Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals.

The objectives of this study were to determine the plasma and pulmonary disposition of gamithromycin in foals and to investigate the in vitro activity of the drug against Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Rhodococcus equi. A single dose of gamithromycin (6 mg/kg of body weight) was administered intramuscularly. Concentrations of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection. The minimum inhibitory concentration of gamithromycin required for growth inhibition of 90% of R. equi and S. zooepidemicus isolates (MIC(90)) was determined. Additionally, the activity of gamithromycin against intracellular R. equi was measured. Mean peak gamithromycin concentrations were significantly higher in blood neutrophils (8.35±1.77 µg/mL) and BAL cells (8.91±1.65 µg/mL) compared with PELF (2.15±2.78 µg/mL) and plasma (0.33±0.12 µg/mL). Mean terminal half-lives in neutrophils (78.6 h), BAL cells (70.3 h), and PELF (63.6 h) were significantly longer than those in plasma (39.1 h). The MIC(90) for S. zooepidemicus isolates was 0.125 µg/mL. The MIC of gamithromycin for macrolide-resistant R. equi isolates (MIC(90)=128 µg/mL) was significantly higher than that for macrolide-susceptible isolates (1.0 µg/mL). The activity of gamithromycin against intracellular R. equi was similar to that of azithromycin and erythromycin. Intramuscular administration of gamithromycin at a dosage of 6 mg/kg would maintain PELF concentrations above the MIC(90) for S. zooepidemicus and phagocytic cell concentrations above the MIC(90) for R. equi for approximately 7 days.

Efficacy of a 2-dose regimen of a sustained release ceftiofur suspension in horses with Streptococcus equi subsp. zooepidemicus bronchopneumonia.

The efficacy and safety of sustained release ceftiofur administered twice, 4 days apart, for treatment of horses with naturally acquired Streptococcus equi subsp. zooepidemicus (Strep. zoo.) pneumonia was evaluated in a multicenter, placebo-controlled, double-blinded, randomized clinical trial. The study included 373 horses (278 treated and 95 placebos) with naturally acquired pneumonia. Inclusion in the statistical analyses for treatment efficacy for Strep. zoo. required recovery of ≥10(4) CFU/mL of Strep. zoo. on the primary isolation plate which resulted in 201 cases (145 treated and 56 placebos) with confirmed Strep. zoo. pneumonia evaluable for treatment success. Therapeutic success was defined by clinical improvement of lower respiratory tract infection at 4 and 9 days after initial dosing, resolution of clinical signs by 15 days, and no recurrence by 25 days. Of the 278 treated horses, 239 (85.9%) completed the 25 day study without additional therapy compared to 50 of the 95 (53.6%) placebo horses. In confirmed Strep. zoo. cases, a clinical cure was achieved in 66.9% of 145 treated horses compared to 32.1% of 56 placebo horses (P = 0.0286). Two doses of sustained release ceftiofur suspension were effective and safe in the treatment of naturally acquired lower respiratory tract infection associated with Strep. zoo. in horses under field use conditions.

Identification of Porphyromonas levii isolated from clinical cases of bovine interdigital necrobacillosis by 16S rRNA sequencing.

Laboratories use pigmentation, antibiotic susceptibility, and biochemical tests to identify anaerobic organisms that play a role in bovine interdigital necrobacillosis (bovine foot rot). In this study, 16S rRNA gene sequencing was used to identify strains to the species level that were originally classified as Prevotella or Porphyromonas spp by conventional phenotype assessment methods. Of 264 qualified strains from ceftiofur clinical trials, 241 isolates were definitively identified by 16S rRNA sequencing as Porphyromonas levii. Similarly, of 275 qualified strains from tulathromycin clinical trials, 156 isolates were definitively identified by 16S rRNA sequencing as P. levii. The predominance of P. levii in this study supports the role of this organism as an associative agent of bovine foot rot and may have implications for routine laboratory diagnosis.

Compressive deformation and damage of muscle cell subpopulations in a model system.

