[De novo (type 3) primary intraosseous carcinoma of the jaws]. / Carcinomes intra-osseux primitifs des mâchoires de novo (type 3).

INTRODUCTION: Primary intraosseous carcinoma (PIOC) of the jaws is a rare epidermoid carcinoma from epithelial origin and initially strictly localized within the bone. Histologically, type 3 PIOC (PIOC3) is a de novo primary intraosseous carcinoma. Because of the rarity of this illness, we propose an analysis of a personal case and a revue of the literature. MATERIAL AND METHODS: Two search engines (Pubmed®, Sciencedirect®) were questioned over the period 1976-February 2016 by using following keywords carcinoma, intraosseous, jaws, squamous cell carcinoma. Articles reporting proven PIOC3 and mentioning a precise treatment were selected. RESULTS: Thirty articles concerning 54 patients (sex ratio: 2.4; mean age: 56.8; extreme: 24-78) met the inclusion criterions. The most common symptoms were swelling (53%), pain (44.9%) and infra-alveolar nerve paresthesia (30.6%). The time to diagnosis was 13 weeks. Classification of Zwetyenga et al. showed more than 80% of T2 and T3 stages. The lesions were predominantly mandibular (85.2%) and posterior. Less than a third of patients had lymph node and 10% had distant metastasis. Treatment consisted mostly in a combination of surgery and radiotherapy. With a mean follow-up of 74.8 months, 70.8% were in remission with no evidence of recurrence. We report the case of a 58-year-old patient, with no medical history, complaining since several months about periodontitis with teeth mobility in the right mandibular area. The panoramic X-ray showed a bone lysis at the place of tooth No. 46. In the absence of alveolar healing after extraction and antibiotherapy, a biopsy was made that diagnosed a differentiated keratinizing squamous cell carcinoma. CT scan and MRI showed a mandibular cortical bone loss with involvement of adjacent structures and lymphadenopathy in the ipsilateral IB area. The patient was treated with a combination of chemotherapy and surgery. Postoperative chemo- and radiotherapy is still going on. DISCUSSION: The PIOC3 is a rare tumor, mainly arising in males around 50. Diagnosis should be evoked in the presence of painful swelling and nervous symptoms. The time to diagnosis is long. Tumors are usually seen at late stages. Treatment classically combines surgery and radiotherapy.

Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.

OBJECTIVE: To compare plasma disposition of phenylbutazone and its metabolite oxyphenbutazone after i.v. administration of phenylbutazone in horses and donkeys. ANIMALS: 4 clinically normal horses and 6 clinically normal donkeys. PROCEDURE: Blood samples were collected from each animal at time 0 (before) and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after i.v. administration of a bolus dose of phenylbutazone. Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate model-independent pharmacokinetic variables. RESULTS: Significant differences were found in several pharmacokinetic variables of phenylbutazone and oxyphenbutazone in horses, compared with donkeys. Mean total body clearance of phenylbutazone in horses was fivefold less than that in donkeys (29.3 and 170.3 ml/kg/h, respectively). Mean values for area under the curve and mean residence time in horses (118.3 micrograms/h/ml and 3.6 hours, respectively) were significantly greater than values in donkeys (28.3 micrograms/h/ml and 1.7 hours, respectively). Mean values for apparent volume of distribution at steady state were not significantly different between horses and donkeys. For oxyphenbutazone, mean time to peak concentration in donkeys was significantly less than that in horses (1.6 and 6.4 hours, respectively). CONCLUSION: Phenylbutazone clearance in donkeys was higher than that in horses, and appearance of the metabolite oxyphenbutazone in serum was more rapid in donkeys than in horses, indicating that hepatic metabolism of phenylbutazone is more rapid in donkeys than in horses. CLINICAL RELEVANCE: Because serum concentration of phenylbutazone after single i.v. bolus administration (4.4 mg/kg of body weight) decreases more rapidly in donkeys, compared with horses, phenylbutazone may require more frequent administration in donkeys to achieve therapeutic efficacy.

Pharmacokinetics and cardiopulmonary effects of guaifenesin in donkeys.

