Chemotherapy of T b brucei infection: Use of DFMO, diminazene aceturate, alone and in combination

The therapeutic activity of diminazene aceturate, difluoromethylornithine (DFMO) and a combination of the two agents was investigated in experimental Trypanosoma brucei brucei infections in mongrel dogs. The criteria used in the assessment of the trypanocidal effect of these compounds included the examination of the blood for the parasite, as well as clinical and haematological changes at intervals following treatment. Diminazene aceturate (7 mg/kg intramuscularly), DFMO (300 mg/kg/day orally in three divided doses for six days) and the combination of diminazene aceturate (7 mg/kg intramuscularly) and DFMO (300 mg/kg/day orally for six days) produced an intermittent aparasitemia in the dogs. Relapse infection occurred in all the three groups, but the period of aparasitemia produced by the combination of the agents was longest. The packed cell volume, haemoglobin concentration and red cell count values decreased after the dogs were inoculated with the parasite. The values improved slightly following the treatments with the agents or their combination. The total white blood cell counts in the infected dogs indicated leucocytosis, but this improved with drug treatment.     

MAGNETIC RESONANCE, ULTRASOUND AND HISTOPATHOLOGIC CORRELATION OF ACUTE AND HEALING EQUINE TENDON INJURIES

Ultrasonography and MRI have become valuable tools for imaging of tendon injuries. The current study examines the histopathologic basis for the imaging abnormalities. Five injured equine forelimbs and two normal contralateral limbs were studied with high resolution real time ultrasound and MRI. Histologic sections were made and correlated with the diagnostic images. All lesions were readily seen by both modalities. Lesions characterized by hemorrhage, edma, and cellular infiltration were sonolucent on ultrasound and bright on MRI images. MRI returned to normal as fibrogenesis ensued. Ultrasound images remained abnormal until fibrillar reallgnment occured with completion of the healing process. High resolution real time ultrasound and MRI both accurately reflect the tissue abnormalities in acute tendon injuries. The injured horse does appear to be an effective model for correlative imaging studies of tendon injuries.     

The diagnosis of nephrogenic diabetes insipidus in the dog]

Nephrogenic diabetes insipidus is characterized by polyuria, hyposthenuria and compensatory polydipsia. With conventional clinical and laboratory examinations the diagnosis can be established and the differential diagnostic diseases excluded. In order to verify the diagnosis, differentiate the condition from central and nephrogenic diabetes insipidus and rule out psychogenic polydipsia, additional laboratory studies are required: of these, the concentration test, modified Carter-Robbins test and AVP stimulation test are described.     

Some Comments on Gerechte Designs

In a companion paper we derived the correct analysis for gerechte designs with uncorrected errors. Here we show that this correct analysis cannot be justified by the usual randomization argument. However, when the regions are rectangular there is a randomization procedure which validates an analysis with three separate error terms. We also outline other developments in design and analysis that may be more satisfactory.     

Matching spatial databases and quantitative models in land resource assessment

Abstract. Good land management needs information about land resources and the processes taking place in the landscape. In practical land evaluation this information is often expressed in terms of land qualities. The original survey data are stored in geographical information systems where they can be used to estimate the values of appropriate land qualities. Land qualities are complex attributes of land used in planning that may be derived from the original attributes through empirical threshold or regression models, or from process-based deterministic or stochastic simulation models. In order to improve estimates of the distribution of land qualities in space and time, and hence to improve planning decisions, the models require data with a much better spatial resolution than is usually available. The problems and dangers associated with the ad hoc linkage of simulation models and GIS are discussed. Particular attention needs to be paid to the problems of error propagation and costs and benefits when using models.     

Neurological Manifestations of Niemann-Pick Disease Type C in Cats

Seven Domestic shorthair cats with a lysosomal storage disorder analogous to human Niemann-Pick disease type C, from a breeding colony were studied to characterize the neurological manifestations of this disorder. Affected cats were identified by means of liver biopsies at 4 to 6 weeks of age. Neurological examinations were performed at 2 week intervals from the onset of clinical signs. All cats displayed signs referrable to the cerebellum, with a subtle intention tremor noticed initially at 8 to 12 weeks of age; the disease was rapidly progressive. The tremor became more pronounced, menace response was lost, and severe dysmetria and ataxia developed. Three cats also had signs referrable to other areas of the central nervous system. Cats died or were euthanized between 12 and 43 weeks of age. Pathological findings included accumulation of substrate within neurons throughout the central nervous system, and axonal spheroid formation. The clinical and pathological findings in these cats are comparable to those in the human form of the disease.     

Intradermal testing of horses with chronic obstructive pulmonary disease and recurrent urticaria.

