Comparative Medicine - LABSG



Comparative Medicine

Volume 66, Number 2, April 2016

ORIGINAL RESEARCH

Mouse Models

Peterson et al. Biodistribution Analyses of a Near-Infrared, Fluorescently Labeled, Bispecific Monoclonal Antibody Using Optical Imaging, pp. 90-99

 

Domain 3: Research (K2 Research Methods and Equipment)

 

SUMMARY: Bispecific antibodies, which recognize 2 different epitopes on the same or different cells or other biologic material, have been used to treat various diseases and conditions in medical application. Reaching two targets at once holds benefits over monoclonal targets, but the size of a bispecific protein results in differing distribution, filtration and pharmacokinetics of these materials which must be validated in animal models prior to application in pharmaceutical development.

This paper describes the application of fluorescent antibody tags (Alexa Fluor 750 and 680) attached to an antibody which concurrently tags insulin-like growth factor 1 (IGF1R) and epidermal growth factor receptor (EGFR). The resulting antibody (and nonspecific controls) were administered to female athymic nu/nu mice bearing NCI-H358 nonsmall-cell lung carcinoma tumors at 1000mm^3 in volume via tail vein and imaged using in vivo fluorescent imaging modalities.  While ex vivo labeling of tumor cells with the fluorescent markers resulted in accurate detection of the tumor marker targets (compared to controls), the in vivo imaging indicated fluorescence primarily in the liver, kidney, and background levels in the stomach, while tumor fluorescence was nonspecific compared to control antibody. The fluorescent label was also rapidly detecting in rising amounts in the urinary bladder, suggesting rapid processing and excretion rather than retention in the tumor.  This in vivo imaging may be effective in assessing pharmacokinetics during development of therapeutic agents; determination that agents are not arrived/retained by the desired targets provides added information over ex vivo analyses.

 

QUESTIONS

1.   What is the Fc fragment of an antibody?

2.  Where might you find Fc receptors?

3.  What does the acronym IVIS stand for, when referring to imaging?

 

ANSWERS

1.   The “crystallizable fragment” arises from the heavy chain constant region of the immunoglobulin/antibody.  The Fc fragment cannot bind an antigen epitope, but is responsible for the effector functions of antibodies such as complement fixation, and is recognized by Fc receptors on cellular surfaces.

2.  Fc receptors are found on many immune cell surfaces, including B lymphocytes, dendritic cells, macrophages, neutrophils, and mast cells. Binding of Fc receptors typically stimulates phagocytosis and/or cytotoxic reactions (ADCC), as well as triggering downstream mechanisms of activated immunity.

3.  IVIS = in vivo imaging system, which allows survival imaging of live animals, often used for longitudinal studies using the same individuals.

 

Michaud et al. Comparison of 3 Topical Treatments against Ulcerative Dermatitis in Mice with a C57BL/6 Background, pp. 100-104

Domain 1: Management of Spontaneous and Experimentally Induced Diseases and Conditions

Task 4

SUMMARY: Ulcerative dermatitis (UD) is a common condition in C57BL/6 mice and strains with this background. The etiology of UD is unclear but appears to have a genetic component associated with the C57BL/6 strain and has been reported as secondary to a variety of conditions. Treatment is unrewarding, resulting in euthanasia in many cases.

In the present study they compared 3 topical treatments against spontaneous UD in mice with a C57BL/6 background. In total, 301 mice of both sexes were included in this study, and the tested treatments comprised:

1.  Bacitracin-neomycin sulfate-polymixin B sulfate ointment twice daily,

2.  10% povidone-iodine ointment plus 1% silver sulfadiazine cream once daily, and

3.   0.005% sodium hypochlorite once daily.

Lesion healing was defined as complete skin reepithelialization with orwithout hair regrowth. Sex, age, lesion location, and type and length of treatment were analyzed by using univariate and multivariate logistic regression. Of the 79 mice treated with triple-antibiotic ointment, 27 (34%) healed, compared with 43 of the 125 (34%) treated with povidone-iodine and sulfadiazine and 69 of the 97 (71%) treated with hypochlorite. Lesion size and treatment with 0.005% sodium hypochlorite were the only significant predictors of healing; all other variables were not statistically significant in multivariate analysis. They conclude that 0.005% sodium hypochlorite is an effective topical treatment alternative for UD in C57BL/6 mice and strains on this background, and a favorable prognosis depends on the early identification and treatment of those lesions.

