Pharmacokinetics of Trazodone in Hispaniolan Parrots (Amazona ventralis).

The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.

Reference Interval Creation for Symmetric Dimethylarginine (SDMA) in Healthy Hispaniolan Amazon Parrots (Amazona ventralis) and Quaker Parrots (Myiopsitta monachus).

Renal disease is often identified as a cause of morbidity and mortality in avian patients. However, currently, early antemortem detection of renal disease in avian patients is difficult. Anatomical and physiological differences between mammals and birds mean the use of commonly employed diagnostic testing (ie, measurement of blood urea nitrogen [BUN] and serum creatinine, urinalysis, and ultrasonography) are either nondiagnostic or difficult to achieve. Symmetric dimethylarginine (SDMA) is considered a more sensitive marker for renal disease in humans, dogs, and cats. However, SDMA has not yet been assessed for diagnostic use in any psittacine species. In this study, we establish reference ranges for SDMA in both Hispaniolan Amazon parrots (Amazona ventralis, HAP) and Quaker parrots (Myiopsitta monachus, QP). Blood was collected from 23 Amazon parrots and 32 Quaker parrots maintained in research facilities. Measurement of SDMA through a commercially available immunoassay (IA-SDMA) as well as creatinine, BUN, uric acid, phosphorus, calcium, sodium, potassium, and chloride were determined through IDEXX Laboratories. Plasma SDMA concentrations ranged from 6 to 15 µg/dL and 3 to 15 µg/dL for the HAP and QP, respectively. Sex was a confounding factor for the QP population, but sex did not have a significant effect on SDMA for the HAP population. No significant correlations were identified between SDMA concentrations and other parameters in either psittacine species. Our results show proof of concept for the IA-SDMA and provide reference intervals for SDMA in HAP and QP. Further investigation is required to determine the validity of this assay and the predictive power of SDMA in the detection of renal impairment for parrots and other common companion birds.

Measuring the Level of Agreement for Lactate Measurements in Hispaniolan Amazon Parrots (Amazona ventralis) Among 2 Point-of-Care Analyzers and a Benchtop Analyzer.

Lactate is an important biochemistry analyte used in human and veterinary medicine to assess tissue perfusion and can be used as a prognostic indicator for certain disease conditions. Whereas lactate is commonly measured using "patient-side" handheld meters, these meters have not been validated for companion avian species. The purpose of this study was to measure the level of agreement between 2 commercially available point-of-care lactate meters and a laboratory benchtop blood analyzer in Hispaniolan Amazon parrots (Amazona ventralis). Blood samples were collected from 20 adult parrots at Louisiana State University by drawing 1.5 mL of blood from the right jugular vein. One drop of whole blood was used for the Lactate Plus analyzer and the remainder of the sample transferred into a lithium heparin microtainer. From the blood in the microtainer, 0.2 mL whole blood was analyzed using the epoc Blood Analysis System, and the remaining sample was centrifuged to obtain plasma that was immediately frozen at -80°C (-112°F) and submitted to the Texas A&M University Clinical Pathology Laboratory for analysis on the VITROS 4500 benchtop analyzer. Bland-Altman agreement plots and Passing-Bablok regression were used to measure the level of agreement between the methods. There was poor agreement between all 3 methods with mean percentage differences in lactate concentrations ≥22% (epoc and Lactate Plus: 33.6% [95% CI: 27-40]; epoc and VITROS 4500: 55% [95% CI:52-58]; VITROS 4500 and Lactate Plus: 22% [95% CI:16-28]). Based on these results, the point-of-care meters tested in this study are not interchangeable, and separate reference intervals were calculated for each method. Blood lactate concentrations may have more utility in tracing lactate trends over time in an individual rather than being able to utilize this information at 1 time point for disease diagnosis and prognosis.

Evaluation of Prothrombin Time and Activated Partial Thromboplastin Time in Native and Citrated Whole Blood in Hispaniolan Amazon Parrots (Amazona ventralis) With a Handheld Point-of-Care Analyzer.

Objective assessment of coagulation in birds is difficult, and traditional methods of measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT) with the use of mammalian reagents have not been validated in birds. Avian-specific reagents must be prepared from brain extract and are not practical for clinical use. The objective of this investigation was to determine whether the InSight qLabs point-of-care analyzer (Micropoint Biotechnologies Inc, Guangdong, China) could measure PT and aPTT in Hispaniolan Amazon parrots (Amazona ventralis) in native and citrated whole blood, and whether the values obtained correlated with clinical appearance and basic hematologic and biochemical parameters from the bird. The qLabs analyzer was able to measure aPTT reliably, but not PT. Activated partial thromboplastin time of citrated blood was significantly different from the aPTT measured from native whole blood (P < 0.001). On the basis of this study, the qLabs machine may be used to measure aPTT, but clinical application between avian species requires further research.

Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVE: To determine the pharmacokinetics of a solution containing cannabidiol (CBD) and cannabidiolic acid (CBDA), administered orally in 2 single-dose studies (with and without food), in the domestic rabbit (Oryctolagus cuniculus). ANIMALS: 6 healthy New Zealand White rabbits. PROCEDURES: In phase 1, 6 rabbits were administered 15 mg/kg CBD with 16.4 mg/kg CBDA orally in hemp oil. In phase 2, 6 rabbits were administered the same dose orally in hemp oil followed by a food slurry. Blood samples were collected for 24 hours to determine the pharmacokinetics of CBD and CBDA. Quantification of plasma CBD and CBDA concentrations was determined using a validated liquid chromatography-mass spectrometry (LC-MS) assay. Pharmacokinetics were determined using noncompartmental analysis. RESULTS: For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively. Adverse effects were not observed in any rabbit. CLINICAL RELEVANCE: CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater Cmax but had a shorter t1/2λ than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit.

Pharmacokinetics of Cannabidiol in the Hispaniolan Amazon Parrot (Amazona ventralis).

The purpose of this study was to determine the pharmacokinetics of cannabidiol (CBD), a potential treatment option that may alleviate pain in companion animals and humans, in the Hispaniolan Amazon parrot (Amazona ventralis). A pilot study administered a single oral dose of CBD in hemp oil at 10 mg/kg to 2 birds and 20 mg/kg to 2 birds. Because the maximum serum concentrations (Cmax) for these doses were 5.5 and 13 ng/mL, respectively, and the serum half-life was 2 hours for both groups, the doses were considered too low for clinical use in this species. Therefore, a study was designed in which 14 healthy 12-14-year-old parrots of both sexes and weighing 0.24-0.35 kg (mean, 0.28 kg) were enrolled. Seven birds were administered 60 mg/kg CBD PO, and 7 birds were administered 120 mg/kg CBD PO. Blood samples were obtained at time 0, and at 0.5, 1, 2, 3, 4, 6, and 10 hours posttreatment in a balanced incomplete block design. Quantification of plasma CBD concentrations was determined by use of a validated liquid chromatography-mass spectrometry assay. Pharmacokinetic parameters were determined by noncompartmental analysis. The areas under the curve (h·ng/mL) were 518 and 1863, Cmax (ng/ mL) were 213 and 562, and times to achieve Cmax (hours) were 0.5 and 4 for the 60 and 120 mg/kg doses, respectively. The serum half-life could not be determined in the 60 mg/kg treatment, but was 1.28 hours at 120 mg/kg. Adverse effects were not observed in any bird. The highly variable results and short half-life of the drug in Hispaniolan Amazon parrots, even at high doses, suggests that this drug formulation was inconsistent in achieving targeted concentrations as reported in other animal species.

Pilot Study of a Single Dose of Orally Administered Tapentadol Suspension in Hispaniolan Amazon Parrots (Amazona ventralis).

Tapentadol is an analgesic agent that acts as both a µ-opioid receptor agonist and a norepinephrine reuptake inhibitor. It is a common therapeutic agent in human medicine for management of acute and chronic pain, and it is currently being investigated for use in veterinary medicine. Tapentadol was evaluated in Hispaniolan Amazon parrots (Amazona ventralis) because there is only 1 other oral opioid-like analgesic agent, tramadol, which has been evaluated in an avian species. The effectiveness of tramadol after administration to a patient involves a complex physiologic metabolism and has been found to have variable pharmacokinetics between species. Because of the lack of active metabolites from tapentadol, less interspecific variation was expected. Seven Hispaniolan Amazon parrots were used to evaluate the pharmacokinetics of tapentadol after a single 30 mg/kg PO administration of a compounded 5 mg/mL tapentadol suspension. Blood samples were collected before (time 0) and 0.25, 0.5, 0.75, 1, 1.5, 3, and 6 hours after administration, following a balanced, incomplete-block design. Plasma tapentadol concentrations were measured by high-pressure liquid chromatography with mass spectrometry. Results revealed detectable plasma concentrations in only 2 of 7 birds (29%), and the bird with the highest plasma levels had a peak concentration (Cmax) of 143 ng/mL and a half-life (T 1/2) of 24.8 minutes. The variable plasma concentrations and short half-life of this drug in Hispaniolan Amazon parrots suggests that this drug would be of limited clinical use in this species; however, it is possible that this drug will be more bioavailable in other avian species.

