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Biomedical subjects

Ray C Boston

Publications and source records attributed to Ray C Boston.

12 recordsLinked to original sources
PubMed2006

Pharmacokinetics of methylprednisolone acetate after intra-articular administration and its effect on endogenous hydrocortisone and cortisone secretion in horses.

OBJECTIVE: To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. ANIMALS: 6 Thoroughbreds. PROCEDURES: In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. RESULTS: A 5-compartment pharmacokinetic-pharmacodynamic model was used to describe the concatenated changes in the plasma concentrations of MP, HYD, and COR and to estimate the instantaneous rate of endogenous HYD production. The median transfer half-life (t(1/2t)) of methylprednisolone from the joint to plasma and elimination half-life (t(1/2e)) from plasma were 1.7 and 19.2 hours, respectively. Maximum plasma concentration of methylprednisolone was 7.26 +/- 3.3 ng/mL at 8 hours, which decreased to 0.11 +/- 0.08 ng/mL at 144 hours after injection. At 3 hours after MPA administration, plasma COR and HYD concentrations were significantly decreased from baseline values (from 2.9 +/- 0.28 ng/mL to 2.10 +/- 1.0 ng/mL and from 61.1 +/- 18.9 ng/mL to 25.7 +/- 12.1 ng/mL, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: The sensitivity of the analytic method used allowed complete description of the related kinetics of MP, HYD, and COR following intra-articular administration of MPA. A single intra-articular administration of MPA profoundly affected the secretion of HYD and COR in horses; secretion of endogenous corticosteroids remained suppressed for as long as 240 hours after injection.

Animals↗
PubMed2005

Subtotal pericardectomy and epicardial excision for treatment of coccidioidomycosis-induced effusive-constrictive pericarditis in dogs: 17 cases (1999-2003).

OBJECTIVE: To determine the history, clinicopathologic findings, and results of surgery for effusive-constrictive pericarditis associated with Coccidioides immitis infection in dogs. DESIGN: Retrospective study. ANIMALS: 17 client-owned dogs that underwent a subtotal pericardectomy and epicardial excision. PROCEDURE: Hospital records from May 1999 to June 2003 were reviewed. Data collected included history, clinicopathologic findings, treatments, and outcome. Follow-up information was obtained via recheck examination and by use of standardized telephone interviews with referring veterinarians and owners. RESULTS: All dogs were of large breeds, and most were male (mean age, 4.66 years). Ten dogs had no prior history of C. immitis infection, and 7 dogs had chronic infection with C. immitis. Having a chronic C. immitis infection reduced the odds of survival, compared with no previous infection. All dogs had clinical signs of right-sided heart failure. All dogs had serum titers (range, 1:8 to 1:256) for antibodies against C. immitis prior to surgery, and titers were not significantly associated with outcome. Predominant echocardiographic findings were thickened pericardium, reduced right ventricular filling, and pleural or pericardial effusion. All dogs underwent a subtotal pericardectomy and epicardial excision and had fibrosing pyogranulomatous pericarditis in biopsy specimens obtained during surgery. The perioperative mortality rate was 23.5%, and the 2-year postdischarge survival rate was 82%. CONCLUSIONS AND CLINICAL RELEVANCE: Surgical treatment via subtotal pericardectomy and epicardial excision is successful at relieving right-sided heart failure in dogs with effusive-constrictive pericarditis secondary to C. immitis infection, but long-term treatment with antifungal agents may still be required.

Animals↗
PubMed2005

Stavudine entry into cerebrospinal fluid after single and multiple doses in patients infected with human immunodeficiency virus.

