Elephant
Bibliographic
Database

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Elephant Bibliographic Database
www.elephantcare,org

References updated October 2009 by date of publication, most recent first.

Kaim, U., Paltian, V., Krudewig, C., Nieder, A., Wohlsein, P., 2009. Pulmonary aspergillosis in an African elephant (Loxodonta africana)
64. Dtsch. Tierarztl. Wochenschr. 116, 148-151.
Abstract: A 26-year-old female African elephant (Loxodonta africana) with a history of purulent pododermatitis, recurrent abdominal pain, and severe weight loss died spontaneously after a period of deteriorating disease. The main pathological finding was a severe bilateral pyogranulomatous, partially necrotizing pneumonia with numerous intralesional fungal hyphae. At microbiological examination Aspergillus spp. were isolated. The present case indicates that mycotic pneumonia should to be considered as a differential diagnosis of pulmonary disorders in elephants

Lacasse, C., Gamble, K.C., Terio, K., Farina, L.L., Travis, D.A., Miller, M. Mycobacterium szulgai osteoarthritis and pneumonia in an African elephant (Loxodonta Africana). 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  170-172. 2005.
Ref Type: Conference Proceeding
Abstract: Tuberculosis, particularly Mycobacterium bovis and M. tuberculosis, is an important health issue in zoological collections.  Zoos are a particular public health concern because of the close contact between tuberculosis-susceptible animals and humans, specifically animal handlers and visitors.¹⁶ Evidence of M. tuberculosis transmission between humans and elephants, confirmed by DNA fingerprinting, has been reported.¹³ Between 1994 and 2001, M. tuberculosis was isolated from trunk washes of captive elephants from 11 herds in the United States.¹⁷  To date, most reported cases of tuberculosis have occurred in captive Asian elephants (Elephas maximus).¹⁴ In 1997, the National Tuberculosis Working Group for Zoo and Wildlife Species partnered with the USDA to formulate the "Guidelines for the Control of Tuberculosis in Elephants." ¹⁵ This document outlines criteria for the testing, surveillance, and treatment of tuberculosis in elephants. The guidelines recommend annual monitoring of elephants by mycobacterial culture of three direct trunk washes collected over 1 wk.  Isolation of Mycobacterium avium and non-tuberculous mycobacteria from elephant trunk wash samples is common, but these organisms have not been associated with clinical disease.^14,18 This case report details clinical disease with fatal complications of an atypical mycobacterial infection in an African elephant (Loxodonta africana). In September 2003, an African elephant presented with acute, severe lameness of the left rear limb with subsequent swelling of the stifle.  Diagnostic procedures included aspiration cytology of the swelling, radiographs, and thermographic imaging.  The exact location of the injury could not be detected, but a lesion to the stifle or coxofemoral articulation was suspected.  After 13 mo of treatment, including pulse therapy with a variety of nonsteroidal anti-inflammatory drugs (NSAIDs), weekly to biweekly injections of polysulfated glycosaminoglycan, and intensive foot care efforts to treat secondary pedal lesions of both rearlimbs, the animal died acutely.  Gross necropsy revealed granulomatous osteomyelitis with necrosis/loss of the femoral head and acetabulum and pulmonary granulomas.  Both of these lesions contained acid-fast bacteria on cytology. While awaiting confirmatory culture results, quarantine procedures were established for the elephant facility and a program was established to screen all zoo personnel in close contact with the elephant or who participated in the necropsy.  All personnel were tested by the Chicago Department of Public Health without documented conversion. Mycobacterium szulgai was ultimately cultured from both coxofemoral and pulmonary lesions. Mycobacterium szulgai is an uncommon nontuberculous mycobacterium that is usually isolated from pathologic lesions in humans.²¹ This bacterial species was first identified in 1972.¹¹ The lungs are the main locality for pathologic manifestation in humans and several cases have been in patients with acquired immunodeficiency syndrome.^9,20,21 Infection due to M. szulgai most frequently produces thin-walled cavities in lungs resembling tuberculosis.⁴ Other documented sites of infection include the skin, bone, and tendon sheath (causing a carpal tunnel syndrome).^{2,9,10,12,19,20}  Intra-operative contamination from ice water has led to M. szulgai keratitis after laser-assisted ophthalmic surgeries^.6 A case of disseminated disease in a previously healthy young human has been reported.⁵  No evidence of human-to-human transmission of this organism has been documented and human cases are believed to originate from environmental sources.¹²  The natural habitat of the organism is unknown, but previous reports suggest an association of the bacteria with water of swimming pools and fish tanks.^1,21 The organism has been cultured from a snail and tropical fish.^1,3 No standard recommendation for the treatment of M. szulgai infection currently exists.  In general, triple antibiotic therapies used in standard mycobacterial treatments are reported with a low rate of relapses and sterilization of sputum cultures within a mean of 3 mo.³ Pulmonary lesions in this elephant were chronic; it was not possible to determine when initial infection occurred. Infection could have occurred in captivity or in the wild prior to captivity. Three trunk washes over the past year had been negative for mycobacterial culture. Osteomyelitis in the hip may have developed secondary to hematogenous spread from the lungs with the acute lameness resulting from a pathologic fracture associated with this infection. Alternatively, though considered less likely, a traumatic fracture of the hip could have occurred, with bacterial inoculation and secondary osteomyelitis as a result of increased blood flow to the site. The source of infection for this elephant remains unknown.  Prevalence of this organism in the natural habitat or captive environment of the elephants has not been previously documented.
LITERATURE CITED
1 Abalain-Colloc, M.L., D. Guillerm, M. Salaun, S. Gouriou, V. Vincent, and B. Picard.  2003.  Mycobacterium szulgai isolated from a patient, a tropical fish, and aquarium water.  Eur. J. Clin. Microbiol. Infect. Dis.  22: 768-769.
2.Cross, G.M., M. Guill, and J.K. Aton.  1985.  Cutaneous Mycobacterium szulgai infection. Arch. Dermatol. 121: 247-249.
3. Davidson, P.T. 1976. Mycobacterium szulgai: a new pathogen causing infection of the lung.  Chest 69: 799- 801.
4. Dylewski, J.S., H.M. Zackon, A.H. Latour, and G.R. Berry.  1987.  Mycobacterium szulgai: an unusual pathogen.  Rev. Infect. Dis.  9: 578-580.
5. Gur, H., S. Porat, H. Haas, Y. Naparstek, and M. Eliakim.  1984.  Disseminated mycobacterial disease caused by Mycobacterium szulgai. Arch. Intern. Med. 144: 1861-1863.
6.Holmes, G.P., G. Bond, R.C. Fader, and S.F. Fulcher.  2002. A cluster of cases of Mycobacterium szulgai keratitis that occurred after laser-assisted in situ keratomileusis.  Clin. Infect. Dis. 34: 1039-1046.
7.Horusitzky, A., X. Puechal, D. Dumont, T. Begue, M. Robineau, and M. Boissier.  2000.  Carpal tunnel syndrome caused by Mycobacterium szulgai. J. Rheumatol 27: 1299-1302.
8.Hurr, H., and T. Sorg.  1998.  Mycobacterium szulgai osteomyelitis.  J. Infect.  37: 191-192.
9.Luque, A.E., D. Kaminski, R. Reichman, and D. Hardy. 1998.  Mycobacterium szulgai osteomyelitis in an AIDS patient. Scand. J. Infect. Dis. 30: 88-91.
10.Maloney, J.M., C.R. Gregg, D.S. Stephens, F.A. Manian, and D. Rimland.  1987.  Infections caused by Mycobacterium szulgai in humans.  Rev. Infect. Dis.  9: 1120-1126.
11.Marks, J., P.A. Jenkins, and M. Tsukamura.  1972.  Mycobacterium szulgai: a new pathogen.  Tubercle 53: 210.
12.Merlet, C., S. Aberrane, F. Chilot, and J. Laroche.  2000.  Carpal tunnel syndrome complicating hand flexor tenosynovitis due to Mycobacterium szulgai. Joint Bone Spine 67: 247-248.
13.Michalak, K., C. Austin, S. Diesel, J.M. Bacon, P. Zimmerman, and J. N. Maslow.  1998. Mycobacterium tuberculosis infection as a zoonotic disease: transmission between humans and elephants. Emerg. Infect. Dis. 4: 283-287.
14.Mikota, S.K., R.S. Larsen, and R.J. Montali.  2000.  Tuberculosis in elephants in North America.  Zoo Biol. 19: 393-403.
15.National Tuberculosis Working Group for Zoo and Wildlife Species. 2000. Guidelines for the control of tuberculosis in elephants.  USDA Animal and Plant Health Inspection Services.
16.Oh, P., R. Granich, J. Scott, B. Sun, M. Joseph, C. Stringfield, S. Thisdell, J. Staley, D. Workman-Malcolm, L. Borenstein, E. Lehnkering, P. Ryan, J. Soukup, A. Nitta, and J. Flood.  2002.  Human exposure following  Mycobacterium tuberculosis infection of multiple animal species in a metropolitan zoo.  Emerg. Infect. Dis. 8: 1290-1293.
17.Payeur, J.B., J.L. Jarnagin, J.G. Marquardt, and D.L. Whipple.  2002.  Mycobacterial isolations in captive elephants in the United States.  Ann. N.Y. Acad. Sci. 969: 256-258.
18.Shojaei, H., J.G. Magee, R. Freeman, M. Yates, N.U. Horadagoda, and M. Goodfellow.  2000. Mycobacterium elephantis sp. nov., a rapidly growing non-chromogenic Mycobacterium isolated from an elephant.  Int. J. Syst. Evol. Microbiol.  50: 1817-1820.
19.Stratton, C.W., D.B. Phelps, and L.B. Reller.  1978.  Tuberculoid tenosynovitis and carpal tunnel syndrome caused by Mycobacterium szulgai.  Am. J. Med.  65: 349-351.
20.Tappe, D., P. Langmann, M. Zilly, H. Klinker, B. Schmausser, and M. Frosch.  2004.  Osteomyelitis and skin ulcers caused by Mycobacterium szulgai in an AIDS patient.  Scand. J. Infect. Dis. 36: 883-885.
21.Tortoli, E., G. Besozzi, C. Lacchini, V. Penati, M.T. Simonetti, and S. Emler.  1998.  Pulmonary infection due to Mycobacterium szulgai, case report and review of the literature.  Eur. Respir. J.  11: 975-977.

