Growth deceleration and restoration after serious burn injury.

There is a common perception that burned children are at risk for growth deceleration. However, because the prevalence, duration, and degree of this stereotypic growth are poorly described, making informed decisions about treatment is difficult. This article describes the natural history of growth after burn injury, according to the findings of a retrospective review conducted in a regional pediatric burn center. The study population comprised children younger than 13 years at the time of injury, who survived burns involving >or=30% TBSA. Main outcome measures were height and weight; values obtained upon admission for burn injury and at all subsequent hospital admissions were converted to height-for-age and weight-for-age Z scores with use of a reference standard. Z scores were then used to determine whether baseline height and weight status (according to initial admission data) were recouped after burn injury. Medical records of 159 patients (2910 admissions) were reviewed. Children with massive burns (>or=50% TBSA) had height-for-age Z scores that were significantly below their baseline average for all years studied (mean fall in Z score units of 0.50-0.76; P < .0001). This decline in height-for-age Z scores represented a deficit of 1.6 to 5.8 cm. Seventeen patients (11%) had height-for-age Z scores consistent with stunting. Weight-for-age Z scores were not statistically lower than the reference standard, except for patients with massive burns up to 1.5 years post-burn. In our population of burned children, only massively burned children demonstrated a decline in stature. The decline for most was modest.

Factors determining access to surgery for children with congenital cardiac disease in Guatemala, Central America.

BACKGROUND: Surgical intervention for children with congenital cardiac disease in the developing world often occurs late. Our objective was to identify factors that placed Guatemalan children at risk for delayed care. METHODS: We investigated the medical and socioeconomic background of 178 children under the age of 18 years who received their first corrective surgery for congenital cardiac disease at the Unidad de Cirugía Cardiovascular de Guatemala in 2002. A retrospective review of medical records was performed. Each case was stratified into one of three surgical classes based upon customary practice in the United States of America. The outcome we measured was age at surgery, adjusting for the surgical class. Logistic regression was performed and odds ratios calculated. RESULTS: In univariate analyses, patients presented later for surgery if they were from rural areas (p equals 0.001), did not have social security membership (p equals 0.004), or paid any amount towards the cost of their surgery (p less than 0.001). Age at surgery was also positively correlated with the distance of the home of the patient from the surgical centre (p equals 0.002). For the subset of patients who applied for financial assistance, we found that children presented later for surgery if they required institutional support (p equals 0.001), or came from households of larger size (p less than 0.001). CONCLUSIONS: Guatemalan children with congenital cardiac disease may be at risk for delayed surgical care if they come from rural areas, areas distant from the surgical centre, or from families without membership of social security.

Relationship of pancreatic duct dilation to age and clinical findings in cats.

Dilation of the pancreatic duct has been described as an ultrasonographic feature of pancreatitis in cats. The purpose of this study was to determine normal pancreatic duct width in healthy older cats and assess the significance of pancreatic duct dilation observed in a clinical population. In a prospective study, pancreatic ultrasound was performed in 15 healthy cats (mean age 13 +/- 3 years). Mean pancreatic width of left lobe, body, and right lobe was 0.65 +/- 0.16 cm (0.46-1.03 cm), 0.64 +/- 0.14 cm (0.46-0.9 cm), and 0.43 +/- 0.09 cm (0.3-0.57 cm), respectively. Mean pancreatic duct width was 0.13 +/- 0.04 cm (0.06-0.24 cm), which was significantly larger than previously reported for younger cats (0.08 +/- 0.025 cm) (P < 0.001). One hundred and four of 1445 clinical patients (7.2%) were diagnosed with a dilated pancreatic duct and were reviewed in a retrospective study. Incidence of pancreatic duct dilation was significantly higher in older than in younger cats (2.7% in cats < 1-5 years vs. 18.1% in cats 15 years or older; P < 0.001). Mean pancreatic duct width was 0.23 +/- 0.07 cm (0.14-0.52 cm), and there was a significant correlation between age and pancreatic duct width (P = 0.01). There was also a significant relationship between the mean ratio of pancreatic duct width and pancreatic thickness (n = 98) (0.29 +/- 0.09; 0.09-0.58; P = 0.041). There was no significant difference in age between cats with and without pancreatic disease. There was no association between pancreatic disease and pancreatic duct width or pancreatic duct width/pancreatic thickness ratio. Pancreatic duct width and pancreatic duct width/pancreatic thickness ratio in cats are significantly associated with age.

Quantitative evaluation of bone density using the Hounsfield index.