STUDY OBJECTIVE: To establish the pharmacokinetics of stavudine within the cerebrospinal fluid (CSF) of patients infected with human immunodeficiency virus (HIV). DESIGN: Pharmacokinetic study. SETTING: General clinical research center. PATIENTS: Thirty-six patients infected with HIV; 21 were receiving long-term stavudine therapy, 15 were not (single-dose treatment group). INTERVENTION: After an overnight fast, all patients received a single dose of stavudine 40 mg. Fifteen patients in the long-term treatment group and all 15 patients in the single-dose treatment group were randomized to undergo lumbar puncture 2, 4, or 6 hours after dosing (five patients for each time point from each group). The six other patients in the long-term treatment group underwent lumbar puncture 0 or 8 hours after dosing. MEASUREMENTS AND MAIN RESULTS: Serum stavudine concentrations were obtained just before dosing, 1 hour after dosing (approximate peak), and at the time of lumbar puncture. The CSF was also analyzed for cell counts, protein, and glucose levels. The mean peak serum stavudine concentration in the long-term treatment group was estimated to be 580.7 ng/ml (2.59 micromol/L), occurring approximately 1.3 hours after dosing. The CSF concentrations over 0-8 hours were 0.0-109.9 ng/ml (0.00-0.49 micromol/L) with an overall mean of 51.6 ng/ml (0.23 micromol/L). Mean peak CSF concentration was estimated to be 62.8 ng/ml (0.28 micromol/L), occurring 4.7 hours after dosing. For the 15 patients not taking stavudine, both the serum and the CSF estimated peaks were significantly lower than those of the long-term group: 475.3 ng/ml (2.12 micromol/L) and 40.4 ng/ml (0.18 micromol/L), respectively. However, time to peak was similar at 1.2 hours and 5.0 hours, respectively. In both groups, no correlation was found between CSF and baseline or peak serum stavudine concentrations, CSF white blood cell count, baseline CD4 + lymphocyte count, or plasma viral load. CONCLUSION: Mean CSF stavudine concentrations equaled or exceeded the mean concentration producing 50% of the maximal effect in vivo (EC 50 ) for HIV. The CSF concentrations were higher in the stavudine-experienced patients, indicating that concentrations rise with progressive doses until steady state is reached.

Adult↗
PubMed2005

Effects of oral administration of levothyroxine sodium on concentrations of plasma lipids, concentration and composition of very-low-density lipoproteins, and glucose dynamics in healthy adult mares.

OBJECTIVE: To evaluate glucose and lipid metabolism in healthy adult horses administered levothyroxine sodium (L-T4). ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provide between 7 AM and 8 AM in the morning grain meal for 2 weeks. Four additional horses remained untreated. Serum concentrations of nonesterified fatty acids, triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) were measured and composition of VLDL examined in samples obtained between 8 AM and 9 AM at weeks 0, 2, 4, 6, and 8. Glucose dynamics were assessed by use of a combined IV glucose-insulin tolerance test (IVGITT) conducted before and at the end of the 8-week treatment period. Data for each combined IVGITT were interpreted by use of the minimal model. RESULTS: Plasma TG, TC, and VLDL concentrations significantly decreased over time in treated horses. At the completion of the 8-week treatment period, mean plasma VLDL concentration was 46% of the mean value for week 0 in treated horses. Insulin sensitivity significantly increased (> 2-fold) in treated horses, but glucose effectiveness and net insulin response were not affected. Levothyroxine sodium significantly increased the rate of insulin disposal. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-T4 decreases blood lipid concentrations, improves insulin sensitivity, and increases insulin disposal in horses. Levothyroxine sodium may have potential as a treatment for horses with reduced insulin sensitivity.

Animals↗
PubMed2005

Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses.

OBJECTIVE: To develop proxies calculated from basal plasma glucose and insulin concentrations that predict insulin sensitivity (SI; L.min(-1) x mU(-1)) and beta-cell responsiveness (ie, acute insulin response to glucose [AIRg]; mU/L x min(-1)) and to determine reference quintiles for these and minimal model variables. ANIMALS: 1 laminitic pony and 46 healthy horses. PROCEDURE: Basal plasma glucose (mg/dL) and insulin (mU/L) concentrations were determined from blood samples obtained between 8:00 AM and 9:00 AM. Minimal model results for 46 horses were compared by equivalence testing with proxies for screening SI and pancreatic beta-cell responsiveness in humans and with 2 new proxies for screening in horses (ie, reciprocal of the square root of insulin [RISQI] and modified insulin-to-glucose ratio [MIRG]). RESULTS: Best predictors of SI and AIRg were RISQI (r = 0.77) and MIRG (r = 0.75) as follows: SI = 7.93(RISQI) - 1.03 and AIRg = 70.1(MIRG) - 13.8, where RISQI equals plasma insulin concentration(-0.5) and MIRG equals [800 - 0.30(plasma insulin concentration 50)(2)]/(plasma glucose concentration - 30). Total predictive powers were 78% and 80% for RISQI and MIRG, respectively. Reference ranges and quintiles for a population of healthy horses were calculated nonparametrically. CONCLUSIONS AND CLINICAL RELEVANCE: Proxies for screening SI and pancreatic beta-cell responsiveness in horses from this study compared favorably with proxies used effectively for humans. Combined use of RISQI and MIRG will enable differentiation between compensated and uncompensated insulin resistance. The sample size of our study allowed for determination of sound reference range values and quintiles for healthy horses.