QUESTIONS

1. Ulcerative dermatitis (UD) is a common condition in C57BL/6 mice and strains with this background. The etiology of UD is?

a.  Allergies

b.  Infection

c.  Genetic

d.   Unclear

2.  Among topical treatments listed below which one has been shown to be most effective in treating UD?

a.  Caladryl lotion

b.  Chlorhexidine

c.  Cyclosporine

d.  Toenail trimming

3.  T/F. Flank lesions had a worst outcome of healing than did all other locations combined.

4. Which of the following treatments were found to be the most effective?

a.  10% povidone-iodine ointment plus 1% silver sulfadiazine cream once daily

b.  0.005% sodium hypochlorite

c. Bacitracin-neomycin sulfate-polymixin B sulfate ointment twice daily

d.  No difference

ANSWERS

1. d. Unclear

2. c. Cyclosporine

3. True

4. 0.005% sodium hypochlorite

Kohnken and Schwahn. Lack of Chronic Histologic Lesions Supportive of Sublethal Spontaneous Seizures in FVB/N Mice, pp. 105-111

Primary Species: Mouse (Mus musculus)

Domain 3: Research; K3 - Animal Models and Normal Biology of Common Strains

SUMMARY

Background

• Seizures:

o   Naturally occurring seizure activity frequently originates in the hippocampus and occurs through a common excitatory pathway that includes glutaminergic neuronal depolarization, resulting in a massive influx of calcium into the cell and cell death

o   Excitotoxic induced seizures are mediated by glutamate, leading to cell death in the CA1 and CA3 regions of the hippocampus, amygdala, piriform cortex, cerebellar cortex, & cerebral cortex.

♣  Excitotoxins: Kainic acid & Pilocarpine

o   Aged rodents are more susceptible to seizure disorders, hypoxia-induced cell damage, and more severe hippocampal degeneration.

o   Female mice tend to have a lower threshold for seizure induction than males

•    FVB/N mice:

o   Used to study seizure: Undergo both excitotoxin induced and spontaneous (audiogenic) seizures which result in neuronal cell death in the hippocampus and cerebral cortex.

o   C57CL/6 are considered excitotoxin, seizure induced cell death resistant and are used as negative controls

o   ‘Space Cadet’ syndrome is a poorly characterized seizure disorder of FVB/N mice more common in middle to older aged female mice.

♣  Clinical Signs: social withdrawal, reduced fertility, aggression, infanticide, and sudden death.

♣  Histo: Neuronal cell death and gliosis in cerebral cortex, hippocampus, and thalamus

♣  Very similar to Status epilepticus or mesial temperal lobe epilepsy

•   GFAP (Glial fibrillary acidic protein) immunohistochemistry

o   GFAP is an intermediate filament found in many cells in the CNS.

o   If gliosis was occurring, there would be an increase in GFAP immunoreactivity.

o   Gliosis: A nonspecific reactive change of glial cells in response to damage to the CNS. Usually hypertrophy of astrocytes, microglia, and oligodendrocytes.

 

Research and Conclusion: This paper looked at histology of CNS of 86 aged FVB/N mice without a history of seizure activity to look for signs of neuronal cell death due to sublethal seizures. No lesions were found and it was concluded that either sublethal seizure activity is rare in FVB/N mice or it fails to lead to histological lesions.

 

QUESTION

1.   Which of the following strains of mice is LEAST susceptible to audiogenic seizures.

a.  DBA/2J

b.  C57BL/6

c. B6.129S1-Adgrvtm1Pwh/J

d.  LP/J

 

ANSWER

1. b

 

Kilic and Kulualp. Efficacy of Several Therapeutic Agents in a Murine Model of Dry Eye Syndrome, pp. 112-118

Primary Species: Mouse (Mus musculus)

 

SUMMARY: Dry Eye Syndrome (DES) is a multifactorial disorder and an important cause of ocular surface disturbances.Tear evaporation rate, hyperosmolarity, and inflammation play key roles in the pathogenesis of DES. Decreases in tear production, cycling, and flow due to low relative humidity, high air flow, and decreased air temperature lead to tear hyperosmolarity, which in turn induces a cascade of inflammatory processes on the ocular surface. 