PURPOSE: The primary aims of this retrospective study were to: (1) evaluate bone quality in different segments of the edentulous jaw and correlate it with demographic data and (2) establish a quantitative and objective assessment of bone quality based on the Hounsfield scale. MATERIALS AND METHODS: One hundred one randomly selected computerized tomographic (CT) scans were used for the analysis. Edentulous segments ranging from 10 to 30 mm were selected for evaluation, and the findings were analyzed and correlated to demographics. Implant recipient sites were evaluated visually for bone classification by 2 independent examiners. The same sites were subsequently evaluated digitally using the Hounsfield scale, and the results were correlated with the visual classification. RESULTS: The 4 quadrants of the mouth displayed Hounsfield unit (HU) values ranging from -240 HU to 1,159 HU. The highest unit/mean density value (559 +/- 208 HU) was found in the anterior mandible, followed by 517 +/- 177 HU for the anterior maxilla, 333 +/- 199 HU for the posterior maxilla, and 321 +/- 132 HU for the posterior mandible. There was no association between the Hounsfield value and density and age or gender. When subjective bone quality was correlated to Hounsfield index findings, only the relationship between HU and type 4 bone was found to be significant. CONCLUSIONS: Knowledge of the Hounsfield value as a quantitative measurement of bone density can be helpful as a diagnostic tool. It can provide the implant surgeon with an objective assessment of bone density, which could result in modification of surgical techniques or extended healing time, especially in situations where poor bone quality is suspected.

Differential effects of central leptin, insulin, or glucose administration during fasting on the hypothalamic-pituitary-thyroid axis and feeding-related neurons in the arcuate nucleus.

The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and alpha-MSH/cocaine and amphetamine-regulated transcript. Because the central administration of leptin is capable of preventing the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous administration of 30 mU/d insulin or 648 microg/d glucose into the cerebrospinal fluid by osmotic minipump might also have similar effects on the hypothalamic-pituitary-thyroid axis. As anticipated, the intracerebroventricular infusion of leptin reduced fasting-induced elevations in NPY and AGRP mRNA and increased proopiomelanocortin and cocaine and amphetamine-regulated transcript mRNA in the arcuate nucleus. In addition, leptin prevented fasting-induced reduction in pro-TRH mRNA levels in the paraventricular nucleus and in circulating thyroid hormone levels. In contrast, whereas insulin increased proopiomelanocortin mRNA and both insulin and glucose reduced NPY mRNA in arcuate nucleus neurons, neither prevented the fasting-induced suppression in hypophysiotropic TRH mRNA or circulating thyroid hormone levels. We conclude that insulin and glucose only partially replicate the central effects of leptin and may not be essential components of the hypothalamic-pituitary-thyroid regulatory system during fasting.

Gender-based differences in brachial artery flow-mediated vasodilation as an indicator of significant coronary artery disease.

Ultrasound of the brachial artery is widely used to assess endothelial function, but whether brachial artery flow-mediated vasodilation (FMD) differs between women and men who have coronary artery disease (CAD) has not been examined. To investigate gender-based differences in brachial artery FMD as an indicator of significant CAD, FMD was measured in women and men outpatients who had CAD (coronary stenosis >50%, n = 64) and those who did not have significant CAD (n = 145). FMD in women who had CAD (n = 33, 9.1 +/- 0.8%) was higher than that in similarly aged men who had CAD (n = 31, 6.4 +/- 0.5%; p = 0.008). The FMD cutpoint that maximized sensitivity with least effect on specificity for screening CAD was 15% (91% sensitivity, 25% specificity) in women but 10% (90% sensitivity, 43% specificity) in men. If the cutpoint as defined in men were used to evaluate women, brachial artery ultrasound would fail to diagnose 42% of women who do not have significant CAD; thus, a higher FMD cutpoint is required to optimize the sensitivity of FMD for identifying women who have significant CAD compared with similarly aged men. In studies using FMD to evaluate cardiovascular risk, different standards should be applied for women and men.

Peripheral vascular endothelial function correlates with exercise capacity in women.

