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Objective To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Study design prospective, randomized, blinded, crossover trial. Animals Six adult horses weighing 494 ± 33 kg. Methods Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05. Results Meperidine terminal half-life (T1/2 ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all). Conclusion Maximum meperidine concentrations were achieved quickly with a short T1/2 in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. Clinical significance The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.

Chronic lung disease (CLD) is common in individuals living with perinatally acquired HIV (PA-HIV) in southern/eastern Africa. Most of the UK PA-HIV population are African. We conducted a case-note review of CLD in 3 UK PA-HIV cohorts (n = 98). Bronchiectasis or obliterative bronchiolitis occurred in 8.1% of patients and ring/tramline opacities occurred in 19.2% of patients on chest radiograph. There may be unrecognized and underdiagnosed CLD among PA-HIV in the UK.

Objective Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Study design Masked, randomized, cross-over, Latin square design. Animals A group of eight healthy adult horses Methods Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg–1 (LD), 0.04 mg kg–1 (MD), 0.08 mg kg–1 (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental analysis. Pharmacodynamic data collected for 24 hours after treatment included thermal nociceptive threshold, heart rate (HR), respiratory rate (fR) and rectal temperature, and analyzed using mixed-effects linear models. Results Mean (± standard deviation) hydromorphone terminal half-life (t1/2), systemic clearance and apparent volume of distribution at steady state (Vdss) were 18.1 ± 18.6, 34.0 ± 12.8, and 41.3 ± 32.5 minutes, 66.6 ± 5.3, 550.0 ± 76.4, and 92.7 ± 13.9 mL kg–1 minute–1, and 1118 ± 369, 1460 ± 325 and 2242 ± 950 mL kg–1 for treatments LD, MD and HD, respectively. Thermal threshold increased significantly compared to baseline for all treatments for up to 12 hours. HR was elevated above baseline in treatments LD, MD and HD, extending to 30, 15 and 105 minutes after treatment, respectively. Respiratory rate was elevated above baseline in treatments MD and HD from 30 to 195 minutes and from 45 to 480 minutes after treatment, respectively. Temperature was elevated above baseline in treatment HD until 255 minutes after treatment. Conclusions Hydromorphone exhibited a short t1/2, rapid clearance and large Vdss in horses. It also provided a dose-dependent increase in thermal threshold with associated increases in HR, fR and rectal temperature. Clinical relevance Hydromorphone 0.04 mg kg–1 provided clinically relevant thermal antinociception with minimal adverse effects.

The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis. We tested the feasibility of using microneedle (MN) patches as an alternative to iontophoresis to administer pilocarpine to induce sweating. Pilocarpine‐loaded MN patches were developed. Both MN patches and iontophoresis were applied on horses to induce sweating. The sweat was collected to compare the sweat volume and chloride concentration. The patches contained an array of 100 MNs measuring 600 μm long that were made of water‐soluble materials encapsulating pilocarpine nitrate. When manually pressed to the skin, the MN patches delivered >0.5 mg/cm2 pilocarpine, which was double that administered by iontophoresis. When administered to horses, MN patches generated the same volume of sweat when normalized to drug dose and more sweat when normalized to skin area compared to iontophoresis using a commercial device. Moreover, both MN patches and iontophoresis generated sweat with comparable chloride concentration. These results suggest that administration of pilocarpine by MN patches may provide a simpler and more‐accessible alternative to iontophoresis for performing a sweat test for the diagnosis of CF.

Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidime in neonatal foals was determined. Six healthy one to two-day-old foals were given 25 mg/kg of ceftazidime by IV and IM routes in a cross-over design, with a 48-h washout period between doses. Non-compartmental analysis was used to estimate plasma pharmacokinetic parameters. Median t1/2 was 2 h and median AUC0-last was 364 µg h/ml for both IV and IM administration. Median Cmax after IM administration was 101 µg/ml, with a median Tmax of 0.7 h. Relative bioavailability of IM injection was 90%. There were no statistically significant differences between estimated IV and IM pharmacokinetic parameters. Plasma concentrations remained above the human CLSI susceptible breakpoint for Enterobacteriaceae for over 8 h following IV and IM administration.

OBJECTIVE To determine the effect of xylazine on intracranial pressure (ICP) in standing compared to isoflurane-anesthetized horses. DESIGN Prospective, crossover study design. SETTING University Teaching Hospital. ANIMALS Six adult horses donated to the University. Horses were determined to be healthy via physical examination, complete blood count, and neurological evaluation. INTERVENTIONS Horses were anesthetized, maintained on isoflurane in oxygen in left lateral recumbency, and ventilated to normocapnia. Horses were instrumented for intraparenchymal measurement of ICP, invasive blood pressure, pulse oximetry, and end tidal gas analyzer. Xylazine 1 mg/kg was administered IV and ICP, systolic arterial pressure, mean arterial pressure (MAP), diastolic arterial pressure, and heart rate were recorded and cerebral perfusion pressure (CPP) was calculated for the following 15 minutes. Twenty-four to 36 hours following anesthetic recovery, xylazine 1 mg/kg was administered IV and ICP, heart rate, and Doppler blood pressure (BPdop) on the tail were monitored for 15 minutes. MEASUREMENTS AND MAIN RESULTS There was a decrease in ICP following administration of xylazine in anesthetized horses (P

