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R Isaza

Publications and source records attributed to R Isaza.

At least 19 recordsLinked to original sources
PubMed2005

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana).

We recently described the clinical presentation and treatment of 18 elephants from six herds infected with TB. Treatment protocols and methods varied between herds to include both oral and rectal dosing using multiple drug doses and formulations. In this paper we present information regarding the pharmacokinetics (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial treatment regimens. Forty-one elephants received INH daily by either oral or rectal administration with different formulations. Population PK analysis was performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral administration indicated that compared with premixed INH solution, the drug exposure was highest with a suspension prepared freshly with INH powder. When INH was concomitantly given as an admixture over food, Tmax was delayed and variability in drug absorption was significantly increased. Compared with oral administration, similar drug exposures were found when INH was dosed rectally. The data generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate for initial TB treatment in elephants when premixed solution is administered directly into the oropharynx or rectal vault and 4 mg/kg are when INH is administered following immediate suspension from powdered form.

Administration, Oral↗
PubMed2005

Population pharmacokinetics of pyrazinamide in elephants.

This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T(max) at or before 2 h regardless of the method of drug administration. C(max) at a mean dose of 25.6 (+/-4.6) mg/kg was 19.6 (+/-9.5 microg/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C(max) was 25% (4.87 +/- 4.89 microg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded C(max) of 12.3 +/- 6.3 microg/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C(max) and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved C(max) values are below the recommended 20-50 microg/mL range.

Administration, Oral↗
PubMed2005

Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus).

Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.

Animals↗
PubMed2004

Simultaneous extraction and quantitation of fentanyl and norfentanyl from primate plasma with LC/MS detection.

The quantitation of both fentanyl and its desalkyl metabolite, norfentanyl, in plasma using LC/MS has not been previously described. The detection and quantitation of fentanyl and norfentanyl was achieved using LC/MS detection. The liquid-liquid extraction used toluene as the organic phase. Chromatography was carried out using a Zirchrom-PBD (50 mm x 2.1 mm, 3 microm) column with a mobile phase of acetonitrile-ammonium acetate (10 mM), citrate (0.1 mM, pH 4.4) (45:55, v/v) with a flow rate of 0.3 ml/min. Mass spectroscopy detection was performed using ESI in the positive mode. The LOQ for fentanyl was 25 pg/ml and norfentanyl was 50 pg/ml. For the concentrations of 75, 250, and 750 pg/ml, respectively, fentanyl had inter-day precisions of 6.6, 7.2, and 6.6% with accuracies of 4.0, 5.1, and 5.1% and intra-day precisions of 1.6, 1.9, and 1.9% with accuracies of 11.6, 9.4, and 8.4%, and norfentanyl had inter-day precisions of 7.4, 0.3, and 0.7% with accuracies of 9.1, 8.8, and 12.3% and intra-day precisions of 5.3, 1.4, and 0.1% with accuracies of 10.9, 8.9, and 12.8%. The recoveries of fentanyl were 85, 92, and 75% and of norfentanyl were 40, 49, and 46% at the 75, 250, and 750 pg/ml concentrations, respectively.

Animals↗
PubMed2003

Azithromycin metabolite identification in plasma, bile, and tissues of the ball python (Python regius).

Azithromycin is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin and to determine, if possible, the structure and number of circulating azithromycin metabolites. After a 4-month wash-out period, the snakes were given azithromycin p.o. as a single dose of 10 mg/kg for the study of azithromycin metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin accounted for 70% of total azithromycin- associated material in bile. In liver and kidney, unchanged azithromycin accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin are unique to this species. Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin in bile is not different between the three species.

Administration, Oral↗
PubMed2001

Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian elephants (Elephas maximus).

The deaths of two Asian elephants (Elephas maximus) in August 1996 led the United States Department of Agriculture to require the testing and treatment of elephants for tuberculosis. From August 1996 to September 1999. Mycobacterium tuberculosis infection was confirmed by culture in 12 of 118 elephants in six herds. Eight diagnoses were made antemortem on the basis of isolation of M. tuberculosis by culture of trunk wash samples; the remainder (including the initial two) were diagnosed postmortem. We present the case histories, epidemiologic characteristics, diagnostic test results, and therapeutic plans from these six herds. The intradermal tuberculin test, enzyme-linked immunosorbent assay serology, the blood tuberculosis test, and nucleic acid amplification and culture are compared as methods to diagnose M. tuberculosis infection in elephants.

