Helicobacter suis and Helicobacter pylori infection in a colony of research macaques: characterization and clinical correlates.

Introduction. Helicobacter suis (Helicobacter heilmannii type 1) commonly infects nonhuman primates but its clinical importance is in question.Aim. To characterize H. suis infection in a colony of rhesus macaques (Macaca mulatta) used in cognitive neuroscience research.Hypothesis/Gap Statement. Inquiries into the nature of Helicobacter suis in nonhuman primates are required to further define the organism's virulence and the experimental animal's gastric microbiome.Methodology. Animals with and without clinical signs of vomiting and abdominal pain (n=5 and n=16, respectively) were evaluated by histology, culture, PCR amplification and sequencing, fluorescent in situ hybridization (FISH) and serology. Three of the five animals with clinical signs, an index case and two others, were evaluated before and after antimicrobial therapy.Results. The index animal had endoscopically visible ulcers and multifocal, moderate, chronic lymphoplasmacytic gastritis with intraglandular and luminal spiral bacteria. Antimicrobial therapy in the index animal achieved histologic improvement, elimination of endoscopically visible ulcers, and evident eradication but clinical signs persisted. In the other treated animals, gastritis scores were not consistently altered, gastric bacteria persisted, but vomiting and abdominal discomfort abated.Nineteen of 21 animals were PCR positive for H. suis and five animals were also PCR positive for H. pylori. Organisms were detected by FISH in 17 of 21 animals: 16S rRNA sequences of two of these were shown to be H. suis. Mild to moderate lymphoplasmacytic gastritis was seen in antrum, body and cardia, with antral gastritis more likely to be moderate than that of the body.Conclusion. No clear association between the bacterial numbers of Helicobacter spp. and the degree of inflammation was observed. H. suis is prevalent in this colony of Macaca mulatta but its clinical importance remains unclear. This study corroborates many of the findings in earlier studies of H. suis infection in macaques but also identifies at least one animal in which gastritis and endoscopically visible gastric ulcers were strongly associated with H. suis infection. In this study, serology was an inadequate biomarker for endoscopic evaluation in diagnosis of H. suis infection.

Accuracy of cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm to identify sites of origin of cardiac electrical activation.

We have developed a system that could potentially be used to identify the site of origin of ventricular tachycardia (VT) and to guide a catheter to that site to deliver radio-frequency ablation therapy. This system employs the Inverse Solution Guidance Algorithm based upon Single Equivalent Moving Dipole (SEMD) localization method. The system was evaluated in in vivo swine experiments. Arrays consisting of 9 or 16 bipolar epicardial electrodes and an additional mid-myocardial pacing lead were sutured to each ventricle. Focal tachycardia was simulated by applying pacing pulses to each epicardial electrode at multiple pacing rates during breath hold at the end-expiration phase. Surface potentials were recorded from 64 surface electrodes and then analyzed using the SEMD method to localize the position of the pacing electrodes. We found a close correlation between the locations of the pacing electrodes as measured in computational and real spaces. The reproducibility error of the SEMD estimation of electrode location was 0.21 ± 0.07 cm. The vectors between every pair of bipolar electrodes were computed in computational and real spaces. At 120 bpm, the lengths of the vectors in the computational and real space had a 95% correlation. Computational space vectors were used in catheter guidance simulations which showed that this method could reduce the distance between the real space locations of the emulated catheter tip and the emulated arrhythmia origin site by approximately 72% with each movement. We have demonstrated the feasibility of using our system to guide a catheter to the site of the emulated VT origin.

Nanoscale Bupivacaine Formulations To Enhance the Duration and Safety of Intravenous Regional Anesthesia.