 

The study population comprised 56 female BALB/c mice. 8 groups of 7 animals were placed in a `dry eye cabinet' with a temperature of 22.5+/-0.4ºC, relative humidity of 25.1%+/-0.6%, air flow rate of 15L/min, and air flow speed of 2.3+/-0.5m/s. Air turbulance was accelerated using air fans (1200+/-250rpm, 50ft3/min).A total of 8 agents were evaluated, and each group of mica received only one agent: Formal saline (FS), Sodium hyaluronate (SH), Olopatadine (OP), Retinoic Acid (RA), Fluoromethalone (FML), Cyclosporine (CsA) and Doxycycline (DS).

 

During the first 2 weeks of the study, all mice were exposed to evaporative stress in the absence of any treatment. then, the right eyes of all animals were instilled with 5uL of the test agent twice daily during weeks 2 to 6 while exposure to evaporative stress continued. All subjects were assessed in terms of blink rate, tear production rate, tear break-up time (TBUT), and impression citology prior to study initiation and at weeks 2, 4 and 6. 

 

After the tests, they conclude that DS and CsA were the most effective therapeutic agents in a mouse model of DES. Both DS and CsA have antinflammatory properties and this characteristic suggests that inflammation plays a key role in the pathogenesis of this particular DES model. 

 

QUESTIONS

1. Which of these opcions is false regarding characteristics of DES?

a. Inflammation

b. Tear film hyposmolarity and instability

c. Vision impairment

d. Multifactorial disorder

2. In which sector of the population is most frequent this disease? And why?

3. Which statement is false:

a. Tear production increases with aging

b. DES is very rare in dogs

c. Treatment is based in alleviating its clinical signs and removing key factors in its development. 

d. DES is occasionally seen in cats and horses 

4. For what are responsible the conjunctival globet cells?

ANSWERS

1. b. Tear film hyperosmolarity)

2. Postmenopausal women, because decreased androgen and estrogen levels.

3. b. Is prevalent in dogs. 

4. Are responsible for the production of the mucin layer.

Nonhuman Primate Models

Todd et al. Vaxar: A Web-Based Database of Laboratory Animal Responses to Vaccinations and Its Application in the Meta-Analysis of Different Animal Responses to Tuberculosis Vaccinations, pp. 119-128

 

SUMMARY: Vaccination is one of the most efficient approaches to protecting humans and animals against infectious and noninfectious diseases. Animal models are indispensable for vaccine research and development. However, choosing which species to use and designing a vaccine study that is optimized for that species is often challenging. Vaxar is a laboratory-animal– oriented tool that supports the curation, organization, and bioinformatic analysis of laboratory animal data in vaccine research and development. This web-based central repository of vaccine animal-response data currently includes manually curated data on 164 pathogens and diseases, 35 animal host species, 3248 vaccines, and 1309 experimental studies of animal responses to these vaccines. Vaxar () is freely available for public query and usage.

 

Mice are the most commonly used laboratory animal model, represented in Vaxar by 848 experiments testing 810 vaccines. Other small laboratory animals used in vaccine studies include guinea pigs, rats, rabbits, hamsters, chickens, ducks, ferrets, and chinchillas. NHP, particularly monkeys (Macaca spp.), are, in most cases, the most important models, due to their phylogenetic proximity to humans.

 

As a case study, the responses of different animal hosts used as animal models for tuberculosis vaccines were considered. In this study, the authors demonstrated how the Vaxar data can be used for meta-analysis to test different hypotheses. The hypothesis driven analysis of the BCG vaccine yielded 8 animal models used in different experimental variable settings in animal-response studies of BCG vaccine. Data from BCG studies recorded in Vaxar revealed that the dosage of BCG administered across species does not relate directly with the species body mass. In addition, the meta-analysis identified 12 vaccine-efficacy assays and showed that the mouse survival assay is the most frequently used assay.

