benefited the macaques, reduced water usage and costs, and did not affect human resources.

Diagnosis and treatment of pulmonary arterial hypertension and atrial fibrillation in an adult chimpanzee (Pan troglodytes).

This report describes the diagnosis and treatment of pulmonary arterial hypertension (PAH) in an adult male captive chimpanzee. Although cardiovascular disease in general is common in human and great apes, diagnosis and treatment of PAH in nonhuman primates are uncommon. In the case we present, the adult chimpanzee was diagnosed with an arrhythmia during an annual physical examination and later with PAH during a scheduled cardiovascular evaluation. PAH can either be primary or secondary and can lead to right ventricular overload and heart failure. This description is the first case study of pulmonary arterial hypertension in a great ape species.