Intravenous regional anesthesia (IVRA; Bier block) is commonly used to anesthetize an extremity for surgery. Limitations of the procedure include pain from the required tourniquet, the toxicity that can occur from systemic release of local anesthetics, and the lack of postoperative pain relief. We hypothesized that the nanoencapsulation of the local anesthetic would prolong local anesthesia and enhance safety. Here, we developed an ∼15 nm micellar bupivacaine formulation (M-Bup) and tested it in a rat tail vein IVRA model, in which active agents were restricted in the tail by a tourniquet for 15 min. After tourniquet removal, M-Bup provided local anesthesia for 4.5 h, which was two times longer than that from a larger dose of free bupivacaine. Approximately 100 nm liposomal bupivacaine (L-Bup) with the same drug dose as M-Bup did not cause anesthesia. Blood levels of bupivacaine after tourniquet removal were lower in animals receiving M-Bup than L-Bup or free bupivacaine, demonstrating enhanced safety. Tissue reaction to M-Bup was benign.

Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques.

Non-human primates (NHPs) for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants isolation and antibiotic testing of enteric pathogens before treating macaques with quinolones prophylactically or therapeutically.

Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques.

BACKGROUND: Many Escherichia coli strains are considered to be a component of the normal flora found in the human and animal intestinal tracts. While most E. coli strains are commensal, some strains encode virulence factors that enable the bacteria to cause intestinal and extra-intestinal clinically-relevant infections. Colibactin, encoded by a genomic island (pks island), and cytotoxic necrotizing factor (CNF), encoded by the cnf gene, are genotoxic and can modulate cellular differentiation, apoptosis and proliferation. Some commensal and pathogenic pks+ and cnf+ E. coli strains have been associated with inflammation and cancer in humans and animals. RESULTS: In the present study, E. coli strains encoding colibactin and CNF were identified in macaque samples. We performed bacterial cultures utilizing rectal swabs and extra-intestinal samples from clinically normal macaques. A total of 239 E. coli strains were isolated from 266 macaques. The strains were identified biochemically and selected isolates were serotyped as O88:H4, O25:H4, O7:H7, OM:H14, and OM:H16. Specific PCR for pks and cnf1 gene amplification, and phylogenetic group identification were performed on all E. coli strains. Among the 239 isolates, 41 (17.2%) were pks+/cnf1-, 19 (7.9%) were pks-/cnf1+, and 31 (13.0%) were pks+/cnf1+. One hundred forty-eight (61.9%) E. coli isolates were negative for both genes (pks-/cnf1-). In total, 72 (30.1%) were positive for pks genes, and 50 (20.9%) were positive for cnf1. No cnf2+ isolates were detected. Both pks+ and cnf1+ E. coli strains belonged mainly to phylogenetic group B2, including B21. Colibactin and CNF cytotoxic activities were observed using a HeLa cell cytotoxicity assay in representative isolates. Whole genome sequencing of 10 representative E. coli strains confirmed the presence of virulence factors and antibiotic resistance genes in rhesus macaque E. coli isolates. CONCLUSIONS: Our findings indicate that colibactin- and CNF-encoding E. coli colonize laboratory macaques and can potentially cause clinical and subclinical diseases that impact macaque models.

Adult-onset, chronic, cyclic thrombocytopenia in a Rhesus macaque (Macaca mulatta) after dengue virus vaccination and viral challenge.

An 8-year-old, male Rhesus macaque (Macaca mulatta), previously used for dengue virus (DENV) vaccine research with viral challenge, was presented with adult-onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and function were evaluated by automated hematology, peripheral blood smears, electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was evaluated by cytology. Both serum anti-dengue nonstructural protein 1 (NS1) antibodies and anti-platelet antibodies were detected by ELISA. Platelet characterization showed a lack of aggregation to all agonists (ADP, ASP, and collagen), increased activation with increased expression of surface marker (HLA-ABC), and an absence of surface receptor GPIX during clinical episodes of petechiae and ecchymoses, even in the presence of normal platelet counts. Bone marrow aspirates identified potential mild megakaryocytic hypoplasia. All platelet functions and morphologic attributes were within normal limits during clinically normal phases. Presence of anti-dengue NS1 serum antibodies confirmed a positive DENV titer 8 years postvaccination. Based on the history and clinical findings, a primary differential diagnosis for this chronic, cyclic platelet pathology was autoimmune platelet destruction with potential bone marrow involvement.

