Ray C Boston

DairyNZ, Hamilton City, Waikato, New Zealand

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Publications (29)76.12 Total impact

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    ABSTRACT: The objective of this study was to develop a mathematical model that accurately describes the rise and decline in plasma progesterone concentrations, and is able to define parameters describing progesterone appearance and disappearance during the bovine oestrous cycle. Daily plasma progesterone data from 27 cows were used to develop a compartmental model consisting of an appearance function and an appearance modulating function. Model outputs included an apparent appearance or secretion duration, appearance rate and an average disappearance rate (expressed as arbitrary units per day; units/d). Shape-based clustering identified three common shape-based groups (or clusters) of progesterone profiles defined as either 'peaked' profile, with the profile reaching a distinguishable peak, 'structured', with the profile exhibiting a wave-like pattern, or 'flat top', with the profile reaching a plateau. Differences in the model parameters for the three different shapes of progesterone profiles were examined: peaked (n=13), flat top (n=7) and structured (n=7). The mean duration of apparent appearance was 11.49 (SD 0.17 d) for all 27 profiles. The model estimates for total appearance of progesterone (area under the curve; ng/ml per cycle), mean appearance rate and maximum appearance rate were 69.04 ng/ml per cycle (SD 15.2 ng/ml per cycle), 3.19 ng/ml per cycle (sd 0.7 ng/ml per d) and 6.70 ng/ml (SD 1.31 ng/ml), respectively. The average disappearance rate was 1.0 units/d (SD 0.04 units/d). The apparent appearance duration was greatest (P<0.01) in the flat top profiles (12.54, SD 0.41 d) followed by the structured (11.77, SD 0.66 d) and the peaked (10.80, SD 0.30 d) profiles. Total and mean progesterone appearance, maximum progesterone appearance rate, and the progesterone disappearance rates were not different between the profiles. The model successfully simulated all components of the progesterone profile and was able to define specific parameters of different shaped progesterone profiles. A simple model able to estimate parameters describing progesterone appearance and disappearance can be used to explore the relationships between profile shapes and reproductive outcomes.
    Journal of Dairy Research 05/2009; 76(2):249-56. · 1.34 Impact Factor
  • Ray C Boston, Dee Pei, Peter J Moate
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    ABSTRACT: Quantitative assessment of pancreatic insulin secretion rate in individuals may help advance our understanding and treatment of diabetes. We describe for the first time the application of a long-established numerical deconvolution procedure in which a prescribed input function is used to represent first-phase pancreatic secretion response to an intravenous glucose challenge (intravenous glucose tolerance test [IVGTT]) in individual subjects. We identify that C-peptide secretory response to an IVGTT can be described by a basal secretion rate (S(b)) (picomoles per liter per minute) and a first-phase secretory response characterized by a Gaussian function. The Gaussian function contains 3 parameters: P(1) (picomoles per liter per minute), which represents the peak rate secretion; P(2) (per square minute), which is related to the inverse of peak width at half-peak height; and P(3) (minutes), which is the time of the peak secretion rate. When applied to data from 8 healthy Chinese subjects, the estimated parameter values (mean +/- SD) were 19.2 +/- 12.9 pmol L(-1) min(-1), 1548 +/- 1143 pmol L(-1) min(-1), 1.09 +/- 1.21 min(-2), and 2.94 +/- 1.13 minutes for S(b), P(1), P(2), and P(3), respectively. The Gaussian input functions are shown to have similar shapes and to be highly concordant in magnitude with secretory responses estimated by means of the method of Eaton et al (1980) and by the ISEC computer program. In conclusion, we have presented a simple, integrated, validated, and easily implemented method suitable for quantifying pancreatic C-peptide and insulin secretion in individual human subjects. The superiority of our method in comparison with other methods is that it uses as an input function the Gaussian, which has been experimentally verified as describing in vivo the profile of pulsatile insulin secretion. The particular strength of our method is that the Gaussian parameters and simple indices derived from them provide a standardized and interpretable means for carrying out comparative investigations aimed at quantifying how pancreatic secretory responses to an IVGTT differ in various demographic groups or in response to therapeutic treatments.
