Thermal antinociceptive pharmacodynamics of 0.1 mg kg−1 hydromorphone administered intramuscularly in cats and effect of concurrent butorphanol administration

Hydromorphone (HY) has not been objectively assessed as an analgesic in cats. It has been suggested that butorphanol (B) can have a synergistic action with pure μ‐agonists. The aim of this study was to assess the antinociceptive activity of a single dose of HY, and to examine the effect of concurrent B administration on the thermal threshold (TT). Thermal thresholds were measured following IM administration of HY, B, a combination of B and HY (HY‐B), or saline (S). Six cats (four spayed females, two castrated males, 4.75–6.8 kg) were used. Each cat received HY (0.1 mg kg^?1), B (0.4 mg kg^?1), HY (0.1 mg kg^?1), and B (0.4 mg kg^?1) (HY‐B), or S (0.05 mL kg^?1) in a randomized, blinded, cross‐over study design. Each cat received each treatment, with at least 12 days interval between the treatments. All injections were IM randomized to left or right quadriceps using a 24 SWG needle. Twenty‐four hours prior to each study, the thorax of each of the cats was shaved. On the day of the study, TT was measured using a thorax‐mounted thermal threshold‐testing device specifically developed for cats. Skin temperature was recorded before each test and then the heater was activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Three baseline thresholds were recorded over 1 hour before IM injection of test drug. Thermal threshold cut‐off was 55.5 °C. TT was measured at 5 and 15 minutes, every 15 to 360 minutes, every 30 minutes to 8 hours, every hour to 12 hours, and at 24 hours post‐injection. Threshold data were analyzed using an anova with a repeat factor of time. Behavioral adverse effects (dysphoria) were associated with B administration, but not with HY or HY‐B administration (these produced calm euphoria). The control group was stable over time (p = 0.22) (mean threshold 40.15 °C). Overall, there was no period effect, no significant effect of administering B, but a significant effect (raised TT) of administering HY or HY‐B. If the mean value of one of the experimental groups differed from the control group (40.075 °C) by more than 2.355 °C (>42.425 °C), that mean was significantly different from control at p < 0.05 (Bonferroni's t‐tests). This occurred between 15 and 165 minutes for B, from 15 to 345 minutes for HY, and between 15 and 540 minutes for HY‐B. In this model, HY provided up to 5.75 hours of antinociception at 0.1 mg kg^?1, and concurrent administration of butorphanol (0.4 mg kg^?1) decreased the intensity of antinociception over the first 2 hours, but extended the duration of significant antinociception to about 9 hours.     

Origin of the equine middle latency auditory evoked potential

Recordings of the middle latency of the auditory evoked potential (MLAEP) were made in eight conscious ponies. These traces were compared to those made under halothane anaesthesia with and without paralysis of the skeletal muscles. Recordings were also made from percutaneous electrodes placed along the neck with the same stimulus used for the auditory evoked potentials. The results of these experiments were used to deduce the origin of latencies in the auditory evoked potential occurring between 10 and 25 ms after the stimulus. The MLAEP was found to contain two positive peaks between the latencies of 10 and 25 ms. The first of these two peaks was not abolished by halothane anaesthesia or muscle paralysis. The second of these two peaks was abolished by halothane anaesthesia in all but one animal. In this animal the second peak was abolished by muscle paralysis. No peaks of corresponding latency were recorded from the percutaneous electrodes except from one electrode position at the caudal neck in one pony. The first peak of the middle latency auditory evoked potential seen in conscious ponies appeared to be of central nervous orign. The second peak appeared to be of muscular origin, possibly from the external auditory muscles. The second peak may be analogous to the post-auricular waveform described in man.     

Pre-hospital low-volume resuscitation with hemoglobin-glutamer-200 (Hb-200) in a canine hemorrhagic shock model

The Bowen Technique is a unique hands‐on therapy developed by Tom Bowen of Australia in the 1950s–60s and adapted for use in animals by Carol Bennett in 1997. It consists of a specific sequence of gentle, precise rolling moves done with thumb and fingers over muscle and tendon edges, across the direction of tension. A short waiting period follows each set of moves. Definitive mechanism(s) of action remains to be identified; however, autonomic nervous system modulation (heart rate variability studies) has been documented in humans. The technique has also been reported effective for back, hip, neck, and shoulder pain in human studies. Five geriatric dogs (13–16 years old) of various breeds were presented in a case series at a small animal clinic for primary complaints of stiffness, poor ambulation, and difficulty lying down/getting up. Four had hindlimb proprioceptive deficits; three had arthritic changes to coxofemoral joints and/or lumbar spine; three showed active indicators of pain (chronic pacing/panting; irritability; social withdrawal). All were on NSAID and/or nutritional therapy with unsatisfactory results. One dog had acupuncture weekly for over 1 year but no longer tolerated the needles. Treatment consisted of Animal Bowen at weekly or biweekly intervals. Three dogs were pain scored [0–10; average starting score 6.7 ± 0.6 (mean ± S.D.); range 6–7] by owner before and after treatment. All five dogs showed significant positive changes in attitude, and four had notable improvement in ease of ambulation, after the first treatment. Improvement was progressive over treatment course. Average post‐treatment score was 2.3 ± 2.1 (0, 3, 4); average pain score reduction was 4.3 ± 1.5 (range 3–6) after two to six treatments for the three dogs scored. One dog had complete resolution of hindlimb lameness of 5 years duration after three sessions. Animal Bowen, used alone or in conjunction with standard analgesics and other treatments, can be an effective therapy for chronic musculoskeletal conditions in dogs.     