To study the effects of compressive straining on muscle cell deformation and damage an in vitro model system was developed. Myoblasts were seeded in agarose constructs and cultured in growth medium for 4 days. Subsequently, the cells were allowed to fuse into multinucleated myotubes for 8 days in differentiation medium, resulting in a population of spherical myoblasts (50%), spherical myotubes (35%), and elongated myotubes (15%) with an overall viability of 90%. To evaluate cell deformation upon construct compression half-core shaped constructs were compressed up to 40% strain and the resulting cell shape was assessed from confocal scans through the central plane of spherical cells. The ratio of cell diameters measured parallel and perpendicular to the axis of compression was used as an index of deformation (DI). The average DI of myoblasts decreased with strain level (0.99+/-0.03, 0.70+/-0.04, and 0.56+/-0.10 at 0%, 20%, and 40% strain), whereas for myotubes DI decreased up to 20% strain and then remained fairly constant (0.99+/-0.06, 0.55+/-0.06, 0.50+/-0.11). The discrepancy in DI between spherical myoblasts and myotubes at 20% strain was explained by the relative sensitivity of the cell membrane to buckling, which is more pronounced in the myotubes. Sustained compression up to 24 h at 20% strain resulted in a significant increase in cell damage with time as compared to unstrained controls. Despite differences in membrane buckling no difference in damage between myoblasts and spherical myotubes was observed over time, whereas the elongated myotubes were more susceptible to damage.

In vitro susceptibility of porcine respiratory pathogens to tilmicosin.

Bacterial isolates obtained from swine with various clinical diseases were tested for susceptibility to tilmicosin by minimum inhibitory concentration (MIC) and Kirby-Bauer disk diffusion tests using National Committee on Clinical Laboratory Standards methodology. The tilmicosin MIC90 was < or =0.125 microg/ml for Erysiopelothrix rhusiopathiae, < or = 1 microg/ml for Haemophilus parasuis isolates, 8 microg/ml for Actinobacillus suis and Pasteurella multocida type A, 16 microg/ml for toxigenic and nontoxigenic P. multocida type D, 64 microg/ml for Bordetella bronchiseptica, and >128 microg/ml for Staphylococcus hyicus and Streptococcus suis. The results of disk diffusion testing matched well with the MIC results for each pathogen. This in vitro survey of tilmicosin activity against various swine isolates suggests that further clinical evaluation of tilmicosin in swine may be warranted for disease associated with E. rhusiopathiae, H. parasuis, and A. suis but not B. bronchiseptica, S. suis, or S. hyicus.

Clinical comparison of magnetic resonance imaging and nuclear emission imaging in cervical-facial trauma patients.

This retrospective study examined 20 consecutively treated trauma patients who reported a chief complaint of earache or trauma preauricular pain. These individuals were examined with magnetic resonance imaging (MRI), emission study using single photon emission, computerized tomography, and joints auscultation using Doppler sound magnification. There are no statistically significant correlations between clinical findings and imaging studies in trauma patients with complaints of earaches and preauricular pain.

Clinical comparison of temporomandibular joint sound auscultation and emission imaging studies.

Single photon-emission computerized tomography scintigraphy was used to examine 250 patients who previously had temporomandibular joint sounds auscultated and recorded with a Doppler machine. Patients were divided into four groups based on the presence of joint sounds: no sound, reciprocal clicks, reciprocal clicks with crepitus, and crepitus. Statistically significant differences between the groups and the single photon-emission computerized tomography scintigraphy results were determined. There was no correlation between these results and the no sound and crepitus groups, but significant correlation was established between positive results and crepitant joints with reciprocal clicks and noncrepitant clicking joints.

Relationship between forward head posture and diagnosed internal derangement of the temporomandibular joint.

The purpose of this study was to determine if a sample of patients with internal derangement of the temporomandibular joint had a significantly greater amount of forward head posture than did an age- and gender-matched control group. Twenty-two patients at a single head, neck, and temporomandibular joint treatment center, who had the diagnosis of internal derangement of the temporomandibular joint, were compared with a control group of volunteers. The angle of each patient's head position was measured from four photographs (two of the patient sitting and two of the patient standing) with a diagonal line drawn from the spinous process of the seventh cervical vertebra to the tragus of the ear and a horizontal line drawn perpendicular to a plumb line suspended from the ceiling. The angles measured from each of the four photographs were averaged, and this figure was paired with that generated from an age- and gender-matched person in the control group. Results indicated that there was not a significantly greater degree of forward head posture in the experimental group.

Clinical management of a patient following temporomandibular joint arthroscopy.

This case report describes a patient in whom arthroscopic surgery of the temporomandibular joint (TMJ) was used to break up adhesions between the TMJ disc and the articular eminence and therefore improve mobility of the joint. Postsurgical physical therapy procedures used were high voltage electrical stimulation, transcutaneous electrical nerve stimulation, moist heat, ultrasound, ice, mobilization, and therapeutic exercises. Postsurgical goals included normalization of range of motion, elimination of pain, elimination of inflammation, and mandibular function without restriction. Special emphasis is given to an unusually effective mobilization technique used to decrease tenderness in the TMJ. The conservative therapy described may be used for persons with similar symptoms and evaluation findings who do not require surgery. [Waide FL, Bade DM, Lovasko J, Montana J. Clinical management of a patient following temporomandibular joint arthroscopy.