Animals↗
PubMed2001

Persistent right aortic arch and aberrant left subclavian artery in a white Bengal tiger (Panthera tigris).

A 3-mo-old male white Bengal tiger (Panthera tigris) presented with the chief complaint of regurgitation of solid food since weaning at 2 mo of age. Compared with its littermates, the tiger was in poor body condition and weighed only 10.3 kg when its littermates were estimated at 20-25 kg. Thoracic radiographs showed a megaesophagus cranial to the heart base. A contrast esophagram more clearly outlined the megaesophagus, and fluoroscopy demonstrated normal motility of the caudal esophagus. Endoscopic examination revealed a structure coursing dorsally from right to left over the esophagus and a constrictive band on the left of the esophagus at the heart base. Nonselective angiography confirmed the presence of a persistent right aortic arch, as well as an aberrant left subclavian artery. A left fourth intercostal thoracotomy was performed, and the ligamentum arteriosum was double ligated and divided. The left subclavian artery did not cause significant compromise of the esophagus and was not manipulated at surgery. The tiger recovered well from anesthesia and surgery. Solid food was slowly introduced over a 2-mo period without any regurgitation. The cub gained weight rapidly after surgery.

Animals↗
PubMed2001

Fatal pentastomiasis in captive African dwarf crocodile hatchlings (Osteolaemus tetraspis).

Six eggs from a captive African dwarf crocodile (Osteolaemus tetraspis) nest were artificially incubated. Two abnormal hatchlings with incomplete absorption of their yolk sacs died within 48 hr of hatching. No parasites were detected grossly or histologically in either hatchling. The remaining four apparently healthy hatchlings died without clinical signs at 3 wk of age, 1 wk after being fed live wild-caught fish and commercially raised goldfish. Necropsy revealed multiple white small wormlike organisms within the lungs, liver, and gastrointestinal tract of all four hatchlings. Histopathologic cross sections suggested that pentastomiasis was the cause of death, and whole parasites were identified as Sebekia mississippiensis. This infection was probably contracted by ingestion of live fish intermediate hosts infected with nymphal parasites. Avoiding the use of infected live fish or untreated fish products can prevent mortality of hatchling crocodilians caused by S. mississippiensis within zoological collections.

Alligators and Crocodiles↗
PubMed2000

Acute ibuprofen toxicosis in a ferret.

A 20-month-old 1.44-kg (3.2-lb) castrated male ferret was examined because of vomiting, defecating in an abnormal location, dyspnea, and signs of depression. Within 5 minutes of initial evaluation, the ferret became nonresponsive to all stimuli except deep pain. Despite intensive supportive treatment, the ferret died. Toxicologic analyses for ibuprofen were performed on serum, urine, and liver, using gas chromatography and mass spectrophotometry. Serum ibuprofen concentrations were 245 micrograms/g before and 269 micrograms/g after death. Acute ibuprofen toxicosis may cause severe lethargy progressing to coma, apnea, and death in ferrets. Ibuprofen toxicosis should be considered in differential diagnoses for ferrets with signs of depression, with or without clinical signs of gastrointestinal tract dysfunction.

Analgesics, Non-Narcotic↗
PubMed2000

Identification of monozygotic twin chimpanzees by microsatellite analysis.

Zygosity determination is important for epidemiological, biological, obstetric, and prognostic studies in both human and nonhuman primates. In this study, microsatellite loci were used to screen a pair of chimpanzee (Pan troglodytes) twins and their parents. The twins share identical alleles at all loci tested. The probability of dizygotic origin is estimated to be 2.9 x 10(-11). Even after excluding linkage of loci on the same chromosome, the probability is still low enough (3.7 x 10(-9)) to exclude dizygotic origin. MHC typing was also done on Patr-DRB and Patr-DQB loci and the twins share identical alleles at both loci, consistent with the microsatellite results. Together these results demonstrate a monozygotic origin for the chimp twins. Our results suggest that microsatellite analysis is a powerful method for zygosity determination, which can be screened reliably and efficiently.

Animals↗
PubMed2000

Proliferative osteoarthritis and osteoarthrosis in 15 snakes.