 

Vaxar makes selecting laboratory animal models easier because it uses a unique format to present the responses of laboratory animal models to a particular pathogen or vaccine by using a side-by-side layout to allow for easier comparative analysis of any number of vaccine or pathogen responses. Unlike other vaccine databases, which focus on clinical issues involving commercialized human vaccines, Vaxar includes ongoing research data involving both approved vaccines and vaccine candidates that have been experimentally tested in at least one animal species. This tool allows researchers to compare laboratory species and their responses to specific vaccines side by side to facilitate this process—an advantage that is unavailable in previous databases.

Vaxar is expected to increase understanding of laboratory animal models in vaccine-related studies, thus benefitting the research community, the veterinary and husbandry communities, and the animals themselves. It can be used to facilitate the refinement of animal models for vaccine-related research. For example, the comparison of 8 different BCG vaccine animal models will enable researchers to identify the best animal model for their own BCG research.

In conclusion, these studies indicate that bioinformatics analysis of animal responses to vaccines provides a unique systematic approach toward better understanding of vaccine-induced host responses.

The use of bioinformatics research to allow consideration of the wealth of available literature can potentially refine the selection of animal models, thereby saving researchers time and money and reducing animal use.

 

QUESTIONS

1. What is a weakness of the current Vaxar database?

2. T or F: The animal model that best replicates the human disease for tuberculosis is an ongoing debate among researchers

3. T or F: The Animal Efficacy Rule is also known as the Two-Animal Rule

 

ANSWERS

1. The lack of standard and reproducible representation of vaccine animal response data and knowledge

2. T: because each model has positive and negative considerations in terms of recapitulating the human disease.

3. T: it requires the demonstration of a “reasonably well-understood pathophysiological mechanism” and the use of at least 2 animal species to demonstrate “response predictive for humans”

Bauer and Baker. Persistent Effects of Peer Rearing on Abnormal and Species-Appropriate Activities but Not Social Behavior in Group-Housed Rhesus Macaques (Macaca mulatta), pp. 129-136

 

Domain 1: Management of Spontaneous and Experimentally Induced Diseases and Conditions

T1. Prevent spontaneous or unintended disease or condition; T2. Control spontaneous or unintended disease or condition; T3. Diagnose disease or condition as appropriate; T4. Treat disease or condition as appropriate

Primary Species: Macaques (Macaca spp)

 

SUMMARY: Authors at the Tulane National Primate Research Center closely evaluated the effects of nursery rearing on a large colony of macaques. Nursery rearing is necessary at times because of maternal death or research protocols that require specific pathogen free animals. There are numerous reports of the sequelae of negative behaviors in monkeys such as self-injurious wounding and motor stereotypies [pacing, flipping, circling, or rocking] that are closely correlated with nursery rearing and much effort has been made to reduce the risk of these such behaviors in this population, but this paper looks more closely at subsets of populations to better optimize efforts.

The authors define the subsets of animals as mother-reared, peer-reared, and surrogate-peer-reared. Unexpectedly, no rearing effects on either affiliative or agonistic social behaviors were observed. When peer-reared monkeys were compared with their mother-reared counterparts, they were found to have increased levels of abnormal appetitive, self-directed, and eating behaviors, with lower levels of locomotion and vigilance. Lower foraging behavior was also detected as a trend. Immature peer-reared non-adult monkeys showed more enrichment-directed behavior and drinking with another trend toward inactivity and behaviors associated with anxiety. The study concludes that no new rearing effects were found in adults that had not previously been detected the immature subjects. It is suggested that modern peer-rearing practices may not result in unavoidable abnormal aggressive, rank-related, sexual and emotional behaviors, but once these behaviors surface in monkeys, they may become lifelong abnormal behaviors.

 

QUESTIONS

1.   The ethogram below lists 22 categories of behaviors and definitions that the authors used for data collection. Why would using a similar list of defined behaviors be vital to successfully enriched and managed NHP programs?

2. Are there any behaviors that can be observed in certain at risk monkeys before self-wounding or self-injurious behaviors [SIB] occur?

