A severe case of disseminated cryptococcosis in a young French bulldog living in South-East Queensland caused by Cryptococcus gattii VGII.

BACKGROUND: Cryptococcus is one of the most common systemic mycosis worldwide, infecting young adults of the large to giant breed dogs. Infection is commonly acquired from the environment via the sinonasal cavity as the main portal of entry. It either remains there, or spreads to the central nervous system (CNS) and the eye (optic nerve and retina) by penetration of the cribriform plate, or haematogenously to other viscera. Lung involvement is uncommon in cats and dogs in contrast to human and equine patients. Whilst there is a wide genetic diversity amongst Cryptococcus neoformans and Cryptococcus gattii isolates along the West Coast and Northern parts of Australia, the molecular diversity of C. gatti is considered very low on the East Coast of Australia, with a huge preponderance of VGI cases. We report on a young small breed brachycephalic dog that presented with extreme gastrointestinal and respiratory signs, but no CNS involvement. It is the first reported case of C. gattii VGII genotype in a companion animal from Queensland. CASE REPORT: A 9-month old female entire French Bulldog presented initially for diarrhoea. Clinical progression was accompanied by the development of respiratory signs, so the patient was referred to a 24 h care facility. Following hospitalisation, the patient became hypoxemic requiring mechanical ventilation. A bronchoalveolar lavage performed antemortem confirmed abundant Cryptococcal spp. Further culturing and genotyping identified the species as Cryptococcus gattii VGII. Post-mortem findings indicated gross gastrointestinal and mesenteric involvement, with possible dissemination to the local mesenteric lymph node and lungs. CONCLUSION: This case describes a rare example of a Cryptococcus spp suspected of disseminating from the gastrointestinal tract to the lungs, without involvement of the CNS. The observation of this finding in a small brachycephalic breed is unusual, and the finding of genotype VGII on the East Coast of Queensland is extremely unusual as there is no prior travel history of the dog or owners. The presence of a miliary lung pattern with primary gastrointestinal disease in a small breed dog warrants adding cryptococcosis to the differential diagnosis.

SnakeMap: four years of experience with a national small animal snake envenomation registry.

SnakeMap is a national cloud-based, veterinary snakebite registry. It was designed to prospectively collect data of the clinical circumstances and temporospatial information on cases of snake envenomation in dogs and cats. We herein introduce the project and summarise the data from the first 4 years of SnakeMap. The registry is a veterinary community-based online database allowing case entry from veterinary hospitals across Australia. Registry data comprise hospital characteristics, patient characteristics, envenoming snake type, treatment and outcome variables, including time and geolocation of the snake bite. We present summative information on select key variables from the SnakeMap registry (1 July 2015 to 30 June 2019). Twenty-eight hospitals from 6 states/territories entered 624 cases into the registry, including 419 dogs (67%) and 205 cats (33%). Bite time was available in 216 animals of which 90 (42%) were reported to be bitten in the 3 hours between 03:00 pm and 05:59 pm; median bite to presentation interval was 60 (interquartile range [IQR] 30, 211) minutes in dogs and 95 (IQR 41, 238) minutes in cats. Bites occurred in the owner's yard in 356 dogs (85%) and 53 cats (26%). A snake venom detection kit was used in 172 cases (28%) and antivenom was administered in 523 cases (85%). Most animals (n = 534, 88%) survived to discharge (median hospitalisation of 25 [IQR 16, 62] hours). SnakeMap effectively collects relevant clinical data from dogs and cats with presumed snake bite and provides locally specific information on the epidemiology of snake envenomation in small animals.

A general-practice study of the efficacy and tolerability of metoprolol in mild essential hypertension.

The efficacy and tolerability of metoprolol (100 mg once a day) were assessed in general practice in 6713 newly-diagnosed or previously-treated hypertensive patients in an open study of eight weeks' duration. In 3534 mildly-hypertensive patients who were eligible for the efficacy analysis, the mean blood pressure level was reduced by 19/10 mmHg; 68% of the patients achieved diastolic blood pressures below 90 mmHg by the end of the assessment period. Of 6557 patients who were eligible for the tolerability analysis, only 5.6% of patients withdrew because of adverse events. The incidence of adverse events diminished considerably from the clinic assessment at four weeks (20%) to that at eight weeks (11%). At the completion of the study, 92% of the mildly-hypertensive patients were to continue with metoprolol, either as monotherapy (including 64% of patients who were receiving 100 mg once a day and 6% of patients who were receiving 50 mg once a day), or as combination therapy. Analysis of the large subgroup of mildly-hypertensive elderly patients (n = 1214) and of moderately-hypertensive patients, whose diastolic pressures exceeded the set upper limits (n = 2505), showed similar efficacy and tolerability results. Sixty-eight per cent of the former and 47% of the latter demonstrated satisfactory control of blood pressure. These results show that the majority of mildly-hypertensive patients can be controlled with 50-100 mg of metoprolol once a day.