Evaluation of Orally Administered Atorvastatin on Plasma Lipid and Biochemistry Profiles in Hypercholesterolemic Hispaniolan Amazon Parrots (Amazona ventralis).

Atorvastatin is a synthetic statin administered in its active form and used for the treatment of dyslipidemias. In the current study, the effects of atorvastatin were evaluated on plasma lipid profiles and the potential for adverse effects after once daily PO dosing of atorvastatin for 30 days in Hispaniolan Amazon parrots (Amazona ventralis). Sixteen adult parrots (10 female, 6 male) with hypercholesterolemia were used for this study. Birds were assigned to 2 groups (treatment and control) of 8 parrots each (3 male, 5 female) after balancing for age, sex, originating institution, and baseline plasma cholesterol values. Compounded atorvastatin oral suspension (10 mg/kg) was administered PO once daily via gavage into the crop. Equivalent volumes of placebo suspension were administered to the control group. Plasma biochemistry and plasma lipid profile analysis (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TGs]) were analyzed on days 0, 14, and 30. Plasma samples and HDL-C fractions were evaluated for cholesterol and TG concentrations via enzymatic assays. Subtraction of HDL-C values from total cholesterol yielded the non-HDL-C concentration for each bird. Birds were routinely assessed for appetite, activity, and urofeces. Plasma atorvastatin concentrations were obtained from 7 of 8 birds in the treatment group from banked samples. Those samples were obtained on days 14 and 30, with drug administration 6 to 8 hours before collection. No significant differences were observed in total cholesterol, HDL-C, non-HDL-C, or TG between treatment and control groups at days 0, 14, and 30. Plasma atorvastatin concentrations were variable on day 14 (0.54-5.41 ng/ mL for 6 of 7 samples, with 1 outlier of 307 ng/mL) and on day 30 (0.79-6.74 ng/mL). No adverse effects were noted in any of the birds during the study period. When dosed PO at 10 mg/kg once daily, atorvastatin did not result in significant changes to plasma lipid profiles (eg, lowering of plasma total or non-HDL-C concentrations) at any time point during this study. Future studies to investigate pharmacokinetic and pharmacodynamic properties of atorvastatin in parrots may require increased doses and/or frequency of administration.

Treatment of Exuberant Granulation Tissue in an Umbrella Cockatoo (Cacatua alba) with Strontium Radiation.

A 26-year-old female umbrella cockatoo (Cacatua alba) was presented for reoccurrence of a soft tissue mass extending from a fractured area of the rhinotheca. The mass was originally observed 12 years before, after unknown trauma. Histopathology after initial removal was consistent with inflammatory granulation tissue. The mass reoccurred 3 additional times in the same location despite surgical removal and cryogenic therapy. On the fourth surgical resection, strontium-90 radiotherapy was applied to the site immediately after the surgical procedure. No recurrence of the tissue mass from this location has been observed for almost 2 years. This case demonstrates the novel use of strontium radiotherapy to treat exuberant granulation tissue in a bird.

Morphologic and quantitative evaluation of bone marrow aspirates from Hispaniolan Amazon parrots (Amazona ventralis).

BACKGROUND: Bone marrow aspirate assessments provide valuable information about hematopoietic status and hematologic disease. Hematopoietic cell differentials and morphologies have been anecdotally described in psittacines, but quantitative studies are lacking. OBJECTIVES: We aimed to determine differential cell counts and calculate granulocyte:erythroid (G:E) ratios in bone marrow aspirates from Hispaniolan Amazon parrots and report representative morphologies of the hematopoietic cells. METHODS: Bone marrow aspirates were collected from 32 clinically healthy, captive, parrots. Peripheral blood was obtained for CBCs. Bone marrow differential cell counts (%) were determined by counting 500 cells on modified Wright's-stained smears. G:E ratios were calculated. Representative images of hematopoietic cells at all stages of development were taken. RESULTS: Of the 32 parrots sampled, 17 bone marrow samples were of sufficient cellularity and quality for evaluation. Erythroid cells comprised 68.9 ± 8.6% (total ± SD) of the hematopoietic cells and consisted primarily of early- and late-stage polychromatophilic rubricytes (43.6 ± 2.1% of total erythroid cells). Granulocytic cells comprised 28.1 ± 3.8% of the hematopoietic cells and consisted primarily of mature and band heterophils (11.9 ± 5.2% and 6.5 ± 3.4%, respectively, of total granulocytic cells). A unique morphologic finding in avian progranulocytes was the presence of multiple different granules. The G:E ratio was 0.4 ± 0.2 (median 0.4, range 0.1-0.9). Thrombocyte lineage cells could not be reliably identified and were not counted. CBC results were largely within expected limits. CONCLUSIONS: The low G:E ratios observed could be normal in this species; however, these ratios could be affected by factors related to sampling and cell identification. These findings will be a valuable resource for the diagnostic evaluation of clinical bone marrow samples from Hispaniolan Amazon parrots and could serve as a general reference for psittacine bone marrow evaluation.