Neiffer, D.L., Miller, M.A., Weber, M., Stetter, M., Fontenot, D.K., Robbins, P.K., Pye, G.W., 2005. Standing sedation in African elephants (Loxodonta africana) using detomidine-butorphanol combinations. J. Zoo. Wildl. Med. 36, 250-256.
Abstract: Standing sedation was provided for 14 clinical procedures in three African elephants (Loxodonta africana) managed by combined protected and modified-protected contact and trained through operant conditioning. An initial hand-injection of detomidine hydrochloride and butorphanol tartrate at a ratio of 1:1 on a microg:microg basis was administered intramuscularly, with a dosage range of 50-70 mg (12.9-19.7 microg/kg) for each drug. The initial injection resulted in adequate sedation for initiation and completion of eight procedures, whereas supplemental doses were required for the remaining procedures. The dosage range for the supplemental injections of each drug was 4.0-7.3 microg/kg. Initial effect was noted within 3.0-25 min (mean = 11.6 min, SD +/- 5.9 min), with maximal effect occurring at 25-30 min for those procedures not requiring supplementation. In all but one procedure, this effect was maintained until the end of the procedure, which ranged from 47 to 98 min (mean = 74.7 min, SD +/- 18.8 min). No cardiac or respiratory depression was appreciated. Recovery after administration of reversal agents was rapid and complete, ranging from 2 to 20 min (mean = 9.0 min, SD +/- 7.0 min). On the basis of the authors' experience, recommended dosage ranges for reversal agents would be intravenous yohimbine (73.4-98.5 microg/kg), intravenous naltrexone (48.9-98.5 microg/kg), and intramuscular naltrexone (73.4-98.5 microg/kg). Approximately one-third to one-half of the total naltrexone dose should be administered intravenously. Mild adverse side effects limited to the gastrointestinal tract were observed in association with five procedures including abdominal distention with or without transient anorexia. Administration of reversal agents, encouraging exercise and water consumption, and administration of flunixin meglumine were helpful in the resolution of signs. In addition to gastrointestinal signs, slight ataxia was observed before initiation of surgical stimulation during one procedure in which 19.7 microg/kg of each drug was administered. On the basis of the procedures that did not require supplementation to initiate treatment and taking into consideration the potential for ataxia at higher doses, a starting dosage range of 14.7-16.2 microg/kg of both detomidine and butorphanol in a ratio of 1:1 on a microg:microg basis administered i.m. simultaneously is recommended

Suedmeyer, W.K., Oosterhuis, J., Kollias, G., Fagan, D., Hornoff, B., Dodam, J., Shafford, H. Elephant restraint device assisted anesthesia in an African elephant (Loxodonta africana). 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  189-191. 2005.
Ref Type: Conference Proceeding
Abstract: Modern elephant management programs often include the use of protected contact. This allows improved safety for the elephant staff but may limit access to medical conditions occurring in elephants.
A 27-yr-old female African elephant (Loxodonta africana) weighing an estimated 3,700 kg was anesthetized for evaluation of a chronic, progressive, fistulous tract of the left ventral mandible. The mandible was routinely cultured, flushed with diluted peroxide, chlorhexidine, betadine solution, or alternating antibiotics, based on microbial sensitivities. To properly assess the left mandible, the elephant had to be placed in right lateral recumbency, which was accomplished with the use of a commercially available rotational elephant restraint device (ERD). Because of the protected contact management program, right lateral recumbency could not be guaranteed at the time of immobilization. Malpositioning, tusk fracture and/or related injury could occur upon recumbency without the additional control afforded by the ERD. The ERD is a hydraulically operated unit that comfortably restrains an elephant, minimizing safety risks to the animal and staff. The ERD consists of one solid wall, three side panels, and hinged floor. The ends of the restraint are closed with moveable shift doors. The three side panels can be moved independently depending upon the size of the animal and are further subdivided with moveable "subpanels" to allow direct access to various areas of the animal. In addition, support straps help gently stabilize limbs when performing medical procedures. The unit is positioned within the elephant holding facility at the Kansas City Zoo. The unit was installed in 1994 during renovation of the elephant exhibit, whereupon the elephant management program was changed from free-contact to protected contact. The ERD is utilized for reproductive assessments, semen collection, transabdominal ultrasound, evaluation of integumentary wounds, ophthalmic and aural examination, and administration of injectable medications. However, no elephant had been anesthetized and rotated in the restraint. The affected animal could not be guaranteed to re-enter the ERD once rotated, but would enter and station in the ERD on a daily basis. Because of this, a conspecific was conditioned to allow rotation without the use of sedatives or tranquilizers, to prepare for the actual immobilization. Adjustments in strap placement, cushioning, critical evaluation of mechanical stability, and placement of hydraulic panels allowed staff to prepare for the actual immobilization, minimizing complications. The elephant was conditioned to enter and station in the ERD. After strapping the distal limbs, thorax and caudal abdomen for support, the elephant was immobilized with a combination of 3,000 IU of hyaluronidase (O'Brien Pharmacy, Kansas City, MO USA), 10 mg acepromazine maleate, and 7 mg etorphine hydrochloride (Wildlife Pharmaceuticals Inc., Fort Collins, CO USA) via pole syringe. Close monitoring of induction was performed and when stage III anesthetic plane was achieved, the elephant was rotated into right lateral recumbency, elevating the elephant 6 feet above the floor. No voluntary movement of the animal was noted while the restraint was in motion. Direct arterial blood pressure, indirect oscillometric blood pressure, blood gases, respiratory rate, excursion characteristics, cardiac rate and rhythm, and pulse oximetry was routinely monitored during the procedure. Anesthesia was maintained with intermittent boluses of etorphine hydrochloride. Intravenous physiologic fluids (lactated Ringers solution) were maintained via an i.v. aural catheter, and insufflation with oxygen was provided on a continual basis. Oral examination and palpation demonstrated an incomplete transverse fissure of the left mandibular molar, intact gingival, and proper dental occlusion with the upper arcade.  Digital radiographs of the left mandible were performed based on exposures obtained with a set of skeletonized jaws. Advantages of this diagnostic modality are the immediate imaging results, portability, and digital imaging and storage, and does not require a developer or fixative. Adjustments in radiographic angle and technique were made to obtain the best diagnostic image. Radiographic imaging demonstrated a sequestrum consisting of a fractured enamel plate  ²of the mandibular molar with a fistulous tract that coursed ventrally to communicate through the skin. The elephant was elevated 6 feet above the ground, which presented unique challenges. Because of the relatively small operating space, intubation was not possible, but insufflation was readily achieved and successful based on pulse oximetry trends. A commercial lift was utilized to elevate two large-animal circle anesthetic units to the level of the elephant's head. During immobilization the legs were cushioned and restraint straps removed to lessen the potential for occlusive damage to the tissues. The ERD allows an elephant to be positioned in either right or left lateral recumbency.
Upon completion of diagnostic procedures, the narcotic agent was reversed with 1,400 mg naltrexone hydrochloride (Zoopharm, Laramie, WY USA) administered 25% intravenously and 75% subcutaneously. The elephant awoke within 90 sec and was rotated to a standing position within the restraint. Thereafter, the elephant was confined in the restraint for approximately 45 min, until no untoward effects were likely to occur. The elephant was released from the restraint and resumed normal eating and drinking within 8 hr, and voluntarily entered the restraint within 2 wk following the procedure. The elephant was stable throughout the procedure; however, a predetermined objective for mean arterial blood pressures (<200 MAP) was not achieved. Hyaluronidase was utilized to promote rapid absorption of the narcotic and neuroleptic agents.³ Acetylpromazine was used to maintain peripheral perfusion by reducing the hypertensive effects of etorphine,¹ which has been documented in previous immobilizations of African elephants.^3-5 Etorphine hydrochloride, a powerful narcotic agent, has been successfully used as an immobilizing agent in both wild and captive African elephants.^3-5 Use of an ERD allowed full control of the immobilization, increasing safety for personnel, preventing injury to the elephant, and positioning the left mandible on the dorsal plane. Disadvantages are the elevated height of the elephant, relatively small operating space, and disrupted line of sight communication. A second procedure will be performed in the near future to address the fracture and subsequent sequestrum diagnosed during the first immobilization. The elephant is currently being conditioned to allow restraint in a holding stall that will allow greater access to the oral cavity and surgical manipulation of the affected mandible.
ACKNOWLEDGMENTS
We thank the staff of the Kansas City Zoological Park for their care, concern, and expertise in helping make this procedure a success.
LITERATURE CITED
1 Booth, N.H. Psychotropic agents. In: Booth, N.H., and R.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics.  W.B. Saunders, Co., Philadelphia, PA. P. 329.
2 Fagan, V.D.A., J.E. Oosterhuis, and A. Roocraft. 2001. Captivity disorders in elephants: impacted molars and broken tusks. Der Zoologische Garten 71:281-303.
3 Honeymoon, V.L., G.R. Pettifer, and D.H. Dyson. 1992. Arterial blood pressure and blood gas values in normal standing and laterally recumbent African (Loxodonta africana) and Asian (Elephas maximus)    elephants. J. Zoo Wildl. Med. 23:205-210.
4. Kock, R.A., P. Morkel, and M.D. Kock. 1993. Current immobilization procedures used in elephants. In: Fowler,
M.E. (ed.).  Zoo and Wild Animal Medicine: Current Therapy 3. W.B. Saunders Co., Philadelphia, PA.  Pp. 436-441.
5 Raath, J.P. 1999. Relocation of African elephants. In: Fowler, M.E., and R.E. Miller (eds.). Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Co., Philadelphia, PA.  Pp. 525-533.

Vinogradov, I.V., Kochneva, G.V., Malkova, E.M., Shchelkunov, S.N., Riabchikova, E.I., 2005. [Intranasal infection in mice inoculated with cowpox virus strain EP-2 isolated from the elephant]
579. Vopr. Virusol. 50, 37-42.
Abstract: The specific features of reproduction of EP-2 strain of cowpox virus (CPV) were studied in intranasally infected BALC/C mice by light and electron microscopy. Virus replication was found in the ciliated, intercalary, basal, and goblet cells (the nasal respiratory area), basal and supporting cells (the nasal olfactory area), ciliated, intercalary, goblet cells (the tracheal and bronchial epithelium), and collagen-producing, Schwann's, endothelial, smooth muscle, and adventitial cells. It has been shown that the CPV strain EP-2 locally replicates in the nasal cavity, trachea, and large bronchi and that there is no generalized infection

Dangolla, A., Silva, I., Kuruwita, V.Y., 2004. Neuroleptanalgesia in wild Asian elephants (Elephas maximus maximus)
662. Vet. Anaesth. Analg. 31, 276-279.
Abstract: OBJECTIVE: To evaluate the suitability of etorphine with acepromazine for producing prolonged neuroleptanalgesia in wild Asian elephants. ANIMALS: Ten adult wild elephants (four males, six females), free-roaming in the jungles of the north-western province of Sri Lanka. MATERIALS AND METHODS: Ten wild elephants were tranquilized for attachment of radio transmitter collars from September to November 1997, using Large-Animal Immobilon (C-Vet Veterinary Products, Leyland, UK), which is a combination of etorphine (2.45 mg mL(-1)) and acepromazine (10 mg mL(-1)). This was injected using projectile syringes fired from a Cap-Chur gun (Palmer Chemical Co. Inc., Atlanta, USA). A volume of 3.3 (2.5-4.5) mL Immobilon (6.12-11.02 mg of etorphine and 25-45 mg acepromazine) was injected intramuscularly after body mass estimation of individual elephants. RESULTS: The body condition of all darted elephants was good, and the mean (minimum-maximum) shoulder height was 225 (180-310) cm. The average approximate distance to elephants at firing was 26 (15-50) m. The average time to recumbency after injection was 18 (15-45) minutes. Nine out of 10 elephants remained in lateral recumbency (and did not require additional dosing) for a period of 42 (28-61) minutes. The respiratory and heart rates during anaesthesia were 7 (4-10) breaths and 52 (40-60) beats minute(-1), respectively. An equal volume (8.15-14.67 mg) of diprenorphine hydrochloride (Revivon, 3.26 mg mL(-1) diprenorphine; C-Veterinary Products, Leyland, UK) was given intravenously when the procedure was completed. Recovery (return to standing position) occurred in 6 (2-12) minutes after diprenorphine injection. Immediately afterwards, all elephants slowly retreated into the jungle without complications. Continuous radio tracking of the animals involved in this study indicated no post-operative mortality for several months after restraint. CONCLUSIONS/CLINICAL RELEVANCE: Etorphine-acepromazine combinations can be used safely in healthy wild Asian elephants for periods of restraint lasting up to 1 hour