Local and Systemic Changes Associated with Long-term, Percutaneous, Static Implantation of Titanium Alloys in Rhesus Macaques (Macaca mulatta).

Metal alloys are frequently used as implant materials in veterinary medicine. Recent studies suggest that many alloys induce both local and systemic inflammatory responses. In this study, 37 rhesus macaques with long-term skull-anchored percutaneous titanium alloy implants (duration, 0 to 14 y) were evaluated for changes in their hematology, coagulation, and serum chemistry profiles. Negative controls (n = 28) did not have implants. Macaques with implants had higher plasma D-dimer and lower antithrombin III concentrations than nonimplanted animals. In addition, animals with implants had higher globulin and lower albumin and calcium concentrations compared with nonimplanted macaques. Many of these changes were positively correlated with duration of implantation and the number of implants. Chronic bacterial infection of the skin was present around many of the implant sites and within deeper tissues. Representative histopathology around the implant site of 2 macaques revealed chronic suppurative to pyogranulomatous inflammation extending from the skin to the dura mater. X-ray fluorescence microscopy of tissue biopsies from the implant site of the same 2 animals revealed significantly higher levels of free metal ions in the tissue, including titanium and iron. The higher levels of free metal ions persisted in the tissues for as long as 6 mo after explantation. These results suggest that long-term skull-anchored percutaneous titanium alloy implants can be associated with localized inflammation, chronic infection, and leaching of metal ions into local tissues.

Coagulation Biomarkers in Healthy Chinese-Origin Rhesus Macaques (Macaca mulatta).

Rhesus macaques (Macaca mulatta) are a common model for the study of human biology and disease. To manage coagulopathies in these animals and to study their clotting changes, the ability to measure coagulation biomarkers is necessary. Currently, few options for coagulation testing in NHP are commercially available. In this study, assays for 4 coagulation biomarkers-D-dimer, antithrombin III, protein C, and soluble P-selectin-were developed and optimized for rhesus macaques. Whole blood was collected from 28 healthy Chinese-origin rhesus macaques (11 male; 17 female) ranging in age from 5 to 20 y. Coagulation biomarkers were measured by using bead-based sandwich ELISA technology. The ranges (mean ± 90% confidence interval) for these biomarkers were: antithrombin III, 124.2 to 133.4 µg/mL; protein C, 3.2 to 3.6 µg/mL; D-dimer, 110.3 to 161.3 ng/mL; soluble P-selectin, 0.12 to 0.14 ng/10(6) platelets. These reference values did not differ significantly according to sex or age. These new assays for coagulation biomarkers in rhesus macaques will facilitate the evaluation of in vivo hemostasis.

Spontaneous Cholelithiasis in a Squirrel Monkey (Saimiri sciureus).

A mature female squirrel monkey was noted during routine semiannual examinations to have moderate progressive weight loss. Serum chemistry panels revealed marked increases in hepatic enzyme, bilirubin, and bile salt concentrations and hypoalbuminemia. Abdominal ultrasonography revealed echogenic, shadowing debris in the gallbladder, consistent with cholelithiasis. At necropsy, marked thickening and distension of the gallbladder, cystic duct, and common bile duct was noted, and more than 50 irregularly shaped, black gallstones were removed from the biliary tract. Gallbladder tissue, bile, and gallstones cultured positive for Escherichia coli and Proteus spp., suggesting a brown-pigment gallstone type secondary to a bacterial nidus. Histopathology revealed severe chronic-active diffuse cholecystitis and severe chronic-active hepatic degeneration and necrosis with severe cholestasis. To our knowledge, this report is the first description of spontaneous choleilthiasis in a squirrel monkey.

Noninvasive temporal artery thermometry as an alternative to rectal thermometry in research macaques ( Macaca spp.).