Six horses with chronic obstructive pulmonary disease (COPD) and 8 horses with recurrent urticaria were skin tested with 67 extracts from 58 allergens, including pollens, epidermals, cultivated farm plants, dusts, molds, and insects. Reactions were evaluated 3 times over a 24-hour period immediately after the injections. Results were compared with those obtained from 11 clinically normal horses. All horses had positive skin test reactions. Significant differences was evident between horses with COPD and clinically normal horses for only 3.0% of the possible extract reactions, and between horses with urticaria and clinically normal horses for only 4.5% of the possible extract reactions. Horses with COPD or urticaria had greater total percentage of allergen extract reactions than did clinically normal horses. Positive reactions were observed at all 3 evaluation periods, and late-onset reactions were not always preceded by positive reaction at earlier periods. All horses with COPD or urticaria had at least 1 skin test reaction that exceeded the mean +/- 2 SD, as calculated for each of the 67 extracts for the group of clinically normal horses.     

Analysis and pharmacokinetics of cimaterol in growing Holstein steers.

Pharmacokinetic parameters for the beta 2-adrenergic agonist, cimaterol (CIM), were determined in growing Holstein steers. Compartmental analysis was used after measurement of CIM in body fluids by affinity chromatography and HPLC using UV detection. Recoveries from spiked plasma and urine standards were 70 +/- 1.2% and 68 +/- 1.1%, respectively. The minimum detection level in plasma was 1 ng/mL and the average CV was 5.1% for concentrations that ranged from 1 to 30 ng/mL. Four steers (276 +/- 24 kg) received 15 mg of CIM by bolus intravenous injection. Plasma CIM levels declined in a biphasic manner with half-lives of 2.5 min for the distribution phase and 54 min for the elimination phase. A two-compartment open model was used to describe the disappearance of CIM and the following pharmacokinetic parameters were obtained: central compartment volume (Vc) = .76 L/kg, apparent volume of distribution (Vd) = 4.1 L/kg, and transfer rate constants from the central to peripheral compartment (k12) = .177/min, from the peripheral to central compartment (k21) = .054/min and elimination from the central compartment (kel) = .074/min. After 8 h, total urinary CIM accounted for only 18.3% of the administered dose. Results suggest that circulating concentrations of CIM in growing steers are influenced by its accumulation in an unidentified peripheral pool and its conversion into unknown metabolite(s) before elimination.     

Release of tumor necrosis factor-alpha from bovine alveolar macrophages stimulated with bovine respiratory viruses and bacterial endotoxins

The release of tumor necrosis factor-alpha (TNF-) from cultured bovine alveolar macrophages (BAM) was evaluated following stimulation of BAM with bovine herpesvirus-1 (BHV-1), parainfluenza-3 (PI-3) virus, bovine respiratory syncytial virus (BRSV), Escherichia coli 0111:B4 endotoxin, Pasteurella haemolytica type 1 endotoxin, Pasteurella multocida endotoxin, and virus/endotoxin combinations. A cytotoxic assay system using Georgia bovine kidney cells as targets was used to measure TNF- activity. The cytotoxic activity was neutralized by an anti-human TNF- monoclonal antibody.

Stimulation of BAM with 1 median tissue culture infectious dose (TCID₅₀) of live or ultraviolet (UV)-inactivated PI-3 virus/cell resulted in release of TNF- in significantly (P<0.05) higher amounts than sham-induced BAM. The quantities of TNF- released after live or UV-inactivated BHV-1 or BRSV induction were not significantly higher than sham-induced BAM. E. coli 0111:B4, P. haemolytica type 1 and P. multocida endotoxins stimulated TNF- release in a dose-dependent manner. Sequential exposure of BAM to 1 TCID₅₀ per cell of either live BHV-1, PI-3 virus or BRSV and then 5 μg ml⁻¹ of either E. coli 0111:B4, P. haemolytica type 1 or P. multocida endotoxin caused a significant (P<0.05) reduction in detectable TNF- in seven of nine virus/endotoxin combinations tested, when compared with 5 μg ml⁻¹ of endotoxin alone. Parainfluenza-3 virus/endotoxin combinations stimulated higher TNF- release when compared with other virus/endotoxin combinations. Five out of six test animals had serum-neutralizing antibodies to PI-3 virus, one out of six had serum-neutralizing antibodies to BHV-1, and two out of six had serum-neutralizing antibodies to BRSV, suggesting a possible relationship between serum neutralizing antibodies and TNF- release from in vitro cultivated BAM.     

Eastern equine encephalitis in a flock of emus (Dromaius novaehollandiae).

Eastern equine encephalitis (EEE) was diagnosed in a flock of emus in southeastern Louisiana. The outbreak involved juvenile and adult breeders ranging in age from 20 to 36 months, with an attack rate of 76% and a case fatality rate of 87%. The diagnosis was confirmed by isolation and characterization of the viral agent, and by detection of EEE antibody in two recovered emus. High mortality was preceded by marked depression, hemorrhagic diarrhea, and emesis of blood-stained ingesta. On postmortem examination, hemorrhagic enteritis and multiple petechia of viscera were observed. Microscopic changes included severe necrosis of hepatocytes, intestinal mucosa, and necrotizing vasculitis of the spleen and lamina propria of the intestine. No nervous system lesions were observed. This outbreak occurred concurrently with EEE in horses and was attributed to unseasonably heavy rainfall with an abundance of arthropod vectors and proximity to free-living reservoir host species.