Effects of Fluorescent Lighting Versus Sunlight Exposure on Calcium, Magnesium, Vitamin D, and Feather Destructive Behavior in Hispaniolan Amazon Parrots (Amazona ventralis).

Low exposure to ultraviolet light, and resulting vitamin D deficiency, has recently been linked to autism spectrum disorder in people. Captive psittacine birds that exhibit feather destructive behavior share similarities with people affected by autism spectrum disorder, such as repetitive (stereotypies) and self-harming behaviors. The metabolic and psychological effects of housing pet parrots indoors without ultraviolet B lighting are not typically considered in animal husbandry or veterinary care. Calcifediol (serum vitamin D), ionized calcium, and ionized magnesium levels were compared between 10 Hispaniolan Amazon parrots (Amazona ventralis) housed indoors and 10 Hispaniolan Amazon parrots historically housed outdoors. Although ionized calcium and magnesium levels were not significantly different, calcifediol levels were significantly greater in the colony of birds housed outdoors. Further, these 2 research colonies of individually housed birds were feather scored. Subjectively, the birds that were housed indoors had greater self-inflicted feather damage than did those housed outdoors; however, the difference was not statistically significant.

Diabetes Mellitus With Concurrent Cerebellar Degeneration and Necrosis in a Domestic Goose ( Anser anser domesticus).

A 5-year-old sexually intact male Toulouse goose ( Anser anser domesticus) was presented for ataxia, polyuria, and polydipsia. The goose was cachectic and exhibited head tremors. Results of plasma biochemical analysis and point-of-care glucometry revealed persistent hyperglycemia. Despite supportive care and oral glipizide, the goose died within 48 hours of presentation. Necropsy revealed severe pancreatic atrophy and fibrosis with regionally extensive cerebellar encephalomalacia and generalized Purkinje cell degeneration and necrosis. On a wet basis, hepatic zinc concentration was determined to be twice the reference interval by atomic absorption spectroscopy. Based on these findings, the pancreatic insufficiency with secondary diabetes mellitus was attributed to chronic zinc toxicosis. Despite birds' relative resistance to high blood glucose concentrations, prolonged hyperglycemia is suspected to have caused selective Purkinje cell degeneration and necrosis by glial activation, mitochondrial dysfunction, and glutamate toxicity, which resulted in the clinically observed motor deficits. This is consistent with experimental diabetic rat models. This case highlights the need for further investigation of the complex pathophysiology of diabetes mellitus in birds.

Compendium of Measures to Control Chlamydia psittaci Infection Among Humans (Psittacosis) and Pet Birds (Avian Chlamydiosis), 2017.

Psittacosis, also known as parrot fever and ornithosis, is a bacterial infection that can cause severe pneumonia and other serious health problems in humans. It is caused by Chlamydia psittaci. Reclassification of the order Chlamydiales in 1999 into 2 genera (Chlamydia and Chlamydophila) was not wholly accepted or adopted. This resulted in a reversion to the single, original genus Chlamydia, which now encompasses all 9 species including Chlamydia psittaci. During 2003-2014, 112 human cases of psittacosis were reported to the Centers for Disease Control and Prevention through the Nationally Notifiable Diseases Surveillance System. While many types of birds can be infected by C psittaci, in general, the literature suggests that human cases can most often occur after exposure to infected parrot-type birds kept as pets, especially cockatiels, parakeets, and conures. In birds, C psittaci infection is referred to as avian chlamydiosis. Infected birds shed the bacteria through feces and nasal discharges, and humans become infected from exposure to these materials. This compendium provides information about psittacosis and avian chlamydiosis to public health officials, physicians, veterinarians, the pet bird industry, and others concerned with controlling these diseases and protecting public health. The recommendations in this compendium provide standardized procedures to control C psittaci infections. This document will be reviewed and revised as necessary, and the most current version replaces all previous versions. This document was last revised in 2010. Major changes in this version include a recommendation for a shorter treatment time for birds with avian chlamydiosis, additional information about diagnostic testing, including genotyping, clearer language associated with personal protective equipment recommended for those caring for confirmed or exposed birds, and incorporating a grading scale with recommendations generally based on the United States Preventive Services Task Force's methods.