Obtaining an animal's body temperature is essential for the assessment of its clinical status. For many species, rectal thermometry is the technique used most often; however, this method in macaques typically requires sedation or considerable physical restraint. A noninvasive and inexpensive temporal artery (TA) thermometer was evaluated as an alternative method for collecting body temperature measurements from macaques used in neuroscience research. Rectal and arterial temperatures were obtained from 86 macaques (mean age, 10.2 y) that had received ketamine (10 mg/kg IM) or Telazol (5 mg/kg IM); the arterial measurements were taken from behind the right ear. In addition, arterial temperatures were measured behind both ears in a cohort of awake, chaired macaques with cephalic restraint pedestals only (n = 8) or with cephalic restraint pedestals and recording chambers (n = 14). Within-subject repeatability for TA thermometry and agreement between rectal and arterial temperature measurements were assessed by using the Bland-Altman method. Temperature measurements indicated that values from TA thermometry were lower than those from rectal thermometry by 1.57 °C with a 95% agreement limit of ± 1.27 °C. Results show satisfactory repeatability with TA thermometry and agreement between arterial and rectal temperatures, demonstrating that TA thermometry can be a valuable tool in conscious, chaired macaques with restrained heads.

Cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm.

BACKGROUND: We developed and evaluated a novel system for guiding radiofrequency catheter ablation therapy of ventricular tachycardia. This guidance system employs an inverse solution guidance algorithm (ISGA) using a single equivalent moving dipole (SEMD) localization method. The method and system were evaluated in both a saline tank phantom model and in vivo animal (swine) experiments. METHODS: A catheter with two platinum electrodes spaced 3 mm apart was used as the dipole source in the phantom study. A 40-Hz sinusoidal signal was applied to the electrode pair. In the animal study, four to eight electrodes were sutured onto the right ventricle. These electrodes were connected to a stimulus generator delivering 1-ms duration pacing pulses. Signals were recorded from 64 electrodes, located either on the inner surface of the saline tank or on the body surface of the pig, and then processed by the ISGA to localize the physical or bioelectrical SEMD. RESULTS: In the phantom studies, the guidance algorithm was used to advance a catheter tip to the location of the source dipole. The distance from the final position of the catheter tip to the position of the target dipole was 2.22 ± 0.78 mm in real space and 1.38 ± 0.78 mm in image space (computational space). The ISGA successfully tracked the locations of electrodes sutured on the ventricular myocardium and the movement of an endocardial catheter placed in the animal's right ventricle. CONCLUSION: In conclusion, we successfully demonstrated the feasibility of using an SEMD inverse algorithm to guide a cardiac ablation catheter.

Characterization of Corynebacterium species in macaques.

Bacteria of the genus Corynebacterium are important primary and opportunistic pathogens. Many are zoonotic agents. In this report, phenotypic (API Coryne analysis), genetic (rpoB and 16S rRNA gene sequencing), and physical methods (MS) were used to distinguish the closely related diphtheroid species Corynebacterium ulcerans and Corynebacterium pseudotuberculosis, and to definitively diagnose Corynebacterium renale from cephalic implants of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques used in cognitive neuroscience research. Throat and cephalic implant cultures yielded 85 isolates from 43 macaques. Identification by API Coryne yielded C. ulcerans (n = 74), Corynebacterium pseudotuberculosis (n = 2), C. renale or most closely related to C. renale (n = 3), and commensals and opportunists (n = 6). The two isolates identified as C. pseudotuberculosis by API Coryne required genetic and MS analysis for accurate characterization as C. ulcerans. Of three isolates identified as C. renale by 16S rRNA gene sequencing, only one could be confirmed as such by API Coryne, rpoB gene sequencing and MS. This study emphasizes the importance of adjunct methods in identification of coryneforms and is the first isolation of C. renale from cephalic implants in macaques.

Chronic anemia and effects of iron supplementation in a research colony of adult Rhesus macaques (Macaca mulatta).