 

ANSWERS

1.  Consistency of scoring behaviors to categorize facility specific individuals is needed as baseline information [minimum data base] so that any treatment efforts can be interpreted optimally

2.  Self-slap and bizarre postures [other studies have identified ‘floating limb’ as an important precursor of SIB] may be important behaviors to recognize consistently and quickly to prevent SIB.

[pic]

Schlabritz-Loutsevitch et al. Serum Vitamin D Concentrations in Baboons (Papio spp.) during Pregnancy and Obesity, pp. 137-142

Domain 4

Secondary Species: Baboon (Papio spp)

SUMMARY: Vitamin D deficiency during pregnancy is a substantial public health issue associated with maternal and neonatal morbidity. However, the guidelines for vitamin D supplementation during pregnancy have yet to be established. It is known that obesity is associated with vitamin D deficiency; although the definitive reason for this still eludes us, the sequestration of vitamin D in the adipose tissue appears to be an issue. Further, it may also be that obese people have, in general, less sunlight exposure. During pregnancy there is an increased demand for the activities of vitamin D to support the growing fetus.

 

Baboons have been widely used in pregnancy-related research. However, none of the studies in baboons to date have concerned the effect of obesity and pregnancy on vitamin D metabolism. Thus, the current study assessed the effects of obesity, weight loss, and pregnancy on the vitamin D status in baboons. 

 

Data was collected from the following categories of baboons: non-pregnant/obese; non-pregnant/non-obese; non-pregnant after weight reduction; pregnant/obese; pregnant/non-obese; pregnant with sunlight exposure; pregnant without sunlight exposure.

 

As an aside, it should be noted that vitamin D3 is converted into 25-hydroxyvitamin D and the latter is what is typically measured when assessing serum levels of vitamin D. The investigators observed that daily vitamin D3 intake was 71% higher in non-pregnant/obese baboons as compared to their non-pregnant/non-obese counterparts, but serum vitamin D concentrations (measured as 25-hydroxyvitamin D) did not differ between these populations. This suggests that the obesity condition results in a need to consume much larger amounts of vitamin D3 in order to maintain normal serum levels and thus the vitamin D3 supplementation levels for such animals may need to be increased 2-3 fold as compared to non-obese counterparts. It was also observed that weight reduction in the non-pregnant/obese baboons did not result in a significant difference in serum vitamin D concentrations.

 

Regarding obese baboons, plasma concentrations of vitamin D3 did not significantly differ between sunlight-exposed (exposed to direct sunlight) as compared to non-sunlight-exposed (not exposed to direct sunlight) pregnant baboons or their fetuses. The authors hypothesized that this may be because the placenta is producing vitamin D3 or that the lower levels of sunlight exposure were still sufficient to produce the needed vitamin D3 in the baboons.    

 

However, it was found that the serum concentrations of 25-hydroxyvitamin D were higher in pregnant/non-obese baboons as compared to pregnant/obese baboons. This report is the first to show the effect of obesity and pregnancy on vitamin D concentrations in a NHP species and thus underscores the importance of adequate vitamin D supplementation in obese animals. 

        

QUESTIONS (True or False)

1. Very few foods contain vitamin D (e.g. without vitamin supplementation) making exposure to sunlight the main source of vitamin D for most species?

2. NWMs are deficient in their ability to make vitamin D3 from sunlight?

3. In this study, the serum 25-hydroxyvitamin D concentrations correlated positively with the pregnant/obese condition?

ANSWERS:

1.  True

2.  True

3. False, correlated negatively

Bauer and Harrison. Retrospective Analysis of the Incidence of Retained Placenta in 3 Large Colonies of NHP, pp. 143-149

Domain 1:

Primary Species: Macaques (Macaca spp)

Secondary Species: Baboons (Papio spp)

 

SUMMARY: During 1999 through 2014, retained placenta was the most common cause of clinical admission for reproductive complications in breeding colonies of baboons (approximate colony size, 2000 animals), cynomolgus macaques (approximately 1000), and rhesus macaques (approximately 500) at the Southwest National Primate Research Center.