    Metabolism: clinical and experimental 05/2009; 58(7):891-900. · 3.10 Impact Factor
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    ABSTRACT: To compare coagulation and platelet function parameters measured using a viscoelastic analyzer in 3 groups: foals presenting to a neonatal intensive care unit with presumed sepsis, normal foals, and adult horses. Preliminary prospective trial. Veterinary teaching hospital. Ten clinically healthy foals, 13 clinically healthy adult horses, and 17 foals sequentially admitted for suspected sepsis. Intervention- A single citrated (3.8%) blood sample collected at admission was submitted for coagulation evaluation using a viscoelastic analyzer. Time to initial clot formation (ACT), clot rate (CR), platelet function, and time to peak parameters were collected from the signature generated with the associated software. Peak clot strength was collected manually from signature tracings. Signalment, presenting complaint, blood culture results, clinical progression, and outcome were collected from the medical record. Kruskal-Wallis testing was used to determine differences in coagulation parameters between groups, as well as to identify any associations between coagulation variables, foal variables, and outcome. Normal foals were more likely to have increased platelet function (P=0.04) compared with normal adult horses. Prolonged ACT (P=0.004) and decreased CR (P=0.03) were associated with foals with positive blood culture. There was a trend toward prolonged ACT and increased likelihood of death (P=0.06). Healthy foals differ in values measured by the viscoelastic coagulation and platelet function analyzer compared with healthy adult horses. ACT and CR abnormalities were more likely to be observed in foals with positive blood cultures. The viscoelastic coagulation and platelet function analyzer may be useful in identifying early hemostasic and platelet dysfunction in critically ill foals, particularly those that are septic.
    Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001). 03/2009; 19(1):81-7.
  • Ray C Boston, Peter J Moate
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    ABSTRACT: The kinetics of nonesterified fatty acid (NEFA) metabolism in humans requires quantification to facilitate understanding of diseases like type 1 and 2 diabetes, metabolic syndrome, and obesity, and the mechanisms underpinning various interventions. Oral glucose tolerance tests (OGTT) and glucose meal tolerance tests (MTT) are potentially useful procedures for enabling quantification of NEFA kinetics because they both cause transitory, but substantial, declines and then rebounds in plasma NEFA concentrations in response to physiologically relevant increases in plasma glucose. The Boston MINIMAL model of NEFA kinetics was developed to analyze data from the intravenous glucose tolerance test (IVGTT), but in this work, we present for the first time its application to modeling NEFA data from both OGTT and MTT studies. This model enables estimation of SFFA (micromol.l(-1).min(-1)) (a parameter describing the maximum rate of lipolysis), and KFFA (%/min) (a parameter related to NEFA oxidation rate). The model could well describe the trajectories of NEFA concentrations following an OGTT (R2 in excess of 0.97) but was not as successful with the MTT (R2>0.65). Model parameters derived from analysis of OGTT and MTT data were well identified with coefficients of variation generally less than 15%. Type 2 diabetes, body mass index, and dietary treatment (high-fat vs. high-glycemic-index diets) were all shown to have significant effects on model parameters. Modeling plasma NEFA concentrations over 24 h has helped to identify and quantify the extent that periprandial NEFA peaks and nocturnal elevation in plasma NEFA can be accounted for by our model.
    AJP Regulatory Integrative and Comparative Physiology 06/2008; 295(2):R395-403. · 3.28 Impact Factor
  • Ray C Boston, Peter J Moate
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    ABSTRACT: Dynamics of nonesterified fatty acid (NEFA) metabolism in humans requires quantification if we are to understand the etiology of such diseases as type 1 and 2 diabetes, as well as metabolic syndrome and obesity, or if we are to elucidate the mechanism of action of various interventions. We present a new compartmental model that employs the pattern of plasma glucose concentrations in healthy young adults to predict dynamic changes that occur in plasma NEFA concentrations during either a glucose-only intravenous glucose tolerance test, or an insulin-modified intravenous tolerance test, or a modified protocol during which variable-rate glucose infusions were administered to prevent plasma glucose from declining below 100 mg/dl. The model described all of the major features of NEFA response to an intravenous glucose tolerance test, including an initial latency phase, a phase during which plasma NEFA concentrations plummet to a nadir, and a rebound phase during which plasma NEFA concentrations may rise to a plateau concentration, which may be substantially higher than the initial basal NEFA concentration. This model is consistent with physiological processes and provides seven adjustable parameters that can be used to quantify NEFA production (lipolysis) and utilization (oxidation). When tested on data from the scientific literature, the range in estimated rate of lipolysis was 24-36 micromol.l(-1).min(-1) and for NEFA oxidation rate was 25-54 micromol.l(-1).min(-1). All model parameters were well identified and had coefficients of variation < 15% of their estimated values. It is concluded that this model is suitable to describe NEFA kinetics in human subjects.