Smith, T. Zoo research guidelines: Monitoring stress in zoo animals.  2004. London, Federation of Zoological Gardens of Great Britain and Ireland.
Ref Type: Report

Stringfield, C.E., Oh, P., Granich, R., Scott, J., Sun, B., Joseph, M., Flood, J., Sedgwick, C.J. Epidemiologic investigation of a Mycobacterium tuberculosis infection of multiple animal species in a metropolitan zoo. 2004 PROCEEDINGS AAZV, AAWV, WDA JOINT CONFERENCE.  46-48. 2004.
Ref Type: Conference Proceeding
Abstract: From 1997 to 2000, six cases of Mycobacterium tuberculosis (TB) infection were diagnosed in three species of animals at, or recently originating from, the Los Angeles Zoo. Restriction fragment length polymorphism (RFLP) analysis showed that five of six animal isolates shared an identical IS6110 pattern, with the sixth differing only by one additional band. A multiinstitutional epidemiologic investigation was conducted to identify and interrupt possible transmission among the animal cases, and to screen personnel for active TB infection and TB skin-test conversion.
Animal Cases
In April and October of 1994, Asian elephant (Elephas maximus) #1 and Asian elephant #2 arrived at the Los Angeles Zoo from a private elephant facility where they had lived together. They were housed together at the zoo until November of 1996 when elephant #2 was returned to the facility for several months before transfer to another zoo. In the spring of 1997, Elephant #1 (30 yr old) died of salmonellosis, with M. tuberculosis found in granulomatous lymph node lesions from the thoracic and abdominal cavities, and Elephant #2 (30 yr old) was found to have a positive trunk wash culture for M. tuberculosis. In July of 1998, one of a closed herd of three Rocky Mountain goats (Oreamnos americanus) consisting of a sire and two offspring, died of pulmonary M. tuberculosis at 6 yr of age. The goat's asymptomatic herdmates were screened and had negative chest radiographs and tracheal wash cultures, but one of the two goats was positive on tuberculin skin-test. In October of 1998, a clinically normal Black rhinocerus (Diceros bicornis) was diagnosed with Mycobacerium tuberculosis after a positive skin test and nasal wash culture. In the winter of 1998, the two remaining goats were evaluated again with negative chest radiographs and tracheal wash cultures. However, 1 yr later, both were humanely euthanatized at 8 and 12 yr of age due to clinical evidence of tuberculosis on chest radiographs (both animals), and active clinical signs in one (neither were able to be orally treated). In January of 2001, a rhino was humanely euthanatized after a protracted illness that was nonresponsive to aggressive treatment. The rhino was found to have severe multifocal hemosiderosis and atypical mycobacterial infection in her lungs, with no M. tuberculosis  cultured. This animal had been treated with oral Isoniazid and Rifampin for 1 yr, cultured routinely, and was never culture positive again.
 Epidemiologic Investigation
Investigators examined medical and location histories of the affected animals, animal handling practices, health-care procedures, and performed an infection control assessment of the animal compounds and health-care facilities (including measuring air flow in the compounds by smoke testing). We conducted a review of zoo employee medical records for evidence of TB symptoms, tuberculin skin-test results, and chest radiograph information. A list of current and former employees was cross-matched with reported TB cases in the California state registry from 1985 to 2000. As part of the annual occupational health screening in June of 2000, zoo employees underwent questioning regarding TB symptoms, received tuberculin skin tests, and completed a questionnaire on medical history, job type, and history of contact with the infected animals.
Epidemiologic Findings
No common cross-species contact outside the animal compounds and no contact with an infectious human were found. The distance at which the public was kept from the animals and the distance of the compounds from each other (the elephant compound was 27 meters from the rhino compound and the goat compound was 90 m from both) suggests that direct transmission was unlikely. No active TB cases in humans were found, and no matches were found in the database of reporte d cases. The RFLP analysis of this strain of M. tuberculosis matched that of three elephants with which #1 and #2 were housed at a private elephant facility from September of 1993-February of 1994.1 We hypothesize that elephants #1 and #2 were infected at the private facility and were shipped with latent M. tuberculosis infection in 1994, subsequently infecting the black rhino and Mountain goats at the Los Angeles Zoo.
Of interest, animal caretaking and animal contact were not associated with a positive tuberculin skin-test, while groundskeepers were found to have an increased risk of tuberculin skin-test conversion compared with other job categories. Employees attending the elephant necropsy and employees who trained elephants were more likely to have tuberculin skin-test conversion than those who did not.
Conclusion
This is the first documented human and veterinary epidemiologic investigation of Mycobacterium tuberculosis affecting multiple species in a zoo. ² No evidence of transmission from humans to animals or active infections in humans were found. Genotyping evidence strongly suggests transmission from one species to another, although no evidence of transmission was discovered. Human tuberculin skin-test conversions associated with the elephants were most likely due to lack of respiratory protection for these employees when the risk of TB infection was not known. The finding that groundskeepers and not animal handlers were associated with a higher risk of tuberculin skin-test conversion was surprising, and we hypothesized that this may have to do with groundskeepers as a group being more likely to have
been born outside of the United States.
Control measures to eliminate the spread of disease to people and animals were undertaken immediately and throughout this outbreak, and no further cases of M. tuberculosis have been diagnosed at the zoo in the past 3 yr despite ongoing surveillance. Four elephants and three rhinos that had direct contact with the infected animals remain TB negative by trunk and nasal wash culture methods as outlined by the USDA for elephant TB surveillance. Methods of indirect transmission in mammalian zoo species and causes of variability in infection and morbidity within and among species warrant further investigation. Ongoing vigilance, occupational health programs and infection control measures in potentially exposed animals are recommended to prevent ongoing transmission of M. tuberculosis in zoo settings.
Acknowledgments
The authors thank the Animal Care and Animal Health staff of the Los Angeles Zoo who cared so well for these animals, and the veterinarians (including consulting pathologists), technicians, and medical records staff who collected, analyzed, and organized the clinical data. We could not have performed this evaluation without Sue Thisdell, Safety Officer at the Los Angeles Zoo; Jothan Staley and Donna Workman-Malcom of the City of Los Angeles Occupational Health Services Division; Lee Borenstein, Elenor Lehnkering, Patrick Ryan, Jeanne Soukup, and Annette Nita of the Los Angeles County Department of Health Services; and Diana Whipple for her RFLP expertise.
LITERATURE CITED
1. Mikota, S.K., L. Peddie, J. Peddie, R. Isaza, F. Dunker, G. West, W. Lindsay, R.S.Larsen, M. D. Salman, D. Chatterjee, J. Payeur, D. Whipple, C. Thoen, D. Davis, C. Sedgwick, R.J. Montali, M. Ziccardi, J. Maslow. 2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in captive asian elephants (Elephas maximus). J. Zoo Wildl. Med. 32: 1-16.
2. Oh, P., R. Granich, J. Scott, B. Sun, M. Joseph, C. Stringfield, S. Thisdell, J. Staley, D. Workman-Malcolm, L. Borenstein, E. Lehnkering, P. Ryan, J. Soukup, A.Nitta, J. Flood. 2002. Human exposure following Mycobacterium tuberculosis infection of multiple animal species in a metropolitan zoo. Emerging Infectious Diseases. 8 (11): 1290-1293.orte

Suarez, R.K., Darveau, C.A., Childress, J.J., 2004. Metabolic scaling: a many-splendoured thing
656. Comp Biochem. Physiol B Biochem. Mol. Biol. 139, 531-541.
Abstract: Animals at rest and during exercise display rates of aerobic metabolism, VO2, that represent mainly the sum of mitochondrial respiration rates in various organs. The relative contributions of these organs change with physiological state such that internal organs such as liver, kidney and brain account for most of the whole-body VO2 at rest, while locomotory muscles account for >90% of the maximum rate, VO2max, during maximal aerobic exercise. Mechanisms that regulate VO2 are complex and the relative importance of each step in a series, estimated by metabolic control analysis, depends upon the level of biological organization under consideration as well as physiological state. Despite this complexity, prominent single-cause models propose that metabolic rates are supply-limited and that the scaling of supply systems provides a sufficient explanation for the allometric scaling of metabolism. We argue that some assumptions, as well as current interpretations of the meaning (or consequences) of these constraints are flawed, i.e., elephants do not have lower mass-specific basal or maximal rates of aerobic metabolism because their mitochondria are more supply-limited than those of shrews. Animals do not violate the laws of physics, and the allometric scaling of supply systems would be expected, to some extent, to be matched by capacities for (and rates of) energy expenditure. But life is not so simple. Animals are so diverse that to do justice to metabolic scaling, it is also necessary to consider the scaling of energy expenditure. It is by doing so that models of metabolic scaling can be consistent with current paradigms in metabolic regulation and accommodate the range of inter- and intraspecific exponents found in nature. The "allometric cascade," a first attempt at such an accounting, was a source of great satisfaction to Peter Hochachka. It was the last door that he helped open to comparative physiologists before he said goodbye

Isaza, R., Behnke, B.J., Bailey, J.K., McDonough, P., Gonzalez, N.C., Poole, D.C., 2003. Arterial blood gas control in the upright versus recumbent Asian elephant. Respir Physiolo Neurobiol 134, 169-176.
Abstract: In the elephant, there is concern that lateral recumbency (LR) impairs respiratory muscle and lung function resulting in clinically significant arterial hypoxemia. Using healthy adult female Asian elephants (Elephas maximus, n=6), the hypothesis was tested that, given the O₂ binding characteristics of elephant blood, substantial reductions in arterial O₂ pressure PaO₂   in LR could be tolerated without lowering arterial O₂ content appreciably. Fifteen minutes of LR decreased PaO₂ from 103+/-2 (upright, U) to 77+/-4 mmHg (P<0.05) and hemoglobin O₂ saturation (U, 97.8+/-0.1, LR, 95.3+/-0.5%, P<0.05). However, due to a recumbency-induced hemoconcentration, arterial O₂  content was unchanged (U, 18.2+/-2.4, LR, 18.3+/-2.1 ml O₂  per 100 ml). In addition, there was a mild hyperventilation in LR that reduced arterial CO₂ pressure (PCO₂₎ from 39.4+/-0.3 to 37.1+/-1.0 mmHg (P<0.05). These data indicate that the Asian elephant can endure at least short periods of LR without lowering arterial O₂  content.

Potters, D., Seghers, M., Muyldermans, G., Pie´rard, D., Naessens, A., Lauwers, S., 2003. Recovery of Mycobacterium elephantis from sputum of a patient in belgium. Journal of Clinical Microbiology 41, 1344.
Abstract: Mycobacterium elephantis was isolated from a human respiratory specimen in April 1999, demonstrating its presence in Europe. The biochemical reaction results, antimicrobial susceptibility pattern, and sequence data for this strain are all in agreement with those of M. elephantis strains isolated previously from other continents.