Tolerance of Ultrasound over the Temporomandibular Joint.

The temporomandibular joint (TMJ) is a synovial joint that responds to injury in a similar fashion to other joints in the body. A common adjunct in treating this joint is ultrasound. Some clinicians question the use of ultrasound over the TMJ for fear it might damage the periosteum. Therefore, 2,486 TMJ ultrasound treatments were evaluated retrospectively. Only 14 (.56%) of these reported an abnormal sensation. Only 10 of the 14 showed signs of periosteal ache. Since 2,472 reported no abnormal sensation, it was concluded that a protocol of 100 percent continuous ultrasound set at 1.25 W/cm2 for 3 minutes over the TMJ is tolerated well. J Orthop Sports Phys Ther 1992;15(5):206-208.

Acute closed lock in a patient with lupus erythematosus: case review.

Collagen failure has been shown to result in synovitis, joint adhesions, and internal joint derangement. This case report illustrates the similarities between patients with systemic lupus erythematosus and an internally deranged temporomandibular joint and patients with internal derangement with no lupus erythematosus. If abnormalities in intra-articular collagen tissue lead to adhesion formation and restrict normal mobility during translatory movements, joint mechanics would be compromised. Arthritic changes, vasculitis, and synovitis of systemic lupus erythematosus appear to be contributory factors in this pathophysiologic process. Diagnostic and therapeutic arthroscopic surgery was performed. Acute and chronic signs of synovitis were observed during surgery, and tissue samples were obtained for histologic interpretation.

Mössbauer spectroscopy on oxygenated sperm whale myoglobin: evidence for an Fe3+-O2- coupling at the active center.

57Fe Mössbauer spectra of oxygenated sperm whale myoglobin (MbO2) show a well resolved quadrupole doublet with a temperature dependent splitting. The temperature dependence of the corresponding electric field gradient tensor (EFG) can be calculated from a Fe3+ term scheme for the iron at the active center. The Mössbauer spectra as well as the diamagnetc character of the MbO2-complex are then understood by an exchange coupling of the Fe3+-ion with O2- oxygen molecule ion. The resulting groundstate is a diamagnetic singlet. In order to keep the whole complex diamagnetic at room temperature, an exchange coupling with [J] greater than or equal to 300cm-1 is necessary. As the whole model is in fair agreement with many other spectroscopic data, it is believed to be a good starting point for further detailed calculations.

Investigation of two deoxygenated haemoglobin-haptoglobin complexes by Mössbauer spectroscopy.

Haemoglobin Haptoglobin complexes formed when [Hp+]/[Hb]= 1/1 and [Hp]/[Hb] =2/1 were investigated by 57Fe Mössbauer spectroscopy. Both samples gave a spectrum consisting of a single quadrupole doublet. The temperature dependence of the quadrupole splitting was also identical for both samples. This proves that in both samples the nearest neighbour environment of the iron atom must be the same. A comparison with earlier investigations on myoglobin and haemoglobin indicates that the electronic structure of iron in the HbHp-complexes is similar to that in myoglobin.

The orientation of the electric field gradient tensor in CO-liganded myoglobin.

The EFG-tensor at the position of the Fe-atom of CO-liganded sperm whale myoglobin has been investigated by nuclear gamma-resonance absorption experiments on single crystals. In addition the temperature dependence of the quadrupole splitting of the 14.4 keV level of the iron nucleus was measured. An unambiguous solution for the magnitude and the orientation of the field gradient tensor could only be obtained with the assumption that a C2-axis perpendicular to the haem plane is one principal axis of the electric field gradient tensor. Within this solution the electronic structure of the iron is described by a singlet ground state with Nz = 0.75 and the largest EFG component perpendicular to the haem plane.

Investigation of the electronic term scheme of deoxygenated human haemoglobin by a least squares fit procedure using simultaneously magnetic susceptibility and Mössbauer data.

The calculation of the magnetic susceptibility from a published term scheme for the ferrous iron in deoxygenated human haemoglobin is discussed and a procedure for the simultaneous least squares fit of susceptibility and Mössbauer data is presented. The application of this procedure to the appropriate measurements on human haemoglobin leads to a rearrangement of the low lying electronic levels of the iron. The term schemes received as results of two different sets of susceptibility data used in combination with one set of Mössbauer data overlap with their error bars. The obtained level scheme of the Fe is correlated with the distance of the iron atom from the haem plane and the distance Fe-HIS F8, and some biological implications of these correlations are discussed.