Animals↗
PubMed2003

Modifiable barriers to adherence to inhaled steroids among adults with asthma: it's not just black and white.

BACKGROUND: Sociobehavioral factors influence adherence to inhaled corticosteroid (ICS) in adults with asthma and warrant exploration as explanations of apparent racial disparities in adherence. OBJECTIVE: The purposes of this study were to identify barriers to adherence, potentially modifiable by healthcare providers, in a group of African Americans and non-African Americans and to test modifiable barriers as explanations of racial-ethnic differences in adherence. METHODS: We conducted a cohort study of 85 adults (mean age, 47 +/- 15 years; 61 [72%] female; 55 [65%] African American) with moderate or severe persistent asthma to determine modifiable sociobehavioral predictors of adherence. These were knowledge of the function of ICS, patient-perceived adequacy of communication with the provider, social support, attitude (perception of risks/benefits of ICS), depression, and self-efficacy. Adherence was calculated from electronic monitoring data as the mean of the number of doses recorded per 12 hours divided by the number prescribed, truncated at 100%. Past adherence, baseline severity of symptoms, and sociodemographics were treated as fixed confounders in ordinal logistic modeling. RESULTS: Adherence was 60% +/- 30%. In bivariate analyses, favorable attitude to ICS (P =.01) was associated with better adherence. Of immutable predictors, African American race-ethnicity (P =.001), lower educational achievement (P =.01), lower household income (P =.002), and more baseline symptoms (P =.003) were associated with poorer adherence. In multivariable analysis, controlling for immutable predictors, favorable attitude was associated with adherence. Favorable attitude was associated with greater adherence in African Americans and non-African Americans. Controlling for immutable factors, the race-adherence relationship was not mediated by the mutable factors, but economic factors (income and insurance) were mediators. CONCLUSION: Attitude is strongly related to adherence but does not mediate the effect of race-ethnicity.

Administration, Inhalation↗
PubMed2003

MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test.

The Bergman Minimal Model enables estimation of two key indices of glucose/insulin dynamics: glucose effectiveness and insulin sensitivity. In this paper we describe MINMOD Millennium, the latest Windows-based version of minimal model software. Extensive beta testing of MINMOD Millennium has shown that it is user-friendly, fully automatic, fast, accurate, reproducible, repeatable, and highly concordant with past versions of MINMOD. It has a simple interface, a comprehensive help system, an input file editor, a file converter, an intelligent processing kernel, and a file exporter. It provides publication-quality charts of glucose and insulin and a table of all minimal model parameters and their error estimates. In contrast to earlier versions of MINMOD and some other minimal model programs, Millennium provides identified estimates of insulin sensitivity and glucose effectiveness for almost every subject.

Blood Glucose↗
PubMed2002

Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis.

OBJECTIVE: To detect subclinical disseminated intravascular coagulation (DIC) in horses with colitis and to determine any association between the diagnosis of subclinical DIC and outcome or occurrence of complications in horses with colitis. DESIGN: Prospective study. ANIMALS: 37 horses admitted to a veterinary teaching hospital for treatment of acute colitis. PROCEDURE: Coagulation profiles were obtained on each horse 0, 24, and 48 hours after admission. Six tests were performed: platelet count, plasma fibrinogen concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and serum fibrin degradation products concentration. RESULTS: A clinicopathologic diagnosis of subclinical DIC was made if 3 of the 6 tests had abnormal results at any 1 sample period. No horse had clinical signs of DIC at the time of sampling. Twelve of 37 (32%) horses met the criteria for diagnosis of subclinical DIC within a 1-year period. Outcome was defined as survival or nonsurvival. Five of 12 horses with subclinical DIC and 2 of 25 horses without subclinical DIC did not survive. Crude odds ratio analysis revealed a horse with acute colitis was 8 times as likely to die or be euthanatized if a diagnosis of subclinical DIC was made. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicopathologic evidence of DIC is common and is significantly associated with a poor outcome in horses with acute colitis. Treatment of subclinical DIC may influence outcome in horses with acute colitis.

