Spontaneous intestinal adenocarcinoma in geriatric macaques (Macaca sp.).

BACKGROUND AND PURPOSE: Intestinal adenocarcinoma appears to be the most common malignant neoplasm in macaques, and is a substantial cause of morbidity and mortality in the elderly. METHODS: A retrospective review of 32 cases was done. RESULTS: Thirty-two cases were reviewed. Clinical examination had revealed severe weight loss, anorexia, and palpable abdominal mass. Microcytic hypochromic anemia, intermittent fecal occult blood positive test results, hypoproteinemia, and hypoalbuminemia were the predominant clinical laboratory findings. Carcinoembryogenic antigen serologic testing and single-strand conformational polymorphism analysis were performed in selected cases. The most common sites of the intestinal adenocarcinoma were ileocecal junction, colon, ileum, jejunum, and cecum. Metastases were evident in 34% of the cases and involved peripheral nodes, liver, lungs, pancreas, and adrenal gland. Overall survival of 12 macaques that underwent surgical excision was 83% at 6 months, 58% at 1 year, 50% at 1.5 years, 33% at 2 years, and 8% at 4 years. The overall mean survival rate (MSR) was > 483 postoperative days. CONCLUSION: Intestinal adenocarcinomas should be amenable to surgical resection. Early detection of localized, non-invasive neoplasms will increase surgical cure rate. Survivability could be potentially improved by use of adjuvant therapies.

Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys (Macaca mulatta).

OBJECTIVE: To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys. ANIMALS: 6 adult male rhesus monkeys. PROCEDURE: Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory. RESULTS: Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, Paco2, and Pao2 ranged from 7.46 +/- 0.04 to 751 +/- 0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/- 105.3 to 482.9 +/- 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 70 +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 + 0.001/min, and 192.0 +/- 33.5 min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans.

T-cell lymphoproliferative disorder in an aged rhesus macaque.

A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although leukemia and lymphoma in nonhuman primates are commonly associated with simian T-lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types C, D, and E retroviruses, this monkey was not infected with any of these viruses. However, the monkey did have antibodies against herpesvirus saimiri. This likely represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that were identified as having antibodies against herpesvirus saimiri. Rhesus rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to lymphoproliferative disorders in primates and humans, respectively. Moreover, an oncogene has been recently identified in the RRV genome that is equivalent in position to the herpesvirus saimiri and KSHV oncogenes. Presently, the association of RRV infection with disease in nonhuman primates is unknown.

Renal transplantation in cats.

Feline renal transplantation can offer long-term survival with a normal quality of life for cats with renal failure. However, it is important to remember that renal transplantation is a treatment option and not a cure. Renal transplantation is never performed on an emergency basis or prophylactically. Feline renal transplantation requires special microvascular instruments and an operating microscope. Careful patient selection and perioperative monitoring have improved the success rate. The new microemulsified form of cyclosporine is recommended for immunosuppression. As survival times have steadily improved, long-term complications, such as diabetes and neoplasia, are now being recognized.

Cardiovascular, respiratory, thermoregulatory, sedative, and analgesic effects of intravenous administration of medetomidine in rhesus macaques (Macaca mulatta).

BACKGROUND AND PURPOSE: Medetomidine is a selective, specific, and potent alpha2-adrenergic receptor agonist that has been utilized successfully as a sedative/analgesic agent in a variety of domestic and nondomestic animals. The objective of this study was to document the physiological effects of the intravenous administration of medetomidine in rhesus macaques (Macaca mulatta). METHODS: Fifteen healthy rhesus macaques (Macaca mulatta), 5 to 15 years old and weighing 5.5 to 11.8 kg, were given four dosages of medetomidine (50, 100, 150, and 200 microg/kg of body weight) intravenously, and cardiovascular, respiratory, thermoregulatory, sedative, and analgesic effects were determined. RESULTS: All four doses of medetomidine induced a similar and significant decrease in mean arterial pressure, as well as a transient but significant increase in respiratory rate followed by a longer-lasting significant decrease. Bradycardia, hypotension, and loss of thermoregulatory ability accompanied by a biphasic respiratory response and inconsistent sedation, analgesia, and muscular relaxation were observed. Heart rate decrease was rapid for all doses, but was significantly lower and of shorter duration after administration of the 50 microg/kg dosage. CONCLUSION: The inconsistency of the anesthetic plane induced by intravenous administration of medetomidine precludes it from being used alone to sedate rhesus macaques.

Spontaneous leprosy in a wild-caught cynomolgus macaque.

Naturally occurring Mycobacterium leprae has been previously documented in only two species of nonhuman primates from West Africa--the chimpanzee and the sooty mangabey. We report here the first known case of spontaneous leprosy in an Asian macaque. A wild-caught cynomolgus macaque imported from The Philippines developed a reaction to a tuberculin skin test after 3 years at the California Regional Primate Research Center (CRPRC), University of California-Davis, Davis, California, U.S.A. Biopsies of concurrent skin lesions suggested a cutaneous mycobacterial infection. Diagnosis of the infection was obtained by a polymerase chain reaction (PCR) assay specific for M. leprae. Clinical presentation, histopathological findings, and ELISA serology for M. leprae-specific PGL-I and to the LAM mycobacterial antigens were consistent with those of human borderline (BB) leprosy. Longitudinal serologic data suggest that the cynomolgus macaque had subclinical leprosy at the time of arrival in the CRPRC quarantine. Intradermal tuberculin testing is the traditional method for screening nonhuman primate populations for mycobacterial infections. Exposure to nontuberculous mycobacteria, such as M. leprae, amy sensitize some individual primates to nonspecific mycobacterial antigens, resulting in false-positive tuberculin reactions. Susceptibility of the cynomolgus macaque and other nonhuman primates to M. leprae should be re-evaluated. Cynomolgus macaques and, possibly, other nonhuman primates may serve as valuable experimental models of leprosy in humans.