West, J.B., Fu, Z., Gaeth, A.P., Short, R.V., 2003. Fetal lung development in the elephant reflects the adaptations required for snorkeling in adult life. Respir Physiol Neurobiol 138, 325-333.
Abstract: The adult elephant is unique among mammals in that the pleural membranes are thickened and the pleural cavity is obliterated by connective tissue. It has been suggested that this peculiar anatomy developed because the animal can snorkel at depth, and this behavior subjects the microvessels in the parietal pleura to a very large transmural pressure. To investigate the development of the parietal pleura, the thickness of the endothoracic fascia (ET) was measured in four fetal African elephants of approximate gestational age 111-130 days, and the appearances were compared with those in human, rabbit, rat and mouse fetuses of approximately the same stage of lung organogenesis. The mean thicknesses of ET in the elephant, human, rabbit, rat and mouse were 403, 53, 29, 27 and 37 microm, respectively. This very early development of a thick parietal pleura in the elephant fetus is consistent with the hypothesis of a long history of snorkeling in the elephant's putative aquatic ancestors. Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0623, USA. jwest@ucsd.edu

 2002. Large Animal Internal Medicine. Mosby, St.Louis.

Payeur, J.B., Jarnagin, J.L., Marquardt, J.G., Whipple, D.L., 2002. Mycobacterial isolations in captive elephants in the United States. Ann N Y Acad Sci 969, 256-258.
Abstract: Interest in tuberculosis in elephants has been increasing over the past several years in the United States. Several techniques have been used to diagnose mammalian tuberculosis. Currently, the test considered most reliable for diagnosis of TB in elephants is based on the culture of respiratory secretions obtained by trunk washes.

Pitts, N.I., Mitchell, G., Raath, C., 2002. Succinylcholine overdose in the African elephant (Loxodonta africana) and impala (Aepyceros melampus): pharmacokinetics, pharmacodynamics and physiological responses. South African Journal of Science 98, 581-588.
Abstract: We investigated the mechanism of the delayed effect of succinylcholine (SuCh) in elephants, by correlating the plasma concentration of SuCh with alterations in respiratory and cardiovascular function and with changes in plasma markers of metabolism. These changes were compared with those in impalas, following a lethal SuCh dose in each species. Total entry of SuCh into the circulation (cumulative dose) and total exposure of neuromuscular receptors to unhydrolysed SuCh (area under curve of plasma, SuCh vs. time), were determined. Absorption of intramuscular SuCh was slower, and the cumulative dose lower in elephant than impala, but exposure to intact SuCh was similar in both. SuCh produced apnoea, a fall in PaO2 and pH, and rises in the PaCO2 and plasma catecholamine and cortisol concentrations, and variable cardiovascular responses. These changes took longer to develop in elephant than impala, but in both species death was associated with metabolic consequences of severe hypoxia. We conclude that the delayed effect of SuCh in elephant does not arise from differences in SuCh pharmacodynamics between the species but can be attributed to different pharmacokinetics, the lower mass-specific metabolic rate of the elephant, and its greater tolerance of severe metabolic changes before death results.

West, J.B., 2002. Why Doesn't the Elephant Have a Pleural Space? News Physiol Sci 17, 47-50.
Abstract: The elephant is the only mammal whose pleural space is obliterated by connective tissue. This has been known for 300 years but never explained. The elephant is also the only animal that can snorkel at depth. The resulting pressure differences require changes in the pleural membranes and pleural space.

Ball, R.L. Ultrasound Evaluation of the Pleura Space and Associated Connective Tissue in the Asian Elephant (Elephas maximus). A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001.  245. 2001. Vienna, Austria, Schuling Verlag. 2001.
Ref Type: Conference Proceeding

Lekeux, P., Duvivier, D.H. Aerosol therapy. IVIS . 2001.
Ref Type: Electronic Citation

West, J.B., 2001. Snorkel breathing in the elephant explains the unique anatomy of its pleura. Respiratory Physiology 126, 1-8.
Abstract: It has been known for over 300 years that the anatomy of the elephant lung is unique among mammals in that the pleural cavity is obliterated by connective tissue. However no satisfactory explanation has been advanced. Recent studies suggest that the elephant has an aquatic ancestry and the trunk may have developed for snorkeling. In addition, the modern day elephant is the only mammal that can remain submerged far below the surface of the water while snorkeling. The resulting differences of pressures within the thorax mean that the small blood vessels of the pleura are in great danger of rupturing or causing severe edema. The same distribution of pressures occurs when the animal raises water inside its trunk prior to drinking although in this case the pressure differences are relatively short-lived. Evolution has provided a remarkable solution to this problem by replacing the normally delicate parietal and visceral pleurae by dense connective tissue, and separating the two pleurae by loose connective tissue to allow some sliding movement.

Shojaei, H., Magee, J.G., Freeman, R., Yates, M., Horadagoda, N.U., Goodfellow, M., 2000. Mycobacterium elephantis sp. nov., a rapidly growing non-chromogenic Mycobacterium isolated from an elephant. International Journal of Systematic and Evolutionary Microbiology 50, 1817-1820.
Abstract: A strain isolated from a lung abscess in an elephant that died from chronic respiratory disease was found to have properties consistent with its classification in the genus Mycobacterium. An almost complete sequence of the 16S rDNA of the strain was determined following the cloning and sequencing of the amplified gene. The sequence was aligned with those available on mycobacteria and phylogenetic trees inferred by using three tree-making algorithms. The organism, which formed a distinct phyletic line within the evolutionary radiation occupied by rapidly growing mycobacteria, was readily distinguished from members of validly described species of rapidly growing mycobacteria on the basis of its mycolic acid pattern and by a number of other phenotypic features, notably its ability to grow at higher temperatures. The type strain is Mycobacterium elephantis DSM 44368T. The EMBL accession number for the 16S rDNA sequence of strain 484T is AJ010747.

 1999. Equine Medicine and Surgery. Mosby, St. Louis MO USA.

Duvivier, D.H., Votion, D., Roberts, C.A., Art, T., Lekeux, P., 1999. Inhalation therapy of equine respiratory disorders. Equine Veterinary Education 11, 124-130.

Fowler, M.E., Miller, R.E., 1999. Zoo and Wild Animal Medicine Current Therapy 4. W.B. Saunders, Philadelphia.

Gaeth, A.P., Short, R.V., Renfree, M.B., 1999. The developing renal, reproductive, and respiratory systems of the African elephant suggest an aquatic ancestry. Proc Natl Acad Sci U S A 96, 5555-5558.
Abstract: The early embryology of the elephant has never been studied before. We have obtained a rare series of African elephant (Loxodonta africana) embryos and fetuses ranging in weight from 0.04 to 18.5 g, estimated gestational ages 58-166 days (duration of gestation is approximately 660 days). Nephrostomes, a feature of aquatic vertebrates, were found in the mesonephric kidneys at all stages of development whereas they have never been recorded in the mesonephric kidneys of other viviparous mammals. The trunk was well developed even in the earliest fetus. The testes were intra-abdominal, and there was no evidence of a gubernaculum, pampiniform plexus, processus vaginalis, or a scrotum, confirming that the elephant, like the dugong, is one of the few primary testicond mammals. The paleontological evidence suggests that the elephant's ancestors were aquatic, and recent immunological and molecular evidence shows an extremely close affinity between present-day elephants and the aquatic Sirenia (dugong and manatees). The evidence from our embryological study of the elephant also suggests that it evolved from an aquatic mammal.

Gage, L.J., Blasko, D.R., Galuppo, L.D. Diagnostics and treatment of severe swelling of the pharyngeal tissues of an African elephant (Loxodonta africana). Proceedings of the American Association of Zoo Veterinarians.  105-108. 1999. 10-9-1999.
Ref Type: Conference Proceeding

Brown, R.E., Butler, J.P., Godleski, J.J., Loring, S.H., 1997. The elephant's respiratory system: adaptations to gravitational stress. Respiratory Physiology 110, 67.
Abstract: Elephants have had to adapt to gravitational stresses imposed on their very large respiratory structures. We describe some unusual features of the elephant's respiratory system and speculate on their functional significance. A distensible network of collagen fibers fills the pleural space, loosely connects lung to chest wall but appears not to constrain lung-chest wall movements. Myriad spaces within the network and its rich supply of capillaries suggest effective local sources and sinks for pleural fluid that may replace the gravity-dependent flows of smaller mammals. The lung is partitioned into approximately equal to 1 cm3 parenchymal units by a system of thick, elastic septa that ramify throughout the lung from origins on the lung's elastic external capsule. Parenchymal units suspended upon the elastic septal system protect dependent alveoli from compression, thereby reducing the usual gravitational gradient of lung expansion. Intra-pulmonary airways are devoid of cartilage, instead they appear to derive resistance to collapse from tethering forces of the attached septa.

Osofsky, S.A., 1997. A practical anesthesia monitoring protocol for free-ranging adult African elephants (Loxodonta africana). Journal of Wildlife Diseases 33, 72-77.
Abstract: Twenty free-ranging adult African elephants in northern Botswana were immobilized with a mean (± SD) of 9.5 ± 0.5 mg etorphine hydrochloride and 2000 IU hyaluronidase by i.m. dart. The mean time to recumbency was 8.7 ± 2.4 min. All animals were maintained in lateral recumbency. The anaesthesia monitoring protocol included cardiothoracic auscultation; palpation of auricular pulse for quality and regularity; checking of rectal temperature, and monitoring of respiratory and heart rates. Results of basic physiological measurements were similar to those of previous field studies of African elephants immobilized with etorphine or etorphine-hyaluronidase. In addition, continuous real-time pulse rate and percent oxygen saturation of haemoglobin (SpO₂) readings were obtained on 16 elephants with a portable pulse oxygen meter. Duration of pulse oximetry monitoring ranged from 3 to 24 min (mean ±SD = 8.2 ± 4.8 min). Differences between minimum and maximum SpO₂ values for any given elephant ranged from 1 to 6 percentage points, evidence for relatively stable trends. The SpO₂ readings ranged from 70% to 96% among the 16 elephants, with a mean of 87.3 ± 2.8%. 15 of 16 elephants monitored with a pulse oximeter had mean SpO₂ values = 81 ± 2.4%, with 11 having mean SpO₂ values = 85 ± 1.5%. All 20 animals recovered uneventfully following reversal: diprenorphine at 23.3 ± 1.5 mg (IV) with 11.7 ± 0.5 mg IM, or 24 mg diprenorphine given all IV.

Dalovision, J.R., Montenegro-James, S., Kemmerly, S.A., Genre, C.F., Chambers, R., Pankey, G.A., Failla, D.M., Haydel, K.G., Hutchinson, L., Lindley, M.F., Praba, A., Eisenach, K.D., Cooper, E.S., 1996. Comparison of the amplified Mycobacterium tuberculosis (MTB) direct test, aplicor MTB PCR and IS6, 110-PCR for detection of MTB in respiratory specimens. Clin. Infect. Dis. 23, 1099-1106.

Lewandowski, K., Busch, T., Lewandowski, M., Keske, U., Gerlach, H., Falke, K.J., 1996. Evidence of nitric oxide in the exhaled gas of Asian elephants (Elephas maximus). Respiratory Physiology 106, 91-98.
Abstract: Nitric oxide (NO) produced in the respiratory tract is released into the respiratory gases of humans, rabbits, guinea-pigs, and rats. We analysed the NO concentrations in the exhaled gas of four awake Asian elephants. Two methods were employed: (1) exhaled gas was sampled from the elephants' trunks with a 1 L syringe and analysed for NO concentrations by chemiluminescence; (2) respiratory gas was continuously aspirated via a thin plastic tube positioned within the trunk and on-line analysed for NO concentrations by chemiluminescence. Syringe sampling (n = 4), when corrected for dilution by ambient air using linear regression analysis, revealed a mean NO concentration of 31 parts per billion (ppb); highest exhalatory concentrations measured during continuous suctioning were 27 and 28 ppb (n = 2). The exhaled NO concentrations in elephants are similar to those found in humans measured with a comparable technique. This supports the hypothesis that a size-independent 'normal value' of endogenous NO is provided in the airways which may contribute to regulation of pulmonary ventilation and perfusion by autoinhalation in some mammals.