Fifteen snakes representing seven species with segmental, proliferative osteoarthritis and osteoarthrosis of the spine were presented for examination. All the snakes were captive, privately owned, and fed domestic rodents. Physical examination, radiography, blood culture, bone culture, necropsy, and histopathology were performed on each snake. All the snakes had similar physical examination, radiologic, and necropsy findings. There were three histologic types of lesions: active bacterial osteoarthritis, predominantly noninflammatory osteoarthrosis with multifocal inflammation suggestive of chronic bacterial osteoarthritis, and noninflammatory lesions consistent with osteoarthrosis without evidence of inflammation or bacteria. These findings suggest that all these snakes represent a single disease process, bacterial infection of the vertebrae. The different histologic lesions observed in these snakes may be a continuum of lesions, from acute to chronic. Gram-negative bacteria were isolated from the blood or bone lesions of 8 of the 15 snakes. In six of these eight snakes, Salmonella species were isolated. Gram-positive bacteria (Streptococcus sp.) were isolated from two other snakes. Blood and bone culture results were well correlated, so blood culture may be effective for detecting active bacterial osteoarthritis.

Animals↗
PubMed2000

Halicephalobus gingivalis (Nematoda) infection in a Grevy's zebra (Equus grevyi).

A 6-yr-old female Grevy's zebra (Equus grevyi) with a disseminated rhabditiform nematode infection is described. Antemortem clinical signs were limited to blindness and abnormal behavior believed to be caused by a recurrent nematode-induced uveitis. Histologic examination of the kidneys, heart, eyes, uterus, and lymph nodes revealed granulomas containing multiple sections of rhabditiform nematodes. Most of the recovered nematodes were larval stages with only a few adult females noted. The adults measured 243-297 microm x 11-16 microm (x = 269 x 14 microm). The distinctive rhabditiform esophagi had corpus:isthmus:bulb proportions of 19:11:5. On the basis of adult morphology, the nematode was identified as Halicephalobus gingivalis. This is the first report of this parasite in a zebra and indicates that this parasitic granulomatous disease should be considered in zebras with neurologic disease.

Animals↗
PubMed2000

Evaluation of a multiple-antigen enzyme-linked immunosorbent assay for detection of Mycobacterium tuberculosis infection in captive elephants.

Mycobacterium tuberculosis has become an important agent of disease in the captive elephant population of the United States, although current detection methods appear to be inadequate for effective disease management. This investigation sought to validate a multiple-antigen enzyme-linked immunosorbent assay (ELISA) for screening of M. tuberculosis infection in captive elephants and to document the elephant's serologic response over time using a cross-sectional observational study design. Serum samples were collected from 51 Asian elephants (Elephas maximus) and 26 African elephants (Loxodonta africana) from 16 zoos and circuses throughout the United States. Infection status of each animal was determined by mycobacterial culture of trunk washes. Reactivity of each serum sample against six antigens was determined, and the linear combination of antigens that accurately predicted the infection status of the greatest number of animals was determined by discriminant analysis. The resulting classification functions were used to calculate the percentage of animals that were correctly classified (i.e., specificity and sensitivity). Of the 77 elephants sampled, 47 fit the criteria for inclusion in discriminant analysis. Of these, seven Asian elephants were considered infected; 25 Asian elephants and 15 African elephants were considered noninfected. The remaining elephants had been exposed to one or more infected animals. The specificity and sensitivity of the multiple-antigen ELISA were both 100% (91.9-100% and 54.4-100%, respectively) with 95% confidence intervals. Mycobacterium bovis culture filtrate showed the highest individual antigen specificity (95%; 83.0-100%) and sensitivity (100%; 54.4-100%). Serum samples from 34 elephants were analyzed over time by the response to the culture filtrate antigen; four of these elephants were culture positive and had been used to calculate the discriminant function. Limitations such as sample size, compromised ability to ascertain each animal's true infection status, and absence of known-infected African elephants suggest that much additional research needs to be conducted regarding the use of this ELISA. However, the results indicate that this multiple-antigen ELISA would be a valuable screening test for detecting M. tuberculosis infection in elephant herds.

Animal Diseases↗
PubMed2000

Use of famciclovir for the treatment of endotheliotrophic herpesvirus infections in Asian elephants (Elephas maximus).

Two juvenile Asian elephants (Elephas maximus) presented with an acute onset of facial edema and lethargy. Examination of the oral cavity of each animal revealed cyanosis of the tip and distal margins of the tongue suggestive of endothelial inclusion body disease (EIBD) of elephants. Whole-blood samples were obtained, and polymerase chain reaction tests confirmed the presence of elephant herpesvirus. The animals were administered famciclovir (Famvir, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania 19101, USA), a potent human anti-herpesvirus drug, in the course of their disease, and recovery followed a treatment regime of 3-4 wk. These are the first known cases of elephants surviving EIBD.

2-Aminopurine↗