Five donkeys and three horses were given guaifenesin, intravenously, by gravity administration, until recumbency was produced. The time and dose required to produce recumbency, recovery time to sternal and standing were recorded. Blood samples were collected for guaifenesin assay at 10, 20, 30, 40, 50, 60 min, and 2, 3, 4 and 6 h after guaifenesin administration. Serum was analysed for guaifenesin using HPLC and pharmacokinetic values were calculated using a computer software package (RSTRIP). In donkeys, heart and respiratory rates and blood pressures were recorded before and at 5-min intervals during recumbency. Arterial blood samples were collected before and at 5 and 15 min intervals during recumbency for analysis of pH, CO2, and O2. ANOVA was used to evaluate dynamic data, while t-tests were used for kinetic values. Respiratory rate was decreased significantly during recumbency, but no other significant changes from baseline occurred. The mean (+/- SD) recumbency dose of guaifenesin was 131 mg/kg (27) for donkeys and 211 mg/kg (8) for horses. Recovery time to sternal (min) was 15 (SD, 11) for donkeys and 34 (SD, 1.4) for horses. Time to standing was 32 min for donkeys and 36 min for horses. Calculation of AUC (area under the concentration-time curve) microgram/mL) (dose-dependent variable) was 231 (SD, 33) for donkeys and 688 (SD, 110) for horses. The clearance (CL) (mL/h.kg) was 546 (SD, 73) for donkeys, which was significantly different from 313 (SD, 62) for horses. Mean residence time (MRT) (h) was 1.2 (SD, 0.1) for donkeys and 2.6 (SD, 0.5) for horses. Volume of distribution Vd(area) (mL/kg) was 678 (SD, 92) for donkeys and 794 (SD, 25) for horses. At the rate of administration used in this study, donkeys required less guaifenesin than horses to produce recumbency, but cleared it more rapidly.

Quantification of phenylbutazone in equine sera by use of high-performance liquid chromatography with a nonevaporative extraction technique.

OBJECTIVE: To develop a sensitive, rugged high-performance liquid chromatography (HPLC) method for the measurement of phenylbutazone (PBZ) in equine sera, using a rapid, nonevaporative extraction technique. SAMPLE POPULATION: Sera from 5 nonexercising adult horses. PROCEDURE: After addition of sodium chloride and acetonitrile to serum samples, reverse-phase HPLC analysis for PBZ and oxyphenbutazone (OXY) was performed directly on extracts, using diode array UV spectrophotometric detection. Probenecid was used as an internal standard. Data were evaluated by standard means of statistical analysis. RESULTS: Recoveries of PBZ, OXY, and probenecid from spiked samples were acceptable (ie, > or = 80%) and within run retention times were reproducible. Chromatograms were free of interfering substances, and linearity of calibration curves was observed throughout operational ranges. Coefficients of variation at each fortified PBZ concentration were in the 5 to 10% range. The method was applicable to analysis of PBZ and OXY in serum extracts from horses dosed with PBZ (4.4 mg/kg of body weight, IV) in a controlled environment. Track samples analyzed by use of this method and a conventional liquid/liquid extraction method gave comparable results (mean deviation, 1.6%) for PBZ concentrations. CONCLUSION: The HPLC protocol described is suitable for measuring PBZ and OXY in equine sera to regulate PBZ administration in horses involved in pari-mutuel racing.

Ovine urinary metabolites of ethoxyquin.

Metabolites of ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) in the urine of sheep and rats were separated and identified by gas chromatography-mass spectrometry (GC-MS). Sheep were given diets containing EQ or EQ.HCl (0.5% of total diet) and urine samples were collected for the first 24 h and for another 24-h period after 12 d of feeding. Rats were given EQ/corn oil (0.08 g EQ/d/rat) orally for 7 d and urine samples were collected at ambient temperature for a 24-h period following 6 d of dosing. The urine samples were extracted with ethyl acetate at pH 5, and the concentrated extracts were analyzed by GC-MS. Ethoxyquin was identified in all sheep urine samples collected during the first 24 h of feeding, and EQ and hydroxylated EQ were identified in all urine samples collected after 12 d of feeding. In contrast, EQ, hydroxylated EQ, and dihydroxylated EQ were identified in urine collected from rats fed EQ for 7 d.