Still, J., Raath, J.P., Matzner, L., 1996. Respiratory and circulatory parameters of African elephants (Loxodonta africana) anaesthetised with etorphine and azaperone. J S Afr Vet Assoc 67, 123-127.
Abstract: Department of Companion Animal Medicine and Surgery, Medical University of Southern Africa, Medunsa, South Africa.
Respiratory rate, heart rate, blood-gas tensions (PO2 and PCO2) and pH of arterial (a) and peripheral venous (v) blood, concentration of haemoglobin in arterial blood (Hb), saturation of arterial haemoglobin with oxygen and the end-expiratory concentration of oxygen were measured in 22 juvenile African elephants (Loxodonta africana) anaesthetised with etorphine and azaperone during a period of 35-65 minutes after they had assumed lateral recumbency. Based on these parameters the alveolar-arterial and arterial-peripheral venous differences of PO2 [P(A-a)O2 and P(a-v)O2 respectively] and oxygen content of arterial blood (CaO2) were calculated. Elephants with body mass of < or = 600 kg showed statistically significant changes in the following parameters, compared with elephants with a body mass of more than 600 kg (x +/- SD): PaO2 (64 +/- 11 versus 82 +/- 8 mmHg), P(a-v)O2 (9 +/- 5 versus 22 +/- 9 mmHg), P(A-a)O2(37 +/- 16 versus 15 +/- 8 mmHg) and Hb (148 +/- 20 versus 130 +/- 10 g/l) (p < 0.05). These findings suggested a tendency towards impaired oxygen exchange in the lungs, reduced peripheral extraction of oxygen and elevated oxygen-carrying capacity of arterial blood in smaller elephants. These changes were theoretically attributed to the respiratory-depressant and sympathomimetic effects of higher dosages of etorphine used in the smaller elephants to maintain a clinically acceptable anaesthetic plane. Individual elephants spent 35-150 minutes under anaesthesia and all recovered uneventfully after reversal of etorphine with diprenorphine.

Kramer, B., Hattingh, J., 1995. The neuromuscular junction in the African elephant Loxodonta africana and African buffalo Syncerus caffer. South African Journal of Wildlife Research 25, p14, 3p, 2bw.
Abstract: Differences in the physiological response to the drug succinyldicholine occur between the African elephant Loxodonta africana and African buffalo Syncerus caffer, irrespective of the route of administration of the drug. The response in elephants has suggested the presence of unique acetylcholine receptors in their respiratory muscles. In this paper the first observations of the neuromuscular junction in the African elephant and African buffalo are reported. While the basic structure of the junction was found to be typically mammalian in both species, differences were found in the morphology of the postjunctional area where these receptors reside. Elucidation of the structure and function of this junction in these animals is important in the selection of drugs that act as neuromuscular blockers.

Schumacher, J., Heard, D.J., Caligiuri, R., Norton, T., Jacobson, E.R., 1995. Comparative effects of etorphine and carfentanil on cardiopulmonary parameters in juvenile African elephants (Loxodonta africana).  Journal of Zoo and Wildlife Medicine 26, 503-507.
Abstract: Fourteen African elephants (Loxodonta africana) were immobilized with either etorphine hydrochloride (3.2 ± 0.5 µg/kg i.m.) or carfentanil citrate (2.4 µg/kg i.m.). Induction time with etorphine was significantly longer (30 ± 21 min) than with carfentanil (8 ± 2 min).  Immediately following immobilization all elephants were placed in lateral recumbency and respiratory rate, heart rate, and rectal body temperature were monitored every 5 min throughout the immobilization period.  Arterial blood samples, collected from an auricular artery, were taken 10 min after immobilization and every 15 min thereafter for up to 1 hr.  At the first sampling, mean values for arterial blood gas variables for etorphine immobilized elephants were pHa, 7.29 ± 0.03; PaCO₂, 53.4 ± 5.2 mmHg; PaO₂, 71.8 ± 13.8 mmHg; standard base excess (SBE), -1.6 ± 2.9 mEq/L; and HCO3, 25.7 ± 2.7 mEq/L. After 1 hr of immobilization, mean arterial blood gas values were pHa, 7.32 ± 0.06; PaCO₂ , 57.2 ± 9.6 mm Hg; and PaO₂ , 53.8 ± 10.5 mm Hg; SBE, 2.7 ± 1.4 mEq/L; and HCO_3-, 30.6 ± 1.6 mEq/L. For carfentanil immobilized elephants, blood gas values at the first time of collection were pHa, 7.28 ± 0.04; PaCO₂, 52.1 ± 2.8 mmHg; PaO₂, 78.3 ± 14.7 mmHg; SBE, -2.3 ± 24 mEq/L; and HCO_3-, 24.3 ± 2.1 mEq/L.  Sixty minutes after the first sampling, blood gas values of one elephant were pHa, 7.38; PaCO₂, 48.7 mmHg; PaO₂, 52 mmHg; SBE, 3.4 mEq/L, and HCO_3-, 28.8 mEq/L.  Over time there was a progressive decline in arterial PO2 in all elephants.  It is concluded that elephants immobilized with either etorphine HCl or carfentanil developed hypoxemia (PaO₂ < 60 mmHg) after 30 min of immobilization.  It is recommended that the administration of one of these opioid drugs be accompanied by supplemental oxygen, or followed by an inhalant anesthetic in 100% oxygen for prolonged procedures.  Diprenorphine or nalmefene reversal was rapid and uneventful in both the etorphine and carfentanil group.  No cases of renarcotization were noted. Additional excerpt: All elephants in the etorphine group (n=8) received diprenorphine at a mean dosage of 8.3 ± 1.1 µg/kg IV. Two elephants in the carfentanil group (n=6) were administered diprenorphine at a dosage of 8.9 µg/kg IV and IM.  Three elephants in this group received nalmefene hydrochloride.  One of the three elephants was given nalmefene 166.7 µg/kg both IV and SC. Two of the three elephants were given nalmefene IV and IM. The dosage was 88.9 µg/kg IV and IM in one elephant and 53.3 µg/kg IV and IM in the other. One elephant in the carfentanil group was administered nalmefene (88.9 µg/kg IV) followed by diprenorphine (8.9 µg/kg IM).

Honeyman, V.L., Pettifer, G.R., Dyson, D.H., 1992. Arterial blood pressure and blood gas values in normal standing and laterally recumbent African (Loxodonta africana) and Asian (Elephas maximus) elephants. Journal of Zoo and Wildlife Medicine 23, 205-210.
Abstract: Normal cardiopulmonary data in seven African (Loxodonta africana) and eight Asian (Elephas maximus) elephants were documented in conscious animals standing and in left lateral (LL) recumbency.  In the standing position, arterial blood pressures, heart and respiratory rates, and blood gas values did not differ (P > 0.05) over time or between species. Systolic, diastolic, and blood pressure means (+/- SEM) were 178.6 (+/- 2.94), 118.7 (+/- 3.10), and 144.6 (+/- 2.90) mm Hg, respectively, in unsedated standing elephants.  Arterial blood pressures increased (P </= 0.05) with time in LL recumbency and were highest (179.83 +/- 9.32) by the last reading at 16.5 +/- 0.41 min.  Arterial PO2 values decreased (P </= 0.05) from 96.2 (+/- 1.55) mm Hg while standing to 83.8 (+/- 3.37) mm Hg by 13.6 (+/- 6.8) min in LL recumbency.  Lateral recumbency increased (P < 0.05) arterial pH, adjusted base excess, and HCO3- content; however, these changes were not considered clinically significant.  Clinically healthy unsedated laterally recumbent elephants may be at risk of developing clinically significant hypoxemia and hypertension in the absence of alteration in more readily measured cardiopulmonary parameters.

Yathiraj, S., Choudhuri, P.C., Rao, D.S.T., Reddy, P.K., 1992. Clinico-haematological observations on Indian elephant (Elephas maximus indicus). Indian Veterinary Journal 69, 995-997.
Abstract: In 3 apparently healthy elephants (a male aged 40, and 2 females aged 20 and 60) the mean values for heart rate, respiratory rate and body temperature, respectively, were 34.66±1.08/min, 7.88±0.09/min and 35.25±0.07°C in the mornings, and 36.22±1.07/min, 8.33±0.15/min and 35.75±0.06°C in the afternoons. Haemoglobin values averaged 11.65±0.49 g%, and PCV 33.25±0.46%. Various erythrocyte and leukocyte counts and indices are presented.

Barile, M.F., Yoshida, H., Roth, H., 1991. Rheumatoid arthritis: New findings on the failure to isolate or detect mycoplasmas by multiple cultivation or serologic procedures and a review of the literature. Reviews of Infectious Diseases 13, 571-582.
Abstract: Using different and elaborate broth, agar, and cell culture procedures, we failed to isolate mycoplasmas, ureaplasmas, spiroplasmas, or chlamydiae from the synovial fluid of 10 patients with rheumatoid arthritis (RA) and from six patients with non-rheumatoid arthritis (NRA).  In addition, sera from 35 patients with NRA also were examined.  Although some of the sera had moderately high titers of metabolism-inhibiting antibody to some of the 10 human Mycoplasma species, especially to the common respiratory pathogen Mycoplasma pneumoniae, and to some of the eight Ureaplasma urealyticum serovars, especially serovars V and VII, there were no significant differences between titers of these antibodies in the two groups of patients.  Among RA patients serum antibody titers to M. pneumoniae were 1:32 in five and 1:16 in eight; two patients had higher synovial fluid titers (1:16) than serum titers (1:4).  The geometric mean titer (GMT) of antibody to serovar V in synovial fluid was higher in RA patients than in NRA patients, but the difference did not reach significance (P=.056).  Reports on the possible role of infectious agents in the pathogenesis of rheumatoid arthritis are reviewed.

Fowler, M.E. Tuberculosis in zoo ungulates. Essey, M. A. Bovine tuberculosis in cervidae: Proceedings of a symposium.  37-41. 1991. Washington,D.C., United States Department of Agriculture Miscellaneous Publication No. 1506.
Ref Type: Conference Proceeding

Gorina, L.G., Goncharova, S.A., Igumnov, A.V., 1991. Laboratory diagnosis of human mycoplasmoses. Vestnik Adademii Meditsinskikh Nauk SSSR 1991, 44-47.

Hattingh, J., Pitts, N.I., De-Vos, N.I., Moyes, D.G., Ganhao, M.F., 1991. The response of animals to suxamethonium (succinyldicholine) and succinylmonocholine. Journal of the South African Veterinary Association 62 , 126-129.
Abstract: The time which elapses before cessation of breathing, and blood pressure and blood gas changes after the i.m. administration of suxamethonium, or a mixture of suxamethonium and hexamethonium, was compared in immobilized African elephants (Loxodonta africana) and buffaloes (Synceros caffer). In addition, the respiratory responses of elephants and other animals to i.v. administration of suxamethonium and succinylmonocholine are reported, as are the effects of darting animals with succinylmonocholine. Respiration was affected in a similar fashion in all species investigated. However, the characteristic gradual decrease in respiratory rate seen in elephants during culling, using suxamethonium, resembles the effects observed when succinylmonocholine is administered. It is suggested that elephants are killed by this first breakdown product of suxamethonium during culling and/or that unique acetylcholine receptors may be involved.