Rhabdomyolysis and Artifactual Increase in Plasma Bicarbonate Concentration in an Amazon Parrot (Amazona species).

A 7-year-old male Amazon parrot housed outdoors presented with acute collapse, marked lethargy, and open-mouth breathing. The patient had stiffness of the pectoral muscles, and petechiation and ecchymosis noted around the eyes and beneath the mandible. Laboratory data revealed markedly increased aspartate aminotransferase, creatine kinase, and lactate dehydrogenase activity consistent with rhabdomyolysis, as well as markedly increased plasma bicarbonate concentration. Marked clinical improvement and resolution of laboratory abnormalities occurred with fluid therapy, administration of a nonsteroidal anti-inflammatory medication, and husbandry modifications, including indoor housing and dietary alteration. A spurious increase in bicarbonate measurement as documented in equine and bovine cases of rhabdomyolysis also occurred in this avian patient and must be considered for accurate interpretation of acid-base status in exotic species presenting with consistent clinical signs.

MYCOBACTERIOSIS IN CAPTIVE PSITTACINES: A BRIEF REVIEW AND CASE SERIES IN COMMON COMPANION SPECIES (ECLECTUS RORATUS, AMAZONA ORATRIX, AND PIONITES MELANOCEPHALA).

In 2015, three psittacines were presented within 30 days, each with differing clinical signs and patient histories. A 13-yr-old male eclectus parrot (Eclectus roratus) was presented for weakness, depression, and acute anorexia. On presentation it was determined to have a heart murmur, severely elevated white blood cell count (93.9 103/µl) with a left shift (2.8 103/µl bands), and anemia (30%). Severe hepatomegaly was noted on radiographs, ultrasonography, and computed tomography. A cytological sample of the liver obtained through a fine needle aspirate revealed intracellular acid-fast bacilli identified as Mycobacterium avium. A 20-yr-old female double yellow-headed Amazon parrot (Amazona oratrix) was presented for a 1-mo history of lethargy and weight loss despite a good appetite. The parrot's total white blood cell count was 16.8 103/µl and the PCV was 35%. Following its death, a necropsy revealed a generalized granulomatous condition that involved the small intestines, lungs, liver, spleen, and medullary cavities of the long bones, with intracellular acid-fast bacilli identified as Mycobacterium genavense. The third case, an 18-mo-old female black-headed caique (Pionites melanocephala), was presented with a 1-day history of lethargy and depression. On presentation, the caique had a heart murmur, distended coelom, palpable thickening of the coelomic organs, and increased lung sounds. Following the caique's death, a complete necropsy revealed mycobacteriosis of the liver, spleen, small intestines, pericardial fat, and bone marrow. The infection was identified as Mycobacterium genavense. The importance of advances in Mycobacterium spp. identification, continued presence of this organism in captive avian populations, difficulty in obtaining a definitive antemortem diagnosis, and conflicting recommendations regarding treatment are thought-provoking areas of focus in this case series.

A Novel Surgical Approach to Avian Femorotibiotarsal Luxation Repair.

A 3-month-old male umbrella cockatoo (Cacatua alba) was presented because of acute non-weight-bearing lameness of the right leg. Marked soft tissue swelling was present around the femorotibiotarsal (stifle) joint, and the radiographic diagnosis was right medial femorotibiotarsal subluxation. Surgical management was elected, and the stifle joint was approached via a lateral parapatellar incision. Joint exploration revealed damage to the lateral meniscus, tendon of origin of the cranial tibial muscle, and cranial cruciate ligament. After debriding the disrupted meniscus, the stifle joint was anatomically reduced. The femorotibiotarsal joint was stabilized by using a lateral extracapsular suture in a modified technique using a self-tapping cortical screw in the lateral femoral condyle and a hole through the proximal tibiotarsus. The bird regained function of the femorotibiotarsal joint for 3 months after surgery, allowing sufficient time for the bird to establish a physiologic perching angle so that ankylosis occurred to maintain functionality of the leg as a unit. This combination of orthopedic techniques adapted from techniques commonly used in small companion-animal species may be considered to provide young birds with femorotibiotarsal luxations and subluxation a good quality of life despite ankylosis of the joint.