Acute Disease↗
PubMedDate not supplied

A comparison of ultra-high-molecular weight polyethylene cable and stainless steel wire using two fixation techniques for repair of equine midbody sesamoid fractures: an in vitro biomechanical study.

OBJECTIVE: To compare the monotonic tensile and fatigue strength of 16-gauge stainless steel wire (SSW) to ultra-high-molecular weight polyethylene (UHMWPE) cable using a transfixed cerclage technique in an in vitro midbody sesamoid osteotomy model. Endoscopic modifications to Martins transfixed cerclage technique were developed. A new suture technique of fixation was compared with the transfixed cerclage technique by measuring gap formation after cyclic testing. STUDY DESIGN: An in vitro biomechanical paired equine cadaver limb study. SAMPLE POPULATION: Twenty-one paired cadaveric adult equine forelimbs. METHODS: Uniaxial medial midbody sesamoid osteotomies were created in paired adult equine forelimbs. Monotonic tensile strength was measured on 10 forelimbs repaired by a transfixed cerclage technique using wire or cable. Fatigue testing to failure was performed on 4 forelimbs repaired using the transfixed cerclage technique by cycling the limbs between 500 N and 2,000 N. The limbs were initially repaired with wire, cycled until the wire broke, then repaired with cable and cycled again to failure. Fatigue testing for gap displacement was performed on 8 limbs repaired with either the transfixed cerclage technique or the suture technique. Limbs were cycled between 500 N and 2,000 N for 10,000 cycles. The limbs were repaired with wire initially, tested, and then repaired with cable and tested again. Twenty-two limbs were used for mechanical testing. The remaining limbs (20) were used to develop and practice the endoscopic transfixed cerclage (10 limbs) and suture (10 limbs) techniques. RESULTS: Ultimate tensile strength (UTS) of UHMWPE cable constructs was 34% greater than the UTS of SSW constructs. Fatigue strength was 2 to 20 times greater for UHMWPE cable constructs than SSW constructs. Separation of fragments was 153% less for limbs repaired by the suture technique compared with those repaired by the transfixed cerclage technique. CONCLUSIONS: UHMWPE cable shows promise for this clinical application because of its greater tensile and fatigue strength. The newly described suture technique significantly reduced gap formation compared with the transfixed cerclage technique. Osteotomy gap formation occurred early in cycling, suggesting that rigid support in the form of a cast may be needed during the early postoperative period for wiring techniques. CLINICAL RELEVANCE: Clinical testing of UHMWPE cable should eliminate problems of wire breakage seen with SSW. The endoscopic transfixed cerclage technique can be used by surgeons familiar with arthroscopic surgery. However, the suture technique needs to be tested in vivo to determine whether there is a clinical advantage compared with the transfixed cerclage technique.

Animals↗
PubMedDate not supplied

Uroperitoneum in 32 foals: influence of intravenous fluid therapy, infection, and sepsis.

Foals may present to a referral hospital with the primary diagnosis of uroperitoneum (UP), or they may develop UP while hospitalized for other reasons. Historical, physical, laboratory, and diagnostic variables of foals presenting with UP were compared to those developing UP while hospitalized. Emphasis was placed on the presence of electrolyte abnormalities, evidence of sepsis or infection, and development of anesthetic complications during surgical correction of the defect. Foals developing UP while in the hospital frequently had a history of dystocia and presented at a very young age (< 48 hours) with primary clinical signs compatible with intrauterine compromise or presumed hypoxic or ischemic insult with or without sepsis. Foals referred with suspected UP often had additional problems unrelated to the urinary system. These foals had hyponatremia and hyperkalemia on presentation, whereas foals receiving intravenous fluid therapy consisting of a balanced electrolyte solution did not develop the classical pattern of electrolyte abnormalities, yet a similar increase in serum creatinine and, frequently, decreasing urine production were noted. Infection was present in 63% of the foals, and 78% of foals revealed signs suggestive of sepsis or infection. Intrauterine compromise, presumed hypoxia or ischemia, and sepsis may predispose foals to development of UP. Anesthetic complications occurred in 16% of the foals undergoing surgical correction of the defect, although hyperkalemia was only present in half of the foals with anesthetic complications.

Aging↗