Coagulopathic effects and therapy of brodifacoum toxicosis in dogs.

The clinical signs and laboratory changes of brodifacoum (BDF) intoxicated dogs and their response to vitamin K1 treatment were examined. Brodifacoum, a second-generation anticoagulant rodenticide, was fed to four dogs for 3 consecutive days producing a cumulative dose of 1.1 mg BDF/kg body weight. Clinical observations of the animals were made daily throughout the study. Monitored laboratory parameters included: one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), activated coagulation time (ACT), complete blood counts, thrombocyte counts, and serum chemistry values. Response to vitamin K1 therapy was evaluated clinically and by laboratory tests. Serum BDF concentrations were monitored. Inappetence and hemorrhagic tendencies were exhibited by day 5 postrodenticide exposure. One-stage prothrombin time, APTT, and ACT were 25% greater than time zero values at 24, 24, and 72 hours postdosing, respectively. All laboratory parameters returned to normal within 48 hours of initiating vitamin K1 therapy (0.83 mg/kg orally, TID for 5 days). Serum brodifacoum concentrations were highest (1065-1215 ng/mL) during the 3 days after BDF dosing and were detectable (3.0-7.5 ng/mL) until day 24 postexposure. A mean BDF elimination half-life of 6 +/- 4 days was observed.

A high performance liquid chromatography method for the detection of brodifacoum in serum.

A procedure for the detection of brodifacoum (BDF) in serum was developed. Extraction of BDF was achieved by acidification of 2 ml of serum with 1 ml of 1.5% acetic acid followed by dual extractions with 10 ml diethyl ether and ether: acetonitrile [1:1]. In spiking experiments, 68 +/- 3, 61 +/- 4 and 65 +/- 5% of added BDF was recovered from serum containing 1000, 100 and 25 ng BDF/ml, respectively. Two high performance liquid chromatography solvent systems were used for chromatographic separation (A: 1.5% acetic acid, pH 4.5: acetonitrile [1:2] with 1% dibutylamine; and B:O.2 M tris(hydroxymethyl)aminomethane, pH 7.5:acetonitrile [1:3]). Detection limits were 75 and 3 ng BDF/ml of serum using ultraviolet absorption (254 nm) and fluorescence measurement (313 nm excitation, 375 nm emission), respectively. This method has been used successfully to monitor serum concentrations of BDF in experimental and field cases of exposure.

Determination of brodifacoum and bromadiolone residues in rodent and canine liver.

A method to determine residue concentrations of anti-coagulant rodenticides, brodifacoum (BF) and bromadiolone (BD) in liver was developed, using gas chromatography/mass spectrometry. Nine dogs were given 1.1 mg of BF/kg of body weight, PO, in polyethylene glycol 400, one time. Rats were fed BF or BD (via commercial baits) in amounts from 0.28 to 11.25 mg/kg over 1- to 4-day periods. Fresh liver samples were collected at necropsy from all rats and 3 dogs, ground with Na2SO4, and extracted with CHCl3:MeOH (9:1). After evaporation and silica cartridge purification were performed, residues were oxidized with a 0.16M chromic acid solution, and an oxidation product (4-bromobenzoic acid) was partitioned into CHCl3. The methylated derivative (port derivatization with trimethylanilinium hydroxide) was assayed, using gas chromatography/mass spectrometry. Bromadiolone was detected in livers from rats given greater than 6 mg of BD/kg of body weight, but not in livers of rats given 1.25 mg of BD/kg. In contrast, BF was detected (with one exception) in livers from dogs (given 1.1 mg of BF/kg) and from rats given high (11.25 mg of BF/kg) and low (0.28 mg of BF/kg) doses. This protocol, which does not differentiate between BF and BD because of the formation of a common product after chromic acid oxidation, was used to diagnose anticoagulant toxicosis in 3 dogs, 1 human being and 1 llama naturally poisoned.

Etiologic agents, incidence, and improved diagnostic methods of cantharidin toxicosis in horses.

