[show abstract][hide abstract] ABSTRACT: Little information is available on normal ruminal pH values for domestic sheep (Ovis aries) housed in a research setting and fed a complete pelleted ration. Sheep maintained on pelleted diets undergoing surgical procedures often present with postoperative anorexia and rumen atony. To determine the relationship between diet and postoperative rumen acidosis and associated atony, we studied dietary effects on ruminal pH in an ovine surgical model. Sheep undergoing orthopedic surgical procedures were randomized into 2 diet groups. Group 1 (n = 6) was fed complete pelleted diet during the pre- and postoperative period, and group 2 (n = 6) was fed timothy grass hay exclusively throughout the study. Measures included ruminal pH, ruminal motility, and rate of feed refusal, which was monitored throughout the pre- and postoperative periods. The 2 groups did not differ significantly before surgery, and the ruminal parameters remained largely within normal limits. However, a downward trend in the strength and frequency of rumen contractions was observed in pellet-fed sheep. After surgery, the pellet-fed group showed clinical signs consistent with ruminal acidosis, supported by decreased ruminal motility, anorexia, putrid-smelling ruminal material, and death of ruminal protozoa. Intervention by transfaunation in clinically affected sheep resulted in resolution of signs. Our findings suggest that sheep fed grass hay appear to have a more stable ruminal pH, are less likely to experience anorexia and rumen atony, and thereby exhibit fewer postoperative gastrointestinal complications than do sheep on a pellet diet.
Journal of the American Association for Laboratory Animal Science: JAALAS 01/2011; 50(1):27-32. · 1.15 Impact Factor
[show abstract][hide abstract] 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. · 2.59 Impact Factor
[show abstract][hide abstract] 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.
[show abstract][hide abstract] 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.
[show abstract][hide abstract] 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.
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
[show abstract][hide abstract] 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
[show abstract][hide abstract] ABSTRACT: To determine the history, clinicopathologic findings, and results of surgery for effusive-constrictive pericarditis associated with Coccidioides immitis infection in dogs.
17 client-owned dogs that underwent a subtotal pericardectomy and epicardial excision.
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.
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%.
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.
Journal of the American Veterinary Medical Association 09/2005; 227(3):435-40. · 1.72 Impact Factor
[show abstract][hide abstract] 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
[show abstract][hide abstract] ABSTRACT: To establish the pharmacokinetics of stavudine within the cerebrospinal fluid (CSF) of patients infected with human immunodeficiency virus (HIV).
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.
[show abstract][hide abstract] 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
[show abstract][hide abstract] 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
[show abstract][hide abstract] ABSTRACT: STATA is a statistical analysis program developed by STATA Corporation, College Station, TX. In addition to supporting a very
extensive array of statistical tools, STATA incorporates a critical complement of data management and graphics facilities
as well. As demonstrated in another article in this volume (Boston et al., 2002), STATA fits very well into the kinetic analysis
suite of tools. In that paper, we show how some preliminary analyses of intravenous tolerance test (IVGTT) data leading to
estimates of key parameters and their errors in the minimal model (see Bergman and Bowden, 1981) could easily be performed
with STATA. We also demonstrate the transfer of some WinSAAM Population Management Results from WinSAAM to STATA for further
appraisal as well as for graphical display. Here we will present aspects of the organization, operation, use, and availability
Advances in experimental medicine and biology 02/2003; 537:353-69. · 1.83 Impact Factor
[show abstract][hide abstract] 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.
[show abstract][hide abstract] ABSTRACT: 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.
37 horses admitted to a veterinary teaching hospital for treatment of acute colitis.
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.
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.
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.
Journal of the American Veterinary Medical Association 05/2002; 220(7):1034-8. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
An in vitro biomechanical paired equine cadaver limb study.
Twenty-one paired cadaveric adult equine forelimbs.
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.
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.
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 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.
Veterinary Surgery 01/2002; 31(5):445-54. · 1.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: ABSTRACT 1 2 The dynamics ,of non-esterified fatty ,acid (NEFA) metabolism ,in humans ,requires 3 quantification if we ,are to understand ,the etiology of such ,diseases as type ,1 and ,2 4 diabetes as well as metabolic syndrome and obesity, or if we are to elucidate the 5 mechanism,of action ,of various ,interventions. We present ,a new ,compartmental ,model 6 that employs the pattern of plasma glucose concentrations in healthy young adults, to 7 predict the dynamic,changes that occur in plasma,NEFA concentrations during either a 8 glucose only intravenous glucose tolerance test (GO-FSIGT), or an insulin modified 9 intravenous tolerance test (IM-FSIGT) or a ,modified ,protocol (IM-FSIGT-CLAMP) 10 during which ,variable rate glucose ,infusions were ,administered ,to prevent ,plasma 11 glucose from declining below 100 mg/dl. The model,described all of the major features 12 ofthe NEFA response to an IVGTT including, an initial latency phase, a phase during 13 which plasma NEFA concentrations plummet to a nadir, and a rebound phase during 14 which plasma NEFA concentrations may ,rise to a ,plateau concentration which may ,be 15