Retained placentas occurred in 2.7% of baboons, 3.3% of cynomolgus macaques, and 1.0% of rhesus macaques. Apparent risk factors for retained placenta included stillbirth or abortion and at least one prior cesarean section. Having had at least one prior cesarean section was an incidence factor for retained placenta in 37.0% of baboons and 4.7% of cynomolgus macaques; none of the rhesus macaques with retained placentas had undergone cesarean section previously. More than 90% of dams with retained placenta returned to a successful reproductive life or assignment to a nonbreeding research protocol.

Prior cesarean section and premature delivery are among the known risk factors for retained placenta in humans, and these associations are similar to the findings of the current study, most notably for baboons. Many baboons had undergone at least 1 prior cesarean section due to previous research demands, and the incidence of retained placenta in animals with a prior cesarean section was high in this colony (36.1%). In contrast, few cesarean sections were performed in either of the macaque colonies, and the incidence of subsequent retained placentas was relatively low as well (4.7% in cynomolgus macaques and 0% in rhesus macaques). Premature delivery likely causes an abnormal cascade in the hormonal and mechanical events that initiate parturition, thus leading to the retention of the placenta, and premature delivery showed likely association with retained placenta in baboons (9.5%); the incidence of premature delivery was not determined for cynomolgus and rhesus macaques.

In a few NHP, parturition was induced after a traumatic event inflicted by conspecific cage-mates. Twinning is uncommon in baboons and cynomolgus and rhesus macaques, but when it occurred in conjunction with retained placenta, both placentas were retained. After resolution of the retained placenta, followed by a recovery period of reproductive rest, many NHP were able to return to breeding. After experiencing and recovering from retained placenta, some NHP were able to give birth with no complications, others again retained the placenta, and still others never became pregnant again despite being housed with a fertile male.

Advances in the reproductive management of NHP will benefit from comparisons driven by data collection strategies oriented to all members of a reproductive breeding group prior to reproductive complications. Data meriting universal collection are gestational diabetic status, the presence of tears to the vagina, bacterial infection, gestational day at birth, parity, birth weight, and body condition score of the dams. Overall, the range of contributing physiologic differences across primate species warrants further examination

  

QUESTIONS

1. When twinning occurs in conjunction with a retained placenta, which placenta is retained?

a. Left

b. Right

c. No preference for either side

d. Both

2. Having had at least one prior cesarean section was an incidence factor for retained placenta in what percentage of baboons?

a. 74%

b. 37%

c. 11%

d. 3%

 

ANSWERS

1. d

2. b

Gulani et al. Cercopithecine Herpesvirus 9 (Simian Varicella Virus) Infection after Total-Body Irradiation in a Rhesus Macaque (Macaca mulatta), pp. 150-153

Domain 1: Management of Spontaneous and Experimentally Induced Diseases and Conditions

Primary Species: Macaques (Macaca spp)

One-Line Summary: This report describes a male 5-y old rhesus macaque that was diagnosed posthumously to be infected with Cercopithecine herpesvirus 9 (Simian Varicella Virus) 30 days after total body irradiation showing generalized skin rashes and non-specific clinical signs.

 

SUMMARY: A male 5yr old rhesus macaque showed generalized skin rashes and non-specific clinical signs such as anorexia, dehydration, lethargy and ataxia, 30 days after total body irradiation at 6.5Gy.   Physical examination showed pale mucous membranes, a capillary refill time of 4s, heart rate of 180bpm and respirations at 50 breaths/min.  Of note were the severe diffuse multifocal maculopapulovesicular rashes that were present on the body and mucocutaneous junctions along the animal’s body.  The animal was euthanized and a postmortem done.  On gross examination pathologic lesions were found on the liver and surface of the GIT, in the lymph nodes and thoracic cavity.  The predominant microscopic lesion was intranuclear eosinophilic viral inclusions within epithelial cells consistent with herpesvirus infections.  The presence of Simian Varicella Virus (SVV) were then confirmed via PCR analysis, immunohistochemistry and histology.

 

QUESTIONS

1.  What are the adverse effects of total body irradiation (TBI)?

2.   List the Clinical Components of Acute Radiation Syndrome.

3.  Which group of white blood cells are particularly sensitive to radiation injury?

4.  Which two groups of blood cells are lost or reduced from circulation after exposure to radiation and in what order of disappearance?