    AJP Regulatory Integrative and Comparative Physiology 05/2008; 294(4):R1140-7. · 3.28 Impact Factor
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    ABSTRACT: To identify risk factors for development of acute laminitis in horses during hospitalization for illness or injury. Retrospective case-control study. 73 horses that developed laminitis (case horses) and 146 horses that did not develop laminitis (control horses) during hospitalization. Case and control horses were matched in a 2:1 ratio by the date on which each horse was evaluated. Potential risk factors investigated included age, breed, and sex; highest and lowest values recorded during hospitalization for fibrinogen concentration, WBC count, PCV, and total solids concentration; and comorbid disease states, including pneumonia, endotoxemia, diarrhea, medically treated colic, surgically treated colic, pituitary adenoma, retained placenta or metritis, forelimb lameness, hind limb lameness, acute renal failure, and vascular abnormalities. A univariate screening of all potential risk factors was performed to determine which variables should be selected for further analysis. All factors found to be associated with development of laminitis were included in a multivariate conditional logistic regression model. Development of laminitis was marginally associated with lowest and highest fibrinogen concentrations, highest PCV, and lowest total solids concentration and significantly associated with pneumonia, endotoxemia, diarrhea, abdominal surgery for colic, and vascular abnormalities. In the multivariate analysis, only endotoxemia was significantly associated with laminitis. Endotoxemia is an important risk factor for development of acute laminitis in horses during hospitalization for medical or surgical conditions. Early recognition of endotoxemia, or the potential for it to develop in certain disease states, and initiation of treatment directed at endotoxemia or its consequences may help prevent laminitis in horses during hospitalization.
    Journal of the American Veterinary Medical Association 04/2007; 230(6):885-9. · 1.72 Impact Factor
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    ABSTRACT: Resumption of development by infective larvae (L3i) of parasitic nematodes upon entering a host is a critical first step in establishing a parasitic relationship with a definitive host. It is also considered equivalent to exit from the dauer stage by the free-living nematode Caenorhabditis elegans. Initiation of feeding, an early event in this process, is induced in vitro in L3i of Strongyloides stercoralis, a parasite of humans, other primates and dogs, by culturing the larvae in DMEM with 10% canine serum and 5mM glutathione at 37 degrees C with 5% CO(2). Based on the developmental neurobiology of C. elegans, resumption of development by S. stercoralis L3i should be mediated, in part at least, by neurons homologous to the ASJ pair of C. elegans. To test this hypothesis, the ASJ neurons in S. stercoralis first-stage larvae (L1) were ablated with a laser microbeam. This resulted in a statistically significant (33%) reduction in the number of L3i that resumed feeding in culture. In a second expanded investigation, the thermosensitive ALD neurons, along with the ASJ neurons, were ablated, but there was no further decrease in the initiation of feeding by these worms compared to those in which only the ASJ pair was ablated.
    Experimental Parasitology 02/2007; 115(1):92-7. · 2.15 Impact Factor
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    ABSTRACT: To compare the accuracy of a 3rd (Dolphin Voyager) versus 1st generation pulse oximeter (Nellcor N-180). Prospective laboratory investigation. Eight adult dogs. In anesthetized dogs, arterial oxygen saturation (SpO(2)) was recorded simultaneously with each pulse oximeter. The oxygen fraction in inspired gas (FiO(2)) was successively reduced from 1.00 to 0.09, with re-saturation (FiO(2) 0.40) after each breathe-down step. After each 3-minute FiO(2) plateau, SpO(2) and pulse rate (PR) were compared with the fractional arterial saturation (SaO(2)) and PR determined by co-oximetry and invasive blood pressure monitoring, respectively. Data analysis included Bland-Altman (B-A) plots, Lin's concordance correlation factor (rho(c)), and linear regression models. Over a SaO(2) range of 33-99%, the overall bias (mean SpO(2) - SaO(2)), precision (SD of bias), and accuracy (A(rms)) for the Dolphin Voyager and Nellcor N-180 were 4.3%, 4.4%, and 6.1%, and 3.2%, 3.0%, and 4.3%, respectively. Bias increased at SaO(2) < 90%, more so with the Dolphin Voyager (from 1.6% to 8.6%) than Nellcor N-180 (from 3.2% to 4.5%). The SpO(2) readings correlated significantly with SaO(2) for both the Dolphin Voyager (rho(c) = 0.94) and Nellcor N-180 (rho(c) = 0.97) (p < 0.001). Regarding PR, bias, precision, and accuracy (A(rms)) for the Dolphin Voyager and Nellcor N-180 were -0.5, 4.6, and 4.6 and 1.38, 4.3, and 4.5 beats minute(-1), respectively. Significant correlation existed between pulse oximeter and directly measured PR (Dolphin Voyager: rho(c) = 0.98; Nellcor N-180: rho(c) = 0.99) (p < 0.001). In anesthetized dogs with adequate hemodynamic function, both instruments record SaO(2) relatively accurately over a wide range of normal saturation values. However, there is an increasing overestimation at SaO(2) < 90%, particularly with the Dolphin Voyager, indicating that 3rd generation pulse oximeters may not perform better than older instruments. The 5.4-fold increase in bias with the Dolphin Voyager at SaO(2) < 90% stresses the importance of a 93-94% SpO(2) threshold to ensure an arterial saturation of >or=90%. In contrast, PR monitoring with both devices is very reliable.