Characterization of the onset of menopause in the rhesus macaque.

The objective of this study was to assess ovarian activity in a cohort of aged female rhesus macaques. Menstrual records for 26 rhesus macaques ages 20-29 yr were evaluated over a 1-yr period, and daily urinary estrone conjugate (E1C) and pregnanediol-3-glucuronide (Hygeia [Hy]-PdG) levels were determined for 12 wk. Each animal was categorized as either pre-, peri-, or postmenopausal based on menstrual and hormonal data. Eleven animals (mean age 22.5 yr) were premenopausal, thirteen (mean age 24 yr) were perimenopausal, and two (mean age 29.5 yr) were postmenopausal. Hormone profiles for perimenopausal animals reveal prolonged follicular phases and/or a lack of patterned Hy-PdG dynamics. Breakthrough bleeding occurred in four of these perimenopausal animals. The postmenopausal animals were amenorrheic and exhibited low E1C levels (less than 10 ng/mg creatinine). The results of this study illustrate that the decline of ovarian function in female macaques during the third decade of life parallels the menstrual and hormonal events associated with the climacteric in women, and that menopause does occur in rhesus macaques.

Spontaneous rat bite fever in non-human primates: a review of two cases.

Rat bite fever is a worldwide zoonotic, non-reportable disease. This entity encompasses similar, yet distinct, disease syndromes caused by Streptobacillus moniliformis or Spirillum minus. Naturally occurring rat bite fever has not been previously described in non-human primates. This report describes two cases of non-human primate rat bite fever caused by S. moniliformis; a rhesus macaque (Macaca mullata) with valvular endocarditis, and a titi monkey (Callicebus sp.) with septic arthritis. Potential sources of infection included direct contact, and ingestion of surface water or feed contaminated with rodent feces.

Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration.

Access of recombinant proteins to the retina following intravitreal administration is poorly understood. A study was conducted in male Rhesus monkeys (15 to 28 mo of age; 2.8-3.3 kg) in order to compare the intraocular tissue distribution, pharmacokinetics, and safety of 125Iodine (I)-labeled full-length humanized rhuMAb HER2 antibody (148 kD) and of 125I-labeled humanized rhuMAb vascular endothelial growth factor Fab antibody (48.3 kD) following bilateral bolus intravitreal injection on day 0 (5 animals/group). The dose administered to each eye was 25 microg (9-10 microCi) in 50 microl. Animals were euthanatized on day 0 (1 hr postdose) and on days 1, 4, 7, and 14. Safety assessment included direct ophthalmoscopy, intraocular pressure measurements, clinical observations, body weight, and hematology and clinical chemistry panels. Blood and vitreous samples were collected daily (blood only) and at necropsy for pharmacokinetics and analysis for antibodies to the test materials; the ocular tissue distribution of the test material was evaluated by microautoradiography. All animals completed the study. Microautoradiography demonstrated that the full-length antibody did not penetrate the inner limiting membrane of the retina at any of the time points examined. In contrast, the Fab antibody fragment diffused through the neural retina to the retinal pigment epithelial layer at the 1-hr time point and persisted in this location for up to 7 days. Systemic exposure to test material was low but variable: the highest plasma concentration of the full-length antibody was 20.3 ng/ml, whereas plasma concentrations for the Fab antibody remained below the limit of quantitation (i.e., <7.8 ng/ml). An immune response to the test material was not evident in either treatment group. The half-life in vitreous was 5.6 days for the full-length antibody and 3.2 days for the Fab antibody. The shorter intravitreal half-life of the Fab antibody is related to its smaller size and its significant diffusion through the retinal layers. The differences in pharmacokinetics and tissue distribution that are noted between the full-length and Fab antibodies in this study identify potential therapeutic approaches that may be exploited in specific disease conditions.

Passive immunization of newborn rhesus macaques prevents oral simian immunodeficiency virus infection.

To determine if passively acquired antiviral antibodies modulate virus transmission and disease progression in human pediatric AIDS, the potential of pre- and postexposure passive immunization with hyperimmune serum to prevent oral simian immunodeficiency virus (SIV) infection or disease progression in newborn rhesus macaques was tested. Untreated neonates became infected after oral SIV inoculation and had high viremia, and most animals developed fatal AIDS within 3 months. In contrast, SIV hyperimmune serum given subcutaneously prior to oral SIV inoculation protected 6 newborns against infection. When this SIV hyperimmune serum was given to 3 newborns 3 weeks after oral SIV inoculation, viremia was not reduced, and all 3 infants died within 3 months of age due to AIDS and immune-complex disease. These results suggest that passively acquired antihuman immunodeficiency virus (HIV) IgG may decrease perinatal HIV transmission. However, anti-HIV IgG may not impart therapeutic benefit to infants with established HIV infection.