Panicker, K.R., Valsala, K.V., 1990. Bronchopneumonia in an elephant. Indian Journal of Animal Health 29, 85.

Stephanos, J.J., Addison, A.W., 1990. Spectroscopic and kinetic aspects of Elephas maximus hemoglobin. Eur. J Biochem. 189, 185-191.
Abstract: In comparison with myoglobin and human and Glycera dibranchiata hemoglobins, the heme distal side amino acid exchanges within the heme environment of elephant tetrameric hemoglobin (Hbe) only slightly affect the electronic and ESR spectra of Hbe(III) and Hbe(II) derivatives, several of which were prepared and characterized by optical and ESR spectroscopy. Addition of 2,3- bisphosphoglycerate or inositol hexakisphosphate to Hbe(II)NO causes tension in the Fe-N(proximal His) bond, although the behaviour differs in detail from that of HbA(II)NO. There are two equilibrium states of Hbe having significantly different kinetics for the Hbe(III)----Hbe(II) reaction of Hbe(III)NO. This autoreduction occurs in the form of two parallel processes, which collapse into one intermediate rate in the presence of Gri(2, 3)P2. The temperature dependences of the rates enable deduction of delta H0 and delta S0 for the linked equilibrium, and yield linear Eyring plots for Hbe(III)NO, from which activation parameters were estimated on the basis of a previously described mechanism

Yu, L.P., La Mar, G.N., Mizukami, H., 1990. Rearrangement of the distal pocket accompanying E7 His----Gln substitution in elephant carbonmonoxy- and oxymyoglobin: ¹H NMR identification of a new aromatic residue in the heme pocket. Biochemistry 29, 2578-2585.
Abstract: Two-dimensional 1H NMR methods have been used to assign side- chain resonances for the residues in the distal heme pocket of elephant carbonmonoxymyoglobin (MbCO) and oxymyoglobin (MbO2). It is shown that, while the other residues in the heme pocket are minimally perturbed, the Phe CD4 residue in elephant MbCO and MbO2 resonates considerably upfield compared to the corresponding residue in sperm whale MbCO. The new NOE connectivities to Val E11 and heme-induced ring current calculations indicate that Phe CD4 has been inserted into the distal heme pocket by reorienting the aromatic side chain and moving the CD corner closer to the heme. The C zeta H proton of the Phe CD4 was found to move toward the iron of the heme by approximately 4 A relative to the position of sperm whale MbCO, requiring minimally a 3-A movement of the CD helical backbone. The significantly altered distal conformation in elephant myoglobin, rather than the single distal E7 substitution, forms a plausible basis for its altered functional properties of lower autoxidation rate, higher redox potential, and increased affinity for CO ligand. These results demonstrate that one-to-one interpretation of amino acid residue substitution (E7 His----Gln) is oversimplified and that conformational changes of substituted proteins which are not readily predicted have to be considered for interpretation of their functional properties

Heard, D.J., Kollias, G.V., Webb, A.I., Jacobson, E.R., Brock, K.A., 1988. Use of halothane to maintain anesthesia induced with etorphine in juvenile African elephants. Journal of the American Veterinary Medical Association 193, 254-256.
Abstract: Excerpts: Sixteen 3- to 5-year-old African elephants were anesthetized one or more times for a total of 27 diagnostic and surgical procedures.  Xylazine (0.1 ± 0.04 mg/kg of body weight, mean ± SD) and ketamine (0.6 ± 0.13 mg/kg) administered IM induced good chemical restraint in standing juvenile elephants during a 45-minute transport period before administration of general anesthesia.  After IM or IV administration of etorphine (1.9 ± 0.56 micrograms/kg), the mean time to lateral recumbency was 20 ± 6.6 and 3 ± 0.0 minutes, respectively.  The mean heart rate, systolic blood pressure, and respiration rate during all procedures was 50 ± 12 beats/min, 106 ± 19 mm of Hg, and 10 ± 3 breaths/min, respectively. Cardiac arrhythmias were detected during 2 procedures.  In one elephant paroxysmal ventricular tachycardia was detected and the procedure terminated when the arrhythmia failed to stabilize after multiple doses of lidocaine (1 mg/kg, IV).  In another elephant, second degree atrioventricular block returned to normal sinus rhythm after IV administration of atropine (0.04 mg/kg). In one elephant, low mean blood pressure (54 mm of Hg) responded to reduction in halothane (vaporizer setting 1 to 0.75%) and slow infusion of dobutamine HCl ((250 mg/1,000 ml) given to effect. The systolic blood pressure increased to 90 mm of Hg and remained high with a continuous infusion of dobutamine (5 µg/kg/min). Immediately after induction in another elephant, profound respiratory depression (< 1 breath / minute) and palpably weak arterial pulse were identified.  Intravenous administration of diprenorphine at half the recommended reversal dose resulted in improvement of respiration and palpable arterial pulse, without the elephant developing signs of complete anesthetic reversal. Alterations in systolic blood pressure, ear flapping, and trunk muscle tone were useful for monitoring depth of anesthesia.  Results indicated that halothane in oxygen was effective for maintenance of surgical anesthesia in juvenile African elephants after induction with etorphine.  Note: A correction appeared in a later volume 193(6): p.721.

Thoen, C.O., 1988. Tuberculosis. Journal of the American Veterinary Medical Association 193, 1045-1048.

Fischer, M.S., 1987. The trunk of elephants. Zeitschrift fur Saugetierkunde 52, 262-263.

Sharma, V.S., Traylor, T.G., Gardiner, R., Mizukami, H., 1987. Reaction of nitric oxide with heme proteins and model compounds of hemoglobin. Biochemistry 26, 3837-3843.
Abstract: Rates for the reaction of nitric oxide with several ferric heme proteins and model compounds have been measured. The NO combination rates are markedly affected by the presence or absence of distal histidine. Elephant myoglobin in which the E7 distal histidine has been replaced by glutamine reacts with NO 500-1000 times faster than do the native hemoglobins or myoglobins. By contrast, there is no difference in the CO combination rate constants of sperm whale and elephant myoglobins. Studies on ferric model compounds for the R and T states of hemoglobin indicate that their NO combination rate constants are similar to those observed for the combination of CO with the corresponding ferro derivatives. The last observation suggests that the presence of an axial water molecule at the ligand binding site of ferric hemoglobin A prevents it from exhibiting significant cooperativity in its reactions with NO.

Johnson, B., Burton, M., Qualls, C.W., Jr., 1986. Interstitial pulmonary fibrosis in an African elephant. Journal of the American Veterinary Medical Association 189, 1188-1190.

Jongeward, K.A., Marsters, J.C., Mitchell, M.J., Magde, D., Sharma, V.S., 1986. Picosecond geminate recombination of nitrosylmyoglobins. Biochem. Biophys. Res. Commun. 140, 962-966.
Abstract: The kinetics of NO geminate recombination to sperm whale and elephant myoglobins has been studied on the picosecond time scale using an amplified colliding-pulse mode-locked ring dye laser. The dynamics of ligand rebinding are shown to be affected by the distal structure of the protein surrounding the heme pocket.

Mizukami, H., Bartnicki, D.E., 1986. Unusual myoglobin of elephant. Elephant 2, 80-81.
Abstract: Myoglobins are proteins found in muscle fibers and they store and carry oxygen.  They also bind carbon monoxide (CO).  Myoglobins of Loxodonta africana  and Elephas maximus are different from myoglobins of most other animals.  Most significantly, elephant myoglobins react with CO nearly eight times more strongly than other myoglobins.  This means that elephants housed close to expressways (where emission of CO from motor vehicles is greatest) would be affected by the toxic gas more than other animals would.  On the other hand, elephant myoglobin resists oxidation to a greater extent and, thus, is more stable to the actions of certain toxins.

Yu, N.T., Thompson, H.M., Mizukami, H., Gersonde, K., 1986. The cobalt-nitrosyl stretching vibration as a sensitive resonance Raman probe for distal histidine-nitrosyl interaction in monomeric hemoglobins. Eur. J Biochem. 159, 129-132.
Abstract: The Co-NO stretching vibration has been assigned in the resonance Raman spectra of various cobalt-substituted monomeric hemoglobins by employing isotope-labeling of nitrosyl (14N16O, 15N16O, 14N18O). Monomeric hemoglobins with a distal histidine (sperm whale myoglobin and leghemoglobin) exhibit this vibration at 573-575 cm-1, whereas hemoglobins without distal histidine (elephant myoglobin and insect hemoglobin from Chironomus thummi thummi, CTT III) show this vibration in the range of 553-558 cm- 1. The Fe-NO stretching vibration which occurs in the range of 554-556 cm-1 does not reflect the distal histidine-ligand interaction. Therefore, the Co-NO moiety which is isoelectronic with the Fe-O2 moiety is a good monitor for distal effects on the exogenous ligand of hemoglobins, especially due to the fact that in hemoglobins with distal histidine the Fe-O2 stretching vibration (567-572 cm-1) is similar to the Co-NO stretching vibration

Kerr, E.A., Yu, N.T., Bartnicki, D.E., Mizukami, H., 1985. Resonance raman studies of CO and O₂ binding to elephant myoglobin (distal His(E7)----Gln). Journal of Biological Chemistry 260, 8360-8365.
Abstract: Carbon monoxide and dioxygen were employed as resonance Raman- visible ligands for probing the nature of the heme-binding site in elephant myoglobin, which has glutamine in the distal position (E7) instead of the usual histidine. The distal histidine (E7) residue has been thought to be responsible for weakening carbon monoxide binding to hemoproteins. It is of interest to see how the His(E7)----Gln replacement affects such parameters as nu(Fe-N epsilon), nu(Fe-CO), delta(Fe-C-O), nu(C-O), delta(Fe-O-O), and nu(O-O) vibrational frequencies and relative intensities. Elephant myoglobin has a CO affinity approximately 6 times higher than that for human/sperm whale myoglobin (Mb). If this enhanced affinity were solely due to the removal of some of the steric hindrance that normally tilts the CO off the heme axis, one would expect the nu(Fe-CO) frequency to decrease and the nu(C-O) frequency to increase relative to the corresponding values in sperm whale Mb. However, the opposite was found. In addition, strong enhancement of the Fe-C-O bending mode was observed. These results suggest that the Fe-C-O linkage remains distorted. In elephant Mb, new interactions resulting from the conformational change accompanying ligand binding may be responsible for the increased CO binding. Similar spectra were obtained for elephant and sperm whale oxymyoglobin. This suggests that the interactions of bound O2 are not markedly affected by the glutamine replacement

Wemmer, C., Mishra, H., Dinerstein, E., 1985. Unusual use of the trunk for sound production in a captive Asian elephant: a second case. Journal of the Bombay Natural History Society 82, 187.

Braunitzer, G., Stangl, A., Schrank, B., Krombach, C., Weisner, H., 1984. Phosphate-haemoglobin interaction. The primary structure of the haemoglobin of the African elephant (Loxodonta africana, Proboscidea): asparagine in position 2 of the beta-chain. Hoppe-Seyler's Z. Physiol. Chem. 365, 743-749.
Abstract: The primary structure of the haemoglobin of the African Elephant (Loxodonta africana) is reported.  The sequence was determined by means of a sequenator.  The haemoglobin differs in 26 amino acids in the alpha-chains in and 27 in the beta-chains from that of adult human hemoglobin.  The haemoglobin of the African Elephant, like that of the Indian Elephant and the llama, has only 5 binding sites for polyphosphate.  This finding explains the low p(O₂)₅₀ value in whole blood as a result of the lower 2,3-bisphosphoglycerate-haemoglobin interaction.  This is discussed in relation to aspects of respiratory physiology; some points are also of interest with regard to the Second Punic War and Hannibal's crossing of the Alps.