 

ANSWERS

1.  Total Body Irradiation causes suppression of the bone marrow which leads to marked reduction in the RBC, platelet and WBC counts. It can cause skin lesions, such as petechiation, due to thrombocytopenia.

2. The hematopoietic, gastrointestinal and cerebrovascular subsyndromes.

3.  The lymphocytes

4.  Lymphocyte loss is followed by neutrophil loss or reduction and then platelet loss or reduction after exposure to radiation.

Beck et al. Malignant Neoplasia of the Sex Skin in 2 Chimpanzees (Pan troglodytes), pp. 154-161

 

Domain 1: Management of Spontaneous and Experimentally Induced Diseases and Conditions

Tertiary Species: Other Nonhuman Primates

 

SUMMARY: In the first case, a fifty year old female chimpanzee presented in November 2014 for a persistent nonhealing wound to her sex skin.  The wound had been treated for several months with a variety of treatments without resolution.  On the presentation in November, two biopsies were collected and submitted for histopathology.  The histology of the mass was consistent with squamous cell carcinoma.  Since the chimpanzee was in good body condition and appeared comfortable, she was placed on a monitoring program including a quality-of-life watch.   

In the second case, a forty eight year old female chimpanzee presented in October 2014 for a nonhealing wound to her sex skin.  Two punch biopsies and wedge biopsies of the lesion were taken and examined histologically.  The preliminary diagnosis was a metastatic malignant neoplasm.  Additional diagnostics determined the mass was most likely a metastatic adenocarcinoma, potentially derived from the apocrine glands.  Soon after diagnosis, the chimpanzee appeared to have more discomfort with cleaning of the wound.  A recheck exam would show that the tumor had increased in size.  Given the poor prognosis, the chimpanzee was euthanized within 2 months of initial presentation.

 

QUESTIONS

1. What is the average or expected lifespan of Pan troglodytes?

2. T/F.  Development of neoplasia in chimpanzees is an uncommon occurrence.

3. Name three reasons why surgical resection of tumors is especially difficult in chimpanzees.

 

ANSWERS

1. Average lifespan in the wild is approximately 45 years.  Average lifespan in captivity is approximately 30 years; however, the oldest known chimpanzee in captivity was approximately 60 years old.

2. True. However, as the population of captive chimpanzees ages, it is expected that it will become more common. 

3. *They often attempt to remove sutures postoperatively

*They may contaminate postoperative areas with fecal material

*Social conspecifics maygroom postoperative area and cause trauma, thereby necessitating individual housing which is undesirable in a social species. 

 

Reader et al. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992-2014), pp. 162-169

Primary Species: Macaque (Macaca spp.)

 

SUMMARY: In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy (LVH).  Outcomes of HCM in humans can range from asymptomatic disease to sudden death.  The overall risk of severe complications from HCM in human (sudden death, heart failure and stroke) is low, however absolute risk can be very high or very low, which can impact individuals significantly. Macaques also develop idiopathic LVH.  To better understand if spontaneously occurring cases of LVH in macaques could serve as a model for human HCM, clinical histories and necropsy records from animals in the rhesus macaque colony at the CNPRC were reviewed to identify cases where mortality was associated with LVH.  

 

Twenty-one years of macaque records were reviewed, and 162 cases of idiopathic LVH (90 female, 72 male) were identified.  Necropsy findings included prominent concentric hypertrophy of the left ventricle and a severe reduction of the ventricular lumen. Histologic changes were subtle and included karyomegaly of the cardiac cells, and increased cardiac myocyte diameter.  74/162 cases presented to necropsy as sudden deaths. Most of these were young adults.  More than half of the cases of sudden death had a recent history of sedation or intraspecific aggression. This study demonstrates that spontaneous LVH in macaques may serve as a useful model of human HCM and allow a better understanding of the pathogenesis of this disease.

 

QUESTIONS (True or False)

1.  Sudden death from LVH in macaques can be associated with recent sedation events.

2.  LVH in macaques is different from HCM in humans, because LVH in macaques is rarely idiopathic and most often associated with viral causes.

 

ANSWERS

1.  True

2.  False

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