Correlations between common tests for assessment of liver damage: indices of the hepatoprotective activity of promethazine in carbon tetrachloride hepatotoxicity.

The effects of promethazine (PM) on different aspects of the hepatotoxic action of CCl4 in the rat were investigated with the objective of finding rapid and reliable indicators of hepatoprotective effects. The study was based on definitive histological assessment of liver damage caused by CCl4 in the presence and absence of PM: PM (78 mumol kg-1, i.p.) protected against CCl4-induced hepatic necrosis 24 h after a low dose of CCl4 (1.3 mmol kg-1) but not against a higher dose (13.0 mmol kg-1). The large increases in plasma activities of GOT, GPT and LDH produced by dosing with CCl4 were partially inhibited by the administration of PM. PM and CCl4 caused a synergistic and long-lasting decrease in body temperature (2-3 degrees C for 8-10 h). Modifying the toxicity with PM, together with a low dose of CCl4, helped to minimize secondary effects of CCl4, to clarify the sequence of toxic events, and to assess the sensitivity of some standard tests of hepatotoxicity. Simultaneous measurement of over 20 commonly used biochemical screening tests in individual animals 3 or 6 h after treatment permitted direct correlation of a wide variety of concentrations, activities and effects. For example, liver CHCl3 concentrations (as a measure of CCl4 metabolism) correlate strongly with increases in diene conjugation of microsomal lipids (as a measure of CCl4-induced lipid peroxidation); malonaldehyde production appears to be less sensitive as a measure of lipid peroxidation in vivo than diene conjugation. The changes induced in each parameter and the correlations between them are discussed with reference to the overall nature of the hepatotoxic reaction and its modification by PM.

Rapid, sensitive determination of unchanged promethazine in biological material using a nitrogen-selective flame ionization detector. Identification of metabolites by gas chromatography-mass spectrometry.

A rapid, sensitive method has been developed to study the kinetics of unchanged promethazine (PM) in biological material using a nitrogen-selective flame ionization detector (N-FID). Unchanged PM is distinguished from its desmethyl metabolite. Sample clean-up of several biological fluids (rat plasma, blood, urine, liver and kidney homogenates) was studied and gas chromatographic (GC) conditions optimized. Usually 50 microliters-1.0 ml samples are extracted into n-heptane by shaking with NaOH, re-extracted into H2SO4 and again extracted into n-heptane by addition of NaOH. Finally, the organic phase is separated, concentrated under N2 and PM determined by N-FID. However, a rapid, single-step method requiring only NaOH extraction into n-heptane may be used whenever GC background permits. Imipramine is used as an internal standard for calibration by peak height ratios in the overall range 5--1500 ng PM per sample. Recovery of both methods is high (97--99%) but precision of the single-step method is lower (relative S.D. 10% versus 3--4%). Use of sample volumes up to 1 ml allows accurate determination of concentrations as low as 10 ng/g. Examples of applications to commonly used animal models employing PM are given and simple adaptation for clinical samples suggested.

Two rapid methods for the simultaneous gas-liquid chromatographic determination of carbon tetrachloride and chloroform in biological material and expired air.

Two simple gas-liquid chromatographic techniques were developed for the simultaneous determination of CCl4 and CHCl3 in biological material and expired air and principally for use in the well-known CCl4-induced hepatotoxicity model: a non-extractive head-space analysis by flame ionization detection (FID) and a single-step toluene extraction using electron-capture detection (ECD). For head-space analysis, blood or liver homogenate is incubated with buffer in sealed reaction vials and the head-space vapour sampled for FID determination. Absolute signal response to CCl4 and CHCl3 was used for calibration in the range 5-500 microgram per gram of biological material. The method is reasonably accurate, e.g. CCl4 in liver homogenate 98 +/- 21.8 (S.D.) %, in blood 94 +/- 13.3%, but the precision is poor (rel. S.D. 10-20%). Air samples in volumes of up to 2 ml may be determined by direct FID injection. The ECD sensitivity of to CCl4 and CHCl3 permits determination of microsamples (50-500 microliters) of blood and liver homogenate by extraction with buffer into toluene containing an internal standard (propyl iodide). The linear range of the detector allowed calibration by peak area ratio in the concentration range (10-1500 ng of CCl4 or CHCl3 per millilitre of toluene. The accuracy of the method is high, e.g. in blood CHCl3 101 +/- 9.5 (S.D.)%, CCl4 100 +/- 15.2%, as is the precision: rel. S.D. ca 5% for both CCl4 and CHCl3. For elimination studies, CCl4 and CHCl3 in air may be trapped in toluene and determined by ECD. Recovery of known amounts of CCl4 and CHCl3 from air chamber was high: 100 +/- 4.7 (S.D.)% and 111 +/- 10.9%, respectively, and reduction of CCl4 to CHCl3 by the trapping system negligible (less than 0.01%). Cross-checking of the methods and application to the commonly used CCl4 hepatotoxicity model is demonstrated.