Krishnamoorthi, R., La Mar, G.N., 1984. Identification of the titrating group in the heme cavity of myoglobin. Evidence for the heme-protein pi-pi interaction. Eur. J Biochem. 138, 135-140.
Abstract: The pH dependence of the proton NMR chemical shifts of met-cyano and deoxy forms of native and reconstituted myoglobins reflects a structural transition in the heme pocket modulated by a single proton with pK 5.1-5.6. Comparison of this pH dependence of sperm whale and elephant myoglobin and that of the former protein reconstituted with esterified hemin eliminates both the distal histidine as well as the heme propionates as the titrating residue. Reconstitution of sperm whale met-cyano myoglobin with hemin modified at the 2,4-positions leads to a systematic variation in the pK for the structural transition, thus indicating the presence of a coupling between the titrating group and the heme pi system. The results are consistent with histidine FG3 (His-FG3) being the titrating group, and a donor-acceptor pi- pi interaction between its imidazole and the heme is proposed.

Krishnamoorthi, R., La Mar, G.N., Mizukami, H., Romero, A., 1984. A proton NMR investigation of the influence of distal glutamine on structural and dynamic properties of elephant metmyoglobin. Journal of Biological Chemistry 259, 265-270.
Abstract: The proton NMR spectra of metmyoglobin from the Asian elephant, which has the replacement of glutamine for the usual distal histidine, are reported and analyzed. In the low pH region, we detect two interconvertible forms of the met-aquo-protein whose relative stabilities are independent of pH, but depend strongly on both temperature and solvent isotope composition. As the pH is raised, both species convert to the met-hydroxy form, as found for other myoglobins. The temperature dependence of the heme methyl shifts for both acidic protein forms indicates essentially high spin character for the iron, and the mean heme methyl shifts are interpreted as indicating one form with a very slightly weaker, and the other with a significantly stronger, axial ligand field than for the unique sperm whale met-aquo-myoglobin. The thermodynamic data for the equilibrium between the two species are consistent with differences of one hydrogen bond between coordinated water and the distal glutamine. Models are proposed where one form of the protein has not only the glutamine carboxyl oxygen acting as a hydrogen-bond acceptor, but also the amine group. We conclude that a distal glutamine can act both as a stronger and as a weaker hydrogen-bond acceptor towards coordinated water than the usual distal histidine. The relative rates of conversion of the two met-aquo-myoglobin forms to MetMbOH is found to be consistent with the proposed structures for the two forms.

Krishnamoorthi, R., La Mar, G.N., Mizukami, H., Romero, A., 1984. A ¹H NMR comparison of the met-cyano complexes of elephant and sperm whale myoglobin. Assignment of labile proton resonances in the heme cavity and determination of the distal glutamine orientation from relaxation data. Journal of Biological Chemistry 259, 8826-8831.
Abstract: The met-cyano complex of elephant myoglobin has been investigated by high field 1H NMR spectroscopy, with special emphasis on the use of exchangeable proton resonances in the heme cavity to obtain structural information on the distal glutamine. Analysis of the distance dependence of relaxation rates and the exchange behavior of the four hyperfine shifted labile proton resonances has led to the assignment of the proximal His-F8 ring and peptide NHs and the His-FG3 ring NH and the distal Gln-E7 amide NH. The similar hyperfine shift patterns for both the apparent heme resonances as well as the labile proton peaks of conserved resonances in elephant and sperm whale met-cyano myoglobins support very similar electronic/molecular structures for their heme cavities. The essentially identical dipolar shifts and dipolar relaxation times for the distal Gln-E7 side chain NH and the distal His-E7 ring NH in sperm whale myoglobin indicate that those labile protons occupy the same geometrical position relative to the iron and heme plane. This geometry is consistent with the distal residue hydrogen bonding to the coordinated ligand. The similar rates and identical mechanisms of exchange with bulk water of the labile protons for the three conserved residues in the elephant and sperm whale heme cavity indicate that the dynamic stability of the proximal side of the heme pocket is unaltered upon the substitution (His----Gln). The much slower exchange rate (by greater than 10(4] of the distal NH in elephant relative to sperm whale myoglobin supports the assignment of the resonance to the intrinsically less labile amide side chain

Poupa, O., Brix, O., 1984. Cardiac beat frequency and oxygen supply: a comparative study. Comp Biochem Physiol A 78, 1-3.
Abstract: The length of diastole in mammals varies between approx 1 s (elephant) and 38 ms (shrew) which makes oxygen supply in high speed cardiac pumps in very small mammals precarious. High capillary density and high blood P50 are reported in mammals with high frequency cardiac cycle. Both are probably insufficient when cardiac frequency is exceedingly high (shrew: 1000 min-1). High respiratory efficiency due to large relative mitochondrial volume per cell (greater than 50%) seems to be preferential solution to maintain sufficient O2-gradient. Similar strategy, i.e. high relative cardiac mitochondrial volume was reported in analogous situation in ice-fish (Chaenocephalus aceratus) where O2 cardiac cell supply is difficult due to the absence of hemoglobin and cardiac myoglobin.

Snider, D.E., Jr., Jones, W.D., Good, R.C., 1984. The usefulness of phage typing Mycobacterium tuberculosis isolates. Am. Rev. Respir. Dis. 130, 1095-1099.
Abstract: Mycobacteriophage typing of Mycobacterium tuberculosis isolates was used as an epidemiologic aid in investigating the transmission of tuberculosis in community, industrial, and institutional outbreaks. The technique was also useful in other situations, e.g., documenting congenital transmission of infection and distinguishing exogenous reinfection from endogenous reactivation. Additional studies are indicated to further explore the value of phage typing for tracking the transmission of tuberculosis in the community

Bartnicki, D.E., Mizukami, H., Romero-Herrera, A.E., 1983. Interaction of ligands with the distal glutamine in elephant myoglobin. Journal of Biological Chemistry 258, 1599-1602.
Abstract: The effects of distal glutamine (E7) replacement in elephant myoglobin were studied by comparing the temperature-dependent nitrosyl electron spin resonance spectra, redox potentials, and the acid-alkaline equilibria of elephant and human myoglobins. For myoglobins containing a distal histidine, the nitrosyl ESR spectra do not exhibit superhyperfine splitting until near liquid helium temperatures (Yoshimura, T., Ozaki, T., Shintani, Y., and Watanabe, H. (1979) Arch. Biochem. Biophys. 193, 301-313). Studies presented here show that the ESR spectra of nitrosyl elephant myoglobin exhibit 9-line superhyperfine splitting well above liquid nitrogen temperatures, similar to the temperature profiles of isolated heme complexes (Morse, R.H. (1980) Fed. Proc. 39, 2006). It is concluded that the shift in the spectral equilibrium to higher temperature indicates a diminished interaction between NO and the distal position in elephant myoglobin. In addition, the redox potential of elephant myoglobin was found to be nearly 100 mV greater than that of human myoglobin, and the pKa of the acid-alkaline equilibrium (oxidized myoglobin) was 8.5, being 0.4 unit less than that of other vertebrate myoglobins. These different reactivities between elephant and human myoglobins are discussed based on the nature of charge interactions between polar ligands and distal glutamine and histidine

Saunders, G., 1983. Pulmonary Mycobacterium tuberculosis infection in a circus elephant. Journal of the American Veterinary Medical Association 183, 1311-1312.

Braunitzer, G., Jelkmann, W., Stangl, A., Schrank, B., Krombach, C., 1982. Hemaglobins, XLVIII: the primary structure of hemoglobin of the Indian elephant (Elephas maximus, Proboscidae): beta 2 = Asn. Hoppe. Seylers. Z. Physiol. Chem. 363, 683-691.
Abstract: The primary structure of the hemoglobin of the Indian Elephant (Elephas maximus) is given. The sequence was determined automatically in a sequenator. By homologous comparison with adult human HbA, the alpha-chains differ by 24 exchanges and the beta-chains by 27 exchanges. Furthermore, we report p(O2)50 values with regard to altered contact sites with 2,3- bisphosphoglycerate in Indian elephant hemoglobin. Our findings explain the low p(O2)50 and the reduced interaction with 2,3- bisphosphoglycerate. Elephant hemoglobin has, like that of the Llama, only five phosphate binding sites. In addition, we have made an attempt to relate these results to aspects of respiratory physiology. Some implications of these biochemical and physiological results, concerning the Second Punic War and Hannibal's Alp transition, are given.

Jones, W.D., Jr., Good, R.C., 1982. Hazel elephant redux (letter). Am. Rev. Respir. Dis. 125, 270.
Abstract: Full text.  A recent letter from Greenberg, Jung and Gutter reported the untimely death of Hazel Elephant with Mycobacterium tuberculosis infection.  The authors concluded that the animal trainer, who was found to have cavitary tuberculosis, was probably the source of infection.  The conclusion was based on data available at the time.  The isolates from Hazel Elephant and the animal trainer were submitted to us for further study the state health departments of Louisiana and Florida.  Using the methodology and classification scheme previously described, we found that the cultures were of different phage types.  The isolate from the elephant was type A₀ (7), and the isolate from the trainer was type A₁ (7,13,14).  The isolates differed by lysis with one major phage (MTPH 5) and two auxiliary phages (MTPH 13 and 14). We have previously used phage typing of M. tuberculosis in several well-defined outbreaks as an adjunct to other epidemiologic procedures.  The isolates were typed without the laboratory's knowing epidemiologic relationships between cases.  The results indicated that M. tuberculosis transmitted from one individual to another retained the same phage-type characteristics.  In the present study, our phage-type results suggest that the animal trainer and the elephant were infected from two different sources and that occurrence of disease in the animal and the trainer was coincidental.  We are still evaluating page typing as a procedure for use in tuberculosis epidemiology and can accept selected cultures for phage typing in special situations if we are contacted before the cultures are submitted.

Greenberg, H.B., Jung, R.C., Gutter, A.E., 1981. Hazel Elephant is dead (of tuberculosis) (letter). Am. Rev. Respir. Dis. 124, 341.
Abstract: Full text.  Hazel Elephant was only 35 years old (by our estimate) when she died.  She was cooperative and trusting to the last.  Had we known about her illness sooner, we could have saved her.  The  Mycobacterium tuberculosis, var hominis  that killed Hazel was sensitive to our drugs at the following levels: INH to 0.2mcg/ml; PAS to 2 mcg/ml; R to 1 mcg/ml; and MAB to 5 mcg/ml.  Hazel worked and performed for a travelling circus. Ordinarily good-humored and loving, she had been off her feed for weeks.  She became listless and apathetic, her eyes lost their sparkle, and she lacked her customary elan.  Nonetheless, Hazel continued to perform for the children and do her other chores until she came to New Orleans.  When Hazel got to New Orleans, she could barely move.  The circus's bosses called for help.  The brought her to the hospital at the Audubon Park and Zoological Garden.  As soon as we saw Hazel, we admitted her to the isolation ward.  We have her fluids, electrolytes, and antibiotics.  We got cultures and other clinical laboratory tests.  We comforted Hazel and tried to put her at ease.  It was too late.  She fell to the ground, her rheumy eyes gazed at us pitifully, her respirations failed, and she died.  Hazel's postmortem examination took six hours.  She was an emaciated Asian elephant whose lungs were filled with caseating granulomata.  Since microscopy showed myriads of acid-fast bacilli, we examined everyone who had, or who thought they had, contact with Hazel.  We found three persons with positive tuberculin skin test results.  None had tuberculous disease. Fortunately, Hazel had been kept away from other animals. Hazel's circus did not wait for the results of our autopsy.  It left Louisiana.  The U.S. Public Health Service tracked it down and found the man, an animal trainer with cavitary tuberculosis, who probably gave Hazel her fatal disease.  Now another health department will have to deal with the circus and its animals.