In addition to the 3-striped blister beetles (Epicauta temexa and E occidentalis), other sources of equine cantharidin toxicosis were identified at the Texas Veterinary Medical Diagnostic Laboratory and included E albida and E attrivittata and the previously incriminated E pardalis and E pennsylvanica. Improved methods for diagnosing cantharidin or blister beetle toxicosis involve partial purification of urine and gastric content extracts, using silica cartridges, followed by analysis, using capillary gas chromatography/mass spectrometry. During a 26-month period, 53 episodes of cantharidin toxicosis in horses were confirmed at our diagnostic laboratory. Concentrations of cantharidin in urine and gastric contents ranged from 0.0003 to 3.50 micrograms/g. Peak incidences were observed in late summer and early fall.

Case studies on second-generation anticoagulant rodenticide toxicities in nontarget species.

Specimens from 10 cases of second-generation anticoagulant rodenticide poisoning in dogs and cats were submitted to the Texas Veterinary Medical Diagnostic Laboratory during 1986 and 1987. The clinical signs most frequently observed were lethargy, dyspnea, and ventral hematomas; common necropsy findings included hemoperitoneum, hemothorax, and pulmonary hemorrhage. In the instances when histopathological examination of the tissue was done, it supported a diagnosis of coagulopathy. The presence of anticoagulants in serum or liver was confirmed by high pressure liquid chromatography, gas chromatography/mass spectrometry, or a combination of the two. Five cases of brodifacoum poisoning, 2 of bromadiolone, and 3 of diphacinone toxicity were verified. Concentrations of these rodenticides ranged from approximately 0.001 to 12 ppm.

Bovine abortion and death associated with consumption of aflatoxin-contaminated peanuts.

Approximately 12% of a herd of 68 crossbred cows aborted third-trimester fetuses after consuming moldy peanuts for 4 days. Further investigation revealed that less than 20% of the herd had access to this supplemental feed. Results of serum biochemical analysis indicated liver damage in the affected cows. All of these cows died within 8 days of aborting. The peanuts contained 77 micrograms aflatoxin B1/g, as determined by liquid chromatography. Tissues were submitted from 1 cow, and liver contained 5 ng aflatoxin B1/g. Results of other laboratory tests were negative for common toxins and abortifacients.

1,3 Butanediol treatment of ethylene glycol toxicosis in dogs.

In order to assess the therapeutic value of 1,3 butanediol in ethylene glycol toxicosis, mixed-bred dogs were given an oral dose of commercial antifreeze at 6 ml/kg of body weight (0 hour) and treated (IV) 7 times at 6-hour intervals with 5.5 ml/kg of body weight 1,3 butanediol solution (20% in physiological saline solution) beginning at 8, 12, and 21 hours. Serum glycolic acid concentration was quantitated by high-pressure liquid chromatography. Three dogs that were given ethylene glycol, but no 1,3 butanediol treatment, died with elevated serum glycolic acid concentrations. Five dogs were given ethylene glycol and 1,3 butanediol treatment. Of 2 dogs treated at 8 hours, 1 survived and 1 died at 39 hours; 1 treated at 12 hours and 1 treated at 21 hours survived; 1 dog died soon (27 hours) after treatment was initiated at 21 hours. Four of the 5 dogs had dramatically decreased serum glycolic acid concentrations after 1,3 butanediol treatment, indicating its effectiveness in inhibiting alcohol dehydrogenase-dependent glycolic acid formation in vivo.

Catastrophic death losses in a dairy herd attributed to type D botulism.

Clostridium botulinum type D intoxication was diagnosed as the cause of death of 42 of 67 lactating cows in a southeast Texas dairy herd over an 11-day period. By necessity, the diagnosis was based on clinicopathologic findings, as the toxin could not, by standard laboratory tests, be demonstrated in affected cattle. The predominant clinical findings were hindlimb weakness/ataxia rapidly progressing to persistent recumbency. Affected cattle were alert until just before death, which occurred without notable agonal movements or respirations after 6 to 72 hours' recumbency. Abnormal laboratory findings included neutrophilic leukocytosis (all affected cattle), proteinuria (most affected cattle), slight elevations of serum aspartate transaminase and low serum inorganic phosphorus (some affected cattle), and patchy areas of hyperemia/congestion of the mucosa in the small intestine (postmortem examination of 3 affected cattle). This report confirms the findings of others with regard to the difficulty of demonstrating the causative toxin in C botulinum type D-intoxicated cattle and presents available information on the clinicopathologic features of this intoxication that may aid in the differentiation of this condition from other causes of down cows.