A cohort of rhesus macaques used in neuroscience research was found at routine examinations to have chronic anemia (spun Hct less than 30%). Four anemic (Hct, 24.8% ± 3.4%) and 10 control (39.6% ± 2.9%) macaques were assessed to characterize the anemia and determine probable cause(s); some animals in both groups had cephalic implants. Diagnostic tests included CBC, bone marrow evaluations, iron panels, and serum erythropoietin and hepcidin concentrations. Serum iron and ferritin were 15.8 ± 11.1 µg/dL and 103.8 ± 53.1 ng/mL, respectively, for the anemic group compared with 109.8 ± 23.8 µL/dL and 88.5 ± 41.9 ng/mL, respectively, for the control group. Erythropoietin levels were 16.2 to over 100 mU/mL for the anemic macaques compared with 0 to 1.3 mU/mL for the control group. Hepcidin results were similar in both groups. Because the findings of low iron, high erythropoietin, and normal hepcidin in the anemic macaques supported iron-deficiency anemia or anemia of chronic disease combined with iron-deficiency anemia, a regimen of 4 doses of iron dextran was provided. In treated macaques, Hct rose to 36.3% ± 6.8%, serum iron levels increased to 94.0 ± 41.9 µg/dL, and erythropoietin levels fell to 0.15 to 0.55 mU/mL. Maintenance of normal Hct was variable between macaques and reflected individual ongoing clinical events.

Estimation of changes in instantaneous aortic blood flow by the analysis of arterial blood pressure.

The purpose of this study was to introduce and validate a new algorithm to estimate instantaneous aortic blood flow (ABF) by mathematical analysis of arterial blood pressure (ABP) waveforms. The algorithm is based on an autoregressive with exogenous input (ARX) model. We applied this algorithm to diastolic ABP waveforms to estimate the autoregressive model coefficients by requiring the estimated diastolic flow to be zero. The algorithm incorporating the coefficients was then applied to the entire ABP signal to estimate ABF. The algorithm was applied to six Yorkshire swine data sets over a wide range of physiological conditions for validation. Quantitative measures of waveform shape (standard deviation, skewness, and kurtosis), as well as stroke volume and cardiac output from the estimated ABF, were computed. Values of these measures were compared with those obtained from ABF waveforms recorded using a Transonic aortic flow probe placed around the aortic root. The estimation errors were compared with those obtained using a windkessel model. The ARX model algorithm achieved significantly lower errors in the waveform measures, stroke volume, and cardiac output than those obtained using the windkessel model (P < 0.05).

17 ß-estradiol suppresses Helicobacter pylori-induced gastric pathology in male hypergastrinemic INS-GAS mice.

Helicobacter pylori-associated gastric cancer is male predominant and animal studies suggest that sex hormones influence gastric carcinogenesis. We investigated the effects of 17ß-estradiol (E2) or castration on H.pylori-induced gastritis in male INS-GAS/FVB/N (Tg(Ins1-GAS)1Sbr) mice. Comparisons were made to previously evaluated sham (n = 8) and H.pylori-infected (n = 8), intact male INS-GAS mice which had developed severe corpus gastritis accompanied by atrophy, hyperplasia, intestinal metaplasia and dysplasia of the epithelium within 16 weeks postinfection (all P < 0.01). Castration at 8 weeks of age had no sparing effect on lesions in uninfected (n = 5) or H.pylori-infected mice (n = 7) but all lesion subfeatures were attenuated by E2 in H.pylori-infected mice (n = 7) (P < 0.001). Notably, inflammation was not reduced but glandular atrophy, hyperplasia, intestinal metaplasia and dysplasia were also less severe in uninfected, E2-treated mice (n = 7) (P < 0.01). Attenuation of gastric lesions by E2 was associated with lower messenger RNA (mRNA) expression of interferon (IFN)-γ (P < 0.05) and interleukin (IL)-1ß (P < 0.004), and higher IL-10 (P < 0.02) as well as decreased numbers of Foxp3(+) regulatory T cells when compared with infected intact males. Infected E2-treated mice also developed higher Th2-associated anti-H.pylori IgG1 responses (P < 0.05) and significantly lower Ki-67 indices of epithelial proliferation (P < 0.05). E2 elevated expression of mRNA for Foxp3 (P < 0.0001) and IL-10 (P < 0.01), and decreased IL-1ß (P < 0.01) in uninfected, intact male mice compared with controls. Therefore, estrogen supplementation, but not castration, attenuated gastric lesions in H.pylori-infected male INS-GAS mice and to a lesser extent in uninfected mice, potentially by enhancing IL-10 function, which in turn decreased IFN-γ and IL-1ß responses induced by H.pylori.