A review of the development of two types of human skeletal muscle infections from microsporidia associated with pathology in invertebrates and cold-blooded vertebrates

Traditionally, the Microsporidia were primarily studied in insects and fish. There were only a few human cases of microsporidiosis reported until the advent of AIDS, when the number of human microsporidian infections dramatically increased and the importance of these new pathogens to medicine became evident. Over a dozen different kinds of microsporidia infecting humans have been reported. While some of these infections were identified in new genera (Enterocytozoon, Vittaforma), there were also infections identified from established genera such as Pleistophora and Encephalitozoon. The genus Pleistophora, originally erected for a species described from fish muscle, and the genus Encephalitozoon, originally described from disseminated infection in rabbits, suggested a link between human infections and animals. In the 1980's, three Pleistophora sp. infections were described from human skeletal muscle without life cycles presented. Subsequently, the genus Trachipleistophora was established for a human-infecting microsporidium with developmental differences from species of the genus Pleistophora. Thus, the existence of a true Pleistophora sp. or spp. in humans was put into question. We have demonstrated the life-cycle stages of the original Pleistophora sp. infection from human muscle, confirming the existence of a true Pleistophora species in humans, P. ronneafiei Cali et Takvorian, 2003, the first demonstrated in a mammalian host. Another human infection, caused by a parasite from invertebrates, was Brachiola algerae Lowman, Takvorian et Cali, 2000. The developmental stages of this human muscle-infecting microsporidium demonstrate morphologically what we have also confirmed by molecular means, that B. algerae, the mosquito parasite, is the causative agent of this human skeletal muscle infection. B. algerae had previously been demonstrated in humans but only in surface infections, skin and eye. The diagnostic features of B. algerae and P. ronneafiei infections in human skeletal muscle are presented. While Encephalitozoon cuniculi has been known as both an animal (mammal) and human parasite, the idea of human microsporidial infections derived from cold-blooded vertebrates and invertebrates has only been suggested by microsporidian phylogeny based on small subunit ribosomal DNA sequences but has not been appreciated. The morphological data presented here demonstrate these relationships. Additionally, water, as a link that connects microsporidial spores in the environment to potential host organisms, is diagrammatically presented.     

The early events of Brachiola algerae (Microsporidia) infection: spore germination, sporoplasm structure, and development within host cells

Brachiola algerae (Vavra et Undeen, 1970) Lowman, Takvorian et Cali, 2000, originally isolated from a mosquito, has been maintained in rabbit kidney cells at 29 degrees C in our laboratory. This culture system has made it possible to study detailed aspects of its development, including spore activation, polar tube extrusion, and the transfer of the infective sporoplasm. Employing techniques to ultrastructurally process and observe parasite activity in situ without disturbance of the cultures has provided details of the early developmental activities of B. algerae during timed intervals ranging from 5 min to 48 h. Activated and nonactivated spores could be differentiated by morphological changes including the position and arrangement of the polar filament and its internal structure. The majority of spores extruded polar tubes and associated sporoplasms within 5 min post inoculation (p.i.). The multilayered interlaced network (MIN) was present in extracellular sporoplasms and appeared morphologically similar to those observed in germination buffer. Sporoplasms, observed inside host cells were ovoid, contained diplokaryotic nuclei, vesicles reminiscent of the MIN remnants, and their plasmalemma was already electron-dense with the "blister-like" structures, typical of B. algerae. By 15 min p.i., the first indication of parasite cell commitment to division was the presence of chromatin condensation within the diplokaryotic nuclei, cytoplasmic vesicular remnants of the MIN were still present in some parasites, and early signs of appendage formation were present. At 30 min p.i., cell division was observed, appendages became more apparent, and some MIN remnants were still present. By two hours p.i., the appendages became more elaborate and branching, and often connected parasite cells to each other. In addition to multiplication of the organisms, changes in parasite morphology from small oval cells to larger elongated "more typical" parasite cells were observed from 5 h through 36 h p.i. Multiplication of proliferative organisms continued and sporogony was well underway by 48 h p.i., producing sporonts and sporoblasts, but not spores. The observation of early or new infections in cell cultures 12-48 h p.i., suggests that there may also exist a population of spores that do not immediately discharge, but remain viable for some period of time. In addition, phagocytized spores were observed with extruded polar tubes in both the host cytoplasm and the extracellular space, suggesting another means of sporoplasm survival. Finally, extracellular discharged sporoplasms tightly abutted to the host plasmalemma, appeared to be in the process of being incorporated into the host cytoplasm by phagocytosis and/or endocytosis. These observations support the possibility of additional methods of microsporidian entry into host cells and will be discussed.     

Haematological and biochemical reference values for the koala (Phascolarctos cinereus)

Haematological and biochemical reference values were established from 45 clinically healthy koalas. Statistical analysis revealed no significant differences for sex and season of sampling. Immature koalas had significantly higher alkaline phosphatase and inorganic phosphate values, and significantly lower total protein concentrations due to low globulins values. Enzyme reference values tended to be wide and could limit their usefulness in detecting disease. In the reference values for leukocytes, neutrophils and lymphocytes, the inclusion of low values which were not actually seen may interfere with the detection of reduced levels due to disease.