    Veterinary Anaesthesia and Analgesia 09/2006; 33(5):281-95. · 1.34 Impact Factor
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    ABSTRACT: 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. 6 Thoroughbreds. 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. 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). 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.
    American Journal of Veterinary Research 05/2006; 67(4):654-62. · 1.35 Impact Factor
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    ABSTRACT: 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. 1 laminitic pony and 46 healthy horses. 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]). 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. 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.
    American Journal of Veterinary Research 01/2006; 66(12):2114-21. · 1.35 Impact Factor
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    ABSTRACT: Objective: To identify and describe the physical, historical, and clinicopathologic characteristics of diseases requiring emergency treatment in postpartum mares, and to evaluate the utility of these characteristics in making an accurate diagnosis in these mares.Design: Retrospective study.Setting: University large animal hospital.Animals: One hundred and sixty-three mares admitted for emergency treatment within 30 days following parturition between the years 1992 and 2002.Interventions: None.Measurements and main results: Information obtained from the medical records included age, breed, date of admission, sex of the foal from this parturition, time from parturition to admission, duration of clinical signs prior to admission, and any report of dystocia or normal attended delivery, physical examination and clinicopathologic findings and diagnosis. Urogenital hemorrhage and large colon volvulus were the most common diagnoses, comprising 16.6% and 15.9% of total cases, respectively. Older mares were more likely to have a diagnosis of urogenital hemorrhage than younger mares. Mares with urogenital hemorrhage had a median age of 13 years and were admitted to the hospital significantly closer to parturition than mares with other diagnoses. Anemia, hypoproteinemia, and hypofibrinogenemia were significantly associated with a diagnosis of urogenital hemorrhage and occurred in 32%, 36%, and 26% of the mares with urogenital hemorrhage, respectively. Dystocia was more commonly reported (70%) in mares with metritis. Leukopenia was more common (88%) in mares with uterine tears.Conclusions: Careful evaluation of clinicopathologic data can aid the emergency clinician in making a correct diagnosis in postpartum mares with emergent problems.
    Journal of Veterinary Emergency and Critical Care. 08/2005; 15(3):193 - 200.
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    ABSTRACT: To evaluate glucose and lipid metabolism in healthy adult horses administered levothyroxine sodium (L-T4). 12 healthy adult mares. 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. 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. 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.
    American Journal of Veterinary Research 07/2005; 66(6):1032-8. · 1.35 Impact Factor
  • Journal of the American Veterinary Medical Association 06/2005; 226(9):1476. · 1.72 Impact Factor
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    ABSTRACT: The morbidity and mortality associated with asthma are suspected to be a result, in part, of poor adherence to inhaled corticosteroid regimens. One influence on adherence may be the perception of symptoms. Because symptoms and adherence affect each other over time, a conventional statistical approach for studying these relationships may provide biased results. To understand the influence of previous asthma symptoms and previous adherence on current symptoms. A total of 76 adults, mean age 48 years +/- 15 years, with moderate or severe persistent asthma underwent 6 weeks of electronic monitoring of their use of inhaled corticosteroids and completed a daily symptom diary. We estimated the effect of earlier adherence on final symptoms by using marginal structural models, estimated by using a weighted estimation technique. Morning was better than evening adherence, which declined over the observation period. The variability of adherence appeared to increase over the observation period. In addition, earlier adherence predicted current adherence more strongly than earlier symptoms predicted current adherence. There was no overall significant relationship between cumulative adherence and final symptoms. These data indicate that accurately determining past adherence will help identify patients to target to improve their future adherence. These analyses are important for understanding time-varying measures in the clinical setting.
    Journal of Allergy and Clinical Immunology 05/2005; 115(4):810-4. · 12.05 Impact Factor
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    ABSTRACT: To establish the pharmacokinetics of stavudine within the cerebrospinal fluid (CSF) of patients infected with human immunodeficiency virus (HIV). Pharmacokinetic study. General clinical research center. Thirty-six patients infected with HIV; 21 were receiving long-term stavudine therapy, 15 were not (single-dose treatment group). 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. 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. 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.