Gutter, A. Mycobacterium tuberculosis in an Asian elephant. Proc.Am.Assoc.Zoo Vet.  105-106. 1981.
Ref Type: Conference Proceeding

McGavin, M.D., Schroeder, E.C., Walker, R.D., McCracken, M.D., 1981. Fatal aspiration pneumonia in an African elephant. Journal of the American Veterinary Medical Association 179, 1249-1250.

Paladino, F.V., Spotila, J.R., Pendergast, D. Respiratory variables of Indian and African elephants. American Zoologist 21[4], 1043. 1981.
Ref Type: Abstract
Abstract: Full Text.  End expiratory gas samples of Indian and African Elephants were analyzed for O₂ and CO₂.  At rest the mean measured O₂ deficit for Adult Indian Elephants was 3.0% O₂ with a CO₂ increment of 3.18% CO₂ (R.Q.=1.06). Immediately after 10 minutes of exercise the 3 adult Indian Elephants had a mean 4.75% O₂ deficit and 5.2% CO₂ increment (R.Q.=1.1).  One juvenile Indian Elephant had a resting O₂ deficit of 4.12% and a 4.6% CO₂ increment (R.Q.=1.12) indicating a slightly higher metabolic rate.  One adult African Elephant had a resting 4.2% O₂ deficit and a 4.33% CO₂ increment (R.Q.=1.03).

Romero-Herrera, A.E., Goodman, M., Dene, H., Bartnicki, D.E., Mizukami, H., 1981. An exceptional amino acid replacement on the distal side of the iron atom in proboscidean myoglobin. Journal of Molecular Evolution 17, 140-147.
Abstract: Amino acid sequence determination of elephant myoglobin revealed the presence of the unusual substitution E7 His -- Gln.  Stereochemical analyses suggest that the most suitable residue which can functional substitute for His at this position in vertebrate globins in Gln.  Physiological studies imply that the slower rate of autooxidation of elephant is the result of this substitution which may confer some selective advantage on the species.  Comparative sequence data of paenungulate myoglobins suggest that the His -- Gln mutation probably occurred in an ancestor of Elephantinae.

Thoen, C.O., Himes, E.M., 1980. Mycobacterial infections in exotic animals. In: Montali, R.J., Migaki, G. (Eds.), The comparative pathology of zoo animals. Smithsonian Institution Press, Washington,D.C., pp. 241-245.
Abstract:  Mycobacteria were isolated from 59% of the 826 specimens submitted from exotic animals suspected of having tuberculosis.  Mycobacterium bovis and Mycobacterium tuberculosis accounted for 61% of the isolations from nonhuman primates.  Mycobacterium bovis was the organism most frequently isolated from hoofed animals and Mycobacterium avium was most commonly isolated from birds.  The distribution, pathogenesis, diagnosis, and control of tuberculosis in exotic animals is discussed.

Bartels, H., 1976. Comparative aspects of respiration and circulation in mammals. Pneumonologie Supplement 1-9.

Alford, B.T., Burkhart, R.L., Johnson, W.P., 1974. Etorphine and diprenorphine as immobilizing and reversing agents in captive and free-ranging mammals. Journal of the American Veterinary Medical Association 164, 702-705.
Abstract: Summary:  Etorphine, an opium alkaloid derivative of thebaine, and its specific antagonist, diprenorphine, were evaluated by research workers and zoo veterinarians in captive and free-ranging animals.    An intramuscular injection of etorphine usually resulted in rapid immobilization, sedation, analgesia, and muscle relaxation in Equidae, Ursidae, Cervidae and Bovidae, when given at a rate of 0.44, 0.5, 0.98 and 1.09 mg/45 kg (100 lb.), respectively. Satisfactory immobilization was usually achieved within 5 to 15 minutes after intravenous administration of diprenorphine at twice the etorphine dosage.    Procedures performed after etorphine administration included dehorning, blood sampling, tail docking, antibacterial injection, radiography, orthopedic surgery, and obstetrical manipulation.    Side effects were commonly noticed in free-ranging mammals. The type and degree of reaction varied according to the species and included tachycardia, bellowing, bradycardia, respiratory depression, opisthotonos, muscular tremors, mydriasis, and hyperpyrexia.  Of 1,600 animals tested, 2.9% died as a result of severe heat prostration, inhalation pneumonia, respiratory depression, severe excitement due to underdosing, cardiac arrest, and inapparent disease.

Fowler, M.E., Hart, R., 1973. Castration of an Asian elephant, using etorphine anesthesia. Journal of the American Veterinary Medical Association 163, 539-543.
Abstract: A 9-year-old Asian elephant was castrated, using etorphine HCl for anesthesia.  The intraabdominal surgery was completed in 2 stages.  Respiratory and heart rates were normal throughout each surgical procedure.  Normal PaCO₂ and PaO₂ were maintained without the need of intermittent positive pressure ventilation.

Dhindsa, D.S., Sedgwick, C.J., Metcalfe, J., 1972. Comparative studies of the respiratory functions of mammalian blood.  VIII. Asian elephant (Elephas maximus) and African elephant (Loxodonta africana africana). Respiratory Physiology 14, 332-342.
Abstract: Respiratory characteristics of blood from four Asian and three African elephants were studied.  Oxygen dissociation curves of whole blood were constructed at 37 C and corrected to a plasma pH of 7.40.  The mean blood P50 values were 25.2 ± 0.5 and 23.2 ± 1.3 mm for Asian and African elephants, respectively, and these values are significantly different (p< 0.01).  The Bohr factors for both species were similar and averaged -0.351 ± 0.029 log PO2/ pH.  The Haldane effect was similar in both species (5.5 vol% C CO2 at PCO2 = 40 mmHg). The concentration of 2,3-diphosphoglycerate in elephant blood is similar to that found in normal human blood.  The blood morphology of both species was similar except that the leukocyte count was significantly higher in Asian elephants.  Starch gel electrophoresis showed that hemoglobin of Asian elephants travels at a slower rate than hemoglobin of African elephants, but both migrate faster than human A hemoglobin.

McCully, R.M., Basson, P.A., Pienaar, J.G., Erasmus, B.J., Young, E., 1971. Herpes nodules in the lung of the African elephant [Loxodonta africana (Blumenbach, 1797)]. Onderstepoort Journal of Veterinary Research 38, 225-236.
Abstract: Lymphoid nodules associated with Cowdry Type A intranuclear inclusions in epithelial and syncytial cells were found in the lungs of 74% of 50 African elephants in the Kruger National Park.  Subsequent studies proved these were caused by a herpes virus (Erasmus,McCully,Pienaar,Young, Pieterse & Els, 1971).  The disease appears to be subclinical or latent.  This virus, in common with other herpes viruses, might be more pathogenic in some other host.  The pathogenesis of the lymphoid nodules and the various stages of their formation are given and the detailed characteristics are illustrated.

Gorovitz, C., 1969. Tuberculosis in an African elephant. American Association of Zoo Veterinarians Newsletter January 20.

Riegel, K., Bantels, H., Buss, I.O., Wright, P.G., Kleihauer, E., Luck, C.P., Parer, J.T., Metcalfe, J., 1967. Comparative studies of respiratory functions of mammalian blood. IV. Fetal and adult African elephant blood. Respiratory Physiology 2, 182.

Seneviratna, P., Wettimuny, S.G., Seneviratna, D., 1966. Fatal tuberculosis pneumonia in an elephant. Veterinary Medicine Small Animal Clinician 60, 129-132.
Abstract: A fatal case of tuberculosis pneumonia with anemia and helminthiasis in a Ceylon elephant is reported. Acid-fast organisms resembling Mycobacterium tuberculosis  and tubercular nodules were seen in large numbers in sections of the lung.

Buettner-Janusch, J., Buettner-Janusch, V., Sale, J.B., 1964. Plasma proteins and haemoglobins of the African elephant and the hyrax. Nature 201, 510-511.

Bartels, H., Hilpert, P., Barbey, K., Betke, K., Riegel, K., Lang, E.M., Metcalfe, J., 1963. Respiratory functions of blood of the yak, llama, camel, Dybowski deer and African elephant. American Journal of Physiology 205, 331-336.
Abstract: Blood samples from a yak, llama, camel, deer, and African elephant were analyzed for oxygen capacity, "standard bicarbonate" content, oxygen dissociation curve, and the magnitude of the Bohr and Haldane effects.  These parameters of the respiratory function of the blood have been related to the morphology of the red cells, to the weights of the animals, and to the important electrolytes in the erythrocytes and in the plasma.  The high affinity for oxgen described previously for llama blood is shared by its relative, the camel.  Both of these animals have a high concentration of hemoglobin within their erythrocytes.  Blood from the African elephant showed the greatest affinity for oxygen among the subjects studied.

Engel, S., 1963. The respiratory tissue of the elephant (Elephas indicus), second communication. Acta Anatomica Nipponica 55, 105-111.
Abstract: The acini of the elephant lung are small but extremely numerous, thus providing an extensive respiratory surface.  The parenchyma is subdivided by elastic strands encapsulating small areas of parenchyma.  Many, especially peripheral, acini have a lymph system of their own, conspicuously marked by round, peduncular lymph nodes. Generally speaking, the Elephant lung is built up according to the usual pattern of the mammalian lung but contains peculiar structures necessary for the bulk of the body and the volume of the lung.

Riggs, A., 1963. The amino acid composition of some mammalian hemoglobins: mouse, guinea pig and elephant. Journal of Biological Chemistry 238, 2983-2987.

Evans, G.H., 1961. Elephants and Their Diseases: A Treatise on Elephants. Government Printing, Rangoon, Burma.

Halloran, P.O., 1955. A bibliography of references to diseases in wild mammals and birds. American Journal of Veterinary Research 16(part 2), 161.

Engel, S., 1952. The respiratory tissue of the elephant (Elephas indicus). Acta Anatomica Nipponica 16 , 308-314.

Eales, N., 1929. The anatomy of a foetal African elephant, Elephas africanas (Loxodonta africana). Part III.  The contents of the thorax and abdomen, and the skeleton. Transactions of the Royal Society of Edinburgh 56, part I, 203-246.

Todd, T.W., 1913. Notes on the respiratory system of the elephant. Anatomischer Anzeiger 44, 175-183.

Evans, G.H., 1910. Elephants and Their Diseases: A Treatise on Elephants. Government Printing, Rangoon, Burma.

Miall, L.C., Greenwood, F., 1879. The anatomy of the Indian elephant. Part III alimentary canal and its appendages. Journal of Anatomy and Physiology 13, 17-50.

Watson, M., 1872. Contributions to the anatomy of the Indian elephant. Part I. The thoracic visera. Journal of Anatomy and Physiology 6, 82-94.

Harrison, R., 1850. On the larynx, trachea, and oesophagus of the elephant. Proceedings of the Royal Irish Academy 4, 132-135.

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