Methenamine as an induced artifact during extraction of formaldehyde-preserved tissue.

The effect of different basic drug assay procedures on the formation of artifactual methenamine from formaldehyde preserved and nonpreserved tissue was studied. Trichloroacetic acid was compared with ammonium sulfate as a protein precipitant and sodium hydroxide was compared with ammonium hydroxide as a pH modifier. The assay of nonpreserved tissue failed to result in the detection of methenamine. However, when preserved tissue was assayed by procedures which utilized ammonium compounds, large quantities of methenamine were detected using TLC and GC/MS. Trace quantities of methenamine were detected in extracts of preserved autolyzed tissue which was assayed using nonammonium compounds.

Analytical evaluation of urinary excretion of furosemide in barrows.

Market weight barrows were dosed with furosemide IM or orally, and urine (5 barrows) and blood (1 barrow) samples were collected. Extraction procedures and high-performance liquid chromatographic conditions were modified and adapted for analysis of porcine samples. Furosemide was cleared rapidly from plasma, but could be detected in urine 4 to 5 days after administration, using fluorescent or ultraviolet detection. Fluorescent detection was the preferred method for screening for furosemide. Approximately 12% of furosemide was excreted as the glucuronide conjugate.

Diagnosis of ethylene glycol (antifreeze) intoxication in dogs by determination of glycolic acid in serum and urine with high pressure liquid chromatography and gas chromatography-mass spectrometry.

A relatively fast and sensitive high pressure liquid chromatographic (HPLC) and gas chromatographic-mass spectrometric (GC/MS) method was developed for determination of glycolic acid, one of the major metabolites of ethylene glycol, in extracts of canine urine and serum. The procedure involves extraction of glycolic acid with methyl ethyl ketone and derivatization with O-p-nitrobenzyl-N,N'-diisopropylisourea (PNBDI) in ethyl acetate solution. Recovery was greater than 94% from spiked samples. Ethylene glycol and commercial antifreeze were administered to experimental dogs at different dosage levels to reproduce the naturally occurring toxicosis associated with the consumption of commercial antifreeze. Glycolic acid was determined in either the urine or serum or both from these dogs by HPLC and GC/MS. 1,3-Butanediol, a competitive inhibitor of ethylene glycol biotransformation, was administered to one dog concurrently with antifreeze. In that experiment, it was effective in decreasing glycolic acid formation and prevented acute metabolic acidosis, kidney damage, and death.

Waterfowl mortality caused by aflatoxicosis in Texas.

Waterfowl mortality caused by aflatoxicosis occurred in two separate areas in Texas during the 1977-78 wintering season. The first outbreak occurred in snow geese (Anser caerulescens) on the Gulf Coast prairies, followed by an outbreak in mallards (Anas platyrhynchos) in the north-central portion of the state. Aflatoxin B1 levels in geese were 500 ng/g (dry weight). Aflatoxin B1 levels in the second mortality were 10-250 ng/g (dry weight). The exact source of the toxin was not demonstrated in the first outbreak, but in the second outbreak was traced to waste peanuts, which constituted a major portion of the diet of wintering waterfowl in north-central Texas. Aflatoxin B1 levels in the field peanuts collected in the general areas were 110 ng/g.

High pressure liquid chromatographic determination of sodium fluoroacetate (compound 1080) in canine gastric content.

A sensitive high pressure liquid chromatographic method was developed for the determination of sodium fluoroacetate (compound 1080) in canine gastric content. The procedure involves extraction of 1080 with water, methyl ethyl ketone, and dilute base, followed by sample cleanup using octadecylsilane bonded phase cartridges and derivatization in ethyl acetate sodium with O-p-nitrobenzyl-N-N'-diisopropylisourea (PNBDI). The compound was chromatographed on a 10 micrometer silica column, and ultraviolet absorbance at 254 and 280 nm was measured. Recovery was greater than 95% for standard 1080 and in the 70-90% range for spiked samples (1-50 ppm).