    Pharmacotherapy 02/2005; 25(1):10-7. · 2.31 Impact Factor
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    ABSTRACT: 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.
    Journal of Veterinary Internal Medicine 01/2005; 19(6):889-93. · 2.06 Impact Factor
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    ABSTRACT: The purpose of this research was to determine inter- and intrapatient differences in the pharmacokinetic profiles of etoposide and its genotoxic catechol metabolite during conventional multiple-day dosing of etoposide in pediatric patients. Seven pediatric patients with various malignancies received etoposide at a dose of 100 mg/m(2) i.v. over 1 h daily for 5 days. Blood samples were taken at selected time points on days 1 and 5. Plasma and protein-free plasma concentrations of etoposide and etoposide catechol were determined using a validated liquid chromatography/tandem mass spectrometry assay. Pharmacokinetic parameters of both etoposide and etoposide catechol were calculated using the WinSAAM modeling program developed at NIH. The mean maximum concentration (C(max)) for total (0.262 +/- 0.107 micro g/ml) and free catechol (0.0186 +/- 0.0082 micro g/ml) on day 5 were higher than the mean C(max) for total (0.114 +/- 0.028 micro g/ml) and free catechol (0.0120 +/- 0.0091 micro g/ml) on day 1. The mean area under the plasma concentration-time curve (AUC)(24h) for total (105.4 +/- 49.1 micro g.min/ml) and free catechol (4.89 +/- 2.23 micro g x min/ml) on day 5 were much greater (P < 0.05) than those for total (55.9 +/- 16.1 micro g x min/ml) and free catechol (3.04 +/- 1.04 micro g x min/ml) on day 1. In contrast, the AUC(24h) for etoposide was slightly lower on day 5 than on day 1. The C(max) and AUC(24h) for etoposide catechol were significantly higher on day 5 than on day 1. This suggests that metabolism of etoposide to its catechol metabolite increases in pediatric patients receiving multiple-day bolus etoposide infusions. These findings may be relevant to future reduction of the risk of leukemia as a treatment complication, because etoposide and etoposide catechol are both genotoxins.
    Clinical Cancer Research 06/2004; 10(9):2977-85. · 7.84 Impact Factor
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    ABSTRACT: Objective: The objective of this study was to evaluate coagulation profiles in horses with surgical treatment of large colon volvulus (LCV), and determine if an association exists between hemostatic dysfunction and outcome.Design: Prospective clinical investigation from February to December 2000.Setting: Large animal intensive care unit in a veterinary teaching hospital.Interventions: Blood was collected from horses intra-operatively, 24, and 48 hours following surgical treatment for LCV.Measurements: Coagulation profiles, thrombin–antithrombin (TAT) levels, and D-dimer concentrations were determined for each time point. The number of tests abnormal in the standard coagulation profile, defined as the degree of hemostatic dysfunction, was determined for each horse for the duration of the study period. The association between each test and outcome, as well as the degree of hemostatic dysfunction for each horse and outcome, was determined using univariate analysis and logistic regression. TAT levels and D-dimer concentrations were compared to the results of the standard coagulation profile and to patient outcome using univariate analysis and logistic regression.Main results: Seventy percent of horses evaluated with surgical treatment of LCV had evidence of hemostatic dysfunction (3/6 tests abnormal). Only 18% of those patients had clinical signs recognized by the attending clinician as a coagulopathy. There was an association between the development of a coagulopathy and outcome, with horses with 4/6 tests abnormal being more likely to be euthanized, and those with 3/6 tests abnormal having a prolonged hospital stay. Platelet count, prothrombin time, and TAT levels may be helpful in predicting outcome in horses with LCV.Conclusions: Hemostatic function should be evaluated in horses with surgical treatment of LCV to detect subclinical coagulopathies and direct subsequent intervention.
    Journal of Veterinary Emergency and Critical Care. 12/2003; 13(4):215 - 225.
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    ABSTRACT: Sociobehavioral factors influence adherence to inhaled corticosteroid (ICS) in adults with asthma and warrant exploration as explanations of apparent racial disparities in adherence. 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. 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. 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. Attitude is strongly related to adherence but does not mediate the effect of race-ethnicity.
    Journal of Allergy and Clinical Immunology 07/2003; 111(6):1219-26. · 12.05 Impact Factor
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    ABSTRACT: 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.
    Diabetes Technology &amp Therapeutics 02/2003; 5(6):1003-15. · 2.21 Impact Factor