OBJECTIVE To determine whether an association exists between direct intracranial pressure (ICP) measurement and ultrasonographic measurement of optic nerve sheath diameter (ONSD) in anesthetized and standing horses. DESIGN Cross-sectional study performed on a convenience sample of healthy adult horses. SETTING University teaching hospital. ANIMALS Eight adult horses donated to the University. Enrolled horses were free of abnormalities on physical examination, CBC, neurological evaluation, and ophthalmological examination. MEASUREMENTS AND MAIN RESULTS Horses were anesthetized in lateral recumbency for placement of an ICP transducer. Three head positions (neutral, elevated, and lowered) were used to alter ICP. ICP and ONSD in 2 directions (D1 and D2) were recorded at 5 and 10 minutes after position change to elevated and lowered. ICP and ONSD measurements were repeated in standing sedated horses 24-36 hours after recovery from anesthesia. Linear regressions were performed with ICP as the dependent variable and ONSD as the independent variable by head position and times. Linear regressions were also performed for change from neutral under anesthesia, with ONSD as the independent variable and ICP as the dependent variable, by head position and times. Significance was set at P

Objective To compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration. Study design Randomized, masked, crossover design. Animals A total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg. Methods Horses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (fR), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant. Results The mean ± SD hydromorphone terminal half-life (t1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute⁻1 kg⁻1 and 1125 ± 309 mL kg⁻1. The t1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p Conclusions and clinical relevance IM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration. IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.

Rhodococcus equi , a soil saprophyte, is a common cause of pneumonia in foals and a frequent opportunistic pathogen in immunosuppressed people. Because it is widespread in the environment, R. equi can be detected in the feces of most horses. However, the exact timing and rate of shedding relative to infection is unknown. The objectives of this study were to quantify shedding of R. equi in mares and foals after experimental infection of foals with 2 different inocula and to determine the effect of composting on concentrations of R. equi in contaminated bedding. Foals were infected intratracheally with virulent R. equi using inocula of 1 × 10 7 CFU/mL (n = 16) or 1 × 10 6 CFU/mL (n = 12) at 23 ± 2 days (range 21 to 27 days) of age. Fecal samples were collected from mares and foals prior to infection and on days 3, 7, and 14 post-infection for quantitative culture of total and virulent R. equi . Waste from the horses was composted for 7 days. Concentrations of total and virulent R. equi in foal feces were significantly higher on day 14 post-infection compared to day 0, regardless of inoculum size. Concentration of total R. equi in mare feces was significantly higher on days 3, 7 and 14 compared to day 0 regardless of inoculum size, whereas shedding of virulent R. equi only increased on day 14 post-infection. Composting for 7 days significantly decreased concentrations of total R. equi and virulent R. equi by an average of 1.08 ± 0.21 and 0.59 ± 0.26 log 10 CFU/g, respectively.

Peripheral blood mononuclear cells (PBMCs) were obtained from 6 foals1 week of age, 6 foals between 3 and 4 months of age, and 10 adult horses. PBMCs were stimulated with concanavalin A (ConA) or calcium ionomycin-phorbol myristate acetate (CaI-PMA) and the frequency of interferon IFN-gamma and IL-4 secreting cells was measured using an equine-specific ELISPOT assay. The number of IFN-gamma secreting cells was significantly lower in both groups of foals than in adult horses regardless of the mitogen used for stimulation. The number of IFN-gamma secreting cells was significantly higher in cells stimulated with CaI-PMA than in cells stimulated with ConA. In cells stimulated with CaI-PMA, the number of IL-4 secreting cells was significantly lower in both groups of foals compared to adult horses. In adult horses only, CaI-PMA stimulation resulted in significantly more IL-4 secreting cells than ConA stimulation. Regardless of age, the ratio of IFN-gamma/IL-4 spot forming cells (SFC) was significantly higher in cells stimulated with CaI-PMA than in cells stimulated with ConA. These findings indicate that the frequency of IFN-gamma and IL-4 secreting cells is lower in foals than in adult horses and that the type of mitogen used has a profound effect on the relative production of both cytokines.

The HIV epidemic in Fiji remains largely uncharacterized. By February 2009, there were 294 confirmed cases; the majority occurred among the 20- to 39-year old age group and resulted from heterosexual contact. There are currently no published data concerning HIV subtypes in Fiji. In this study, venous blood samples were collected as dried blood spots from 35 HIV-positive individuals in Fiji. HIV-1 subtype was determined for 27 (77%) samples and the presence of four different subtypes, with multiple introductions of two, was demonstrated. Subtype distribution was as follows: 16 (59%) were subtype C, 9 (33%) were subtype B, 1 (4%) was subtype A, and 1 (4%) was subtype G. Phylogenetic analysis showed a clear segregation of the Fijian subtype C isolates and previously published Papua New Guinea subtype C isolates as well as multiple introductions of subtype B. These findings represent the first HIV-1 subtype data from the Fiji Islands.

Monocyte phenotype and function were measured in whole blood sampled from a current cohort of human immunodeficiency virus (HIV)-infected individuals attending a large, metropolitan, university-affiliated hospital. There was no significant difference in the prevalence of CD16+ monocytes or the capacity of monocytes to ingest heat-killed Mycobacterium avium complex between these individuals and HIV-uninfected control subjects, regardless of viral load, current CD4+ T cell count, nadir CD4+ T cell count, or time since diagnosis of HIV infection. CD16+ monocyte prevalence was, however, elevated in patients not currently receiving antiretroviral therapy. We conclude that HIV type 1 infection in the setting of highly active antiretroviral therapy is associated with normal monocyte function and phenotype.