Persistent infection of rhesus monkeys with 'Helicobacter macacae' and its isolation from an animal with intestinal adenocarcinoma.

A novel helicobacter, 'Helicobacter macacae', was previously isolated from a colony of rhesus and cynomolgus monkeys in which diarrhoea from chronic idiopathic colitis was enzootic. A survey performed in a second colony of rhesus monkeys without a history of chronic diarrhoea determined that 57 % were faecal-culture positive for Helicobacter species. Ten years after the survey, one of the animals from which 'H. macacae' had been isolated, a 23-year-old, intact male rhesus monkey (Macaca mulatta), presented with partial inappetence and progressive weight loss. Subsequent evaluation of the monkey revealed anaemia, hypoproteinaemia, hypoalbuminaemia and a palpable abdominal mass. Contrast radiography suggested partial intestinal obstruction. The animal was euthanized and a diagnosis was made of intestinal adenocarcinoma of the ileocaecocolic junction with metastasis to regional lymph nodes and liver. Microaerobic culture of caecal tissue yielded a helicobacter organism identified as 'H. macacae' by 16S rRNA gene sequencing - the same species of bacteria isolated 10 years previously. The liver, small intestine and colon were also positive by PCR for Helicobacter species. Intestinal adenocarcinoma is the most common malignancy of aged macaques. Faeces or caecal tissue from five out of five monkeys that remained from the original cohort and that were colonized with 'H. macacae' in the initial survey were positive for the organism. The apparent persistence of 'H. macacae' in these animals, the isolation of the bacterium from animals with colitis and the recognition of the importance of inflammation in carcinogenesis raise the possibility of an aetiological role in the genesis of intestinal adenocarcinoma in aged rhesus monkeys.

Characterization of cytotoxic necrotizing factor 1-producing Escherichia coli strains from faeces of healthy macaques.

Twenty-five (27 %) of 92 clinically normal macaques were found to have beta-haemolytic Escherichia coli isolated from their faeces. Five of six isolates chosen for further characterization had multiple antibiotic resistance and were PCR-positive for cytotoxic necrotizing factor 1 (cnf1) with a demonstrated cytopathic effect in vitro. By repetitive element sequence-based PCR genotyping, genetic similarity was established for selected isolates. We believe this to be the first report of E. coli strains producing CNF1 in non-human primates.

Three-dimensional conductive constructs for nerve regeneration.

The unique electrochemical properties of conductive polymers can be utilized to form stand-alone polymeric tubes and arrays of tubes that are suitable for guides to promote peripheral nerve regeneration. Noncomposite, polypyrrole (PPy) tubes ranging in inner diameter from 25 microm to 1.6 mm as well as multichannel tubes were fabricated by electrodeposition. While oxidation of the pyrrole monomer causes growth of the film, brief subsequent reduction allowed mechanical dissociation from the electrode mold, creating a stand-alone, conductive PPy tube. Conductive polymer nerve guides made in this manner were placed in transected rat sciatic nerves and shown to support nerve regeneration over an 8-week time period.

Acute respiratory distress syndrome in two rhesus macaques (Macaca mulatta).

Acute respiratory distress syndrome (ARDS) is an important and potentially life-threatening complication in humans that arises subsequent to a variety of primary insults including noxious fume inhalation, infection, and trauma. Here we describe the first two cases of ARDS reported in association with postoperative complications in rhesus macaques. In agreement with the multifactorial nature of the human syndrome, ARDS in one monkey was attributed to sepsis, whereas in the other it was ascribed to neurogenic trauma. Despite the different etiologies, both monkeys demonstrated clinical features of ARDS, including progressive dyspnea and pulmonary edema, and syndrome-defining histopathologic criteria including edema with intraalveolar neutrophils, fibrinohemorrhagic effusions with crescentic membranes, and interstitial vascular degeneration. Recognition and aggressive treatment of ARDS at an early stage may improve survival rates in dyspneic nonhuman primates with underlying extrapulmonary diseases.