BACKGROUND: Vascular endothelial function has been observed to correlate with exercise capacity in predominantly male populations. Gender-based differences exist in the clinical course of coronary artery disease, and previous studies indicate that estrogen may influence endothelial function. These observations raise the possibility that the relationship between endothelial function and exercise capacity in women may differ from that in men. HYPOTHESIS: This study aimed to determine whether peripheral vascular endothelial function correlates with exercise capacity in women. METHODS: Women who were referred for clinically indicated exercise testing with technetium-99 myocardial perfusion imaging were consecutively recruited. To ensure a population free of exercise limitation due to ischemic heart disease, women without myocardial perfusion defects were included for analysis in this study (n = 105). Endothelial function was assessed by brachial artery ultrasound flow-mediated vasodilation (FMD). Exercise capacity was defined as the duration of exercise on a symptom-limited Bruce protocol. RESULTS: Mean FMD was 11.8 +/- 0.6%, and median FMD was 12%. Subjects with an FMD less than the median of 12% had a significantly shorter exercise time than those with FMD > or = 12% (411 +/- 17 vs. 482 +/- 24 s, p = 0.014). There was a significant correlation between FMD and exercise time (r = 0.34, p < 0.001). Age and body mass index were additional predictors of exercise time; however, the relationship between FMD and exercise time was independent of these variables. CONCLUSION: Brachial artery FMD correlates with exercise capacity in women, even in the absence of ischemic heart disease.

Childhood overweight and maturational timing in the development of adult overweight and fatness: the Newton Girls Study and its follow-up.

OBJECTIVE: Although several studies have suggested that early menarche is associated with the development of adult overweight, few have accounted for childhood overweight before menarche. STUDY DESIGN: A 30-year follow-up of the original participants in the Newton Girls Study, a prospective study of development in a cohort of girls followed through menarche, provided data on premenarcheal relative weight and overweight (BMI >85th percentile), prospectively obtained age at menarche, self-reported adult BMI, overweight (BMI > 25), obesity (BMI > 30) and, for a subset of participants, percentage body fat by dual-energy x-ray absorptiometry. RESULTS: Of the 448 women who participated in the adult follow-up at a mean age of 42.1 years (SD: 0.76 years), 307 had childhood data with which to characterize premenarcheal and menarcheal weight status and age at menarche. After a follow-up of 30.1 years (SD: 1.4 years), reported BMI was 23.4 (4.8), 28% were overweight, and 9% were obese. In multivariate linear and logistic-regression analyses, almost all of the influence on adult weight status was a result of premenarcheal weight status (model R2 = 0.199). Inclusion of a variable to reflect menarcheal timing provided very little additional information (model R2 = 0.208). Girls who were overweight before menarche were 7.7 times more likely to be overweight as adults (95% confidence interval: 2.3, 25.8), whereas early menarche (at < or = 12 years of age) did not elevate risk (odds ratio: 1.3, 95% confidence interval: 0.66, 2.43). A similar pattern of results was observed when percentage body fat in adulthood was evaluated. CONCLUSIONS: The apparent influence of early maturation on adult female overweight is largely a result of the influence of elevated relative weight on early maturation. Interventions to prevent and treat overweight should focus on girls before they begin puberty.

Quantitative echocardiographic [corrected] evaluation of mitral endocardiosis in dogs using ratio indices.

This study compares M-mode echocardiographic ratio indices (ERIs) in dogs with mitral regurgitation due to chronic valvular disease (CVD/MR) for their ability to discriminate and quantify associated echocardiographic changes. Weight-based M-mode ERIs were determined retrospectively for 2 groups of dogs, normal (n = 47) and CVD/MR (n = 176). The CVD/MR group was further subdivided into those with (CVD/MR B, n = 74) and without (CVD/MR A, n = 102) left-sided congestive heart failure (LCHF). ERIs were compared descriptively (summary statistics) and also by receiver-operator characteristic curve areas (ROCAs) for their ability to discriminate between groups. Univariate logistic regression (LR) models were used to estimate the odds ratio for each ERI as a predictor of the CVD/MR condition as well as to predict LCHF within the CVD/MR group. A novel ERI (wdeltaA), designed to express body size-normalized short-axis stroke area, was sensitive (90%) and specific (98%) to discriminate between normal and CVD/MR at a cutoff value of 1.8 standard deviations (wdeltaA = 2.1). Prediction of LCHF within the CVD/MR group was more problematic, but an ERI expressing left atrial size (wLA) showed 76% sensitivity and 81% specificity at a cutoff value of 5.2 standard deviations (wLA = 1.55). Ours was a descriptive study of echocardiographic patterns of pathology associated with CVD/ MR and determined which ERIs are sensitive and specific for CVD/MR and for LCHE ERIs normalize echocardiographic data for body size in dogs and are well-suited to quantitative descriptions and analysis.

EBV and systemic lupus erythematosus: a new perspective.

We have proposed that EBV uses mature B cell biology to access memory B cells as a site of persistent infection. A central feature of this model is that EBV adapts its gene expression profile to the state of the B cell it resides in and that the level of infection is stable over time. This led us to question whether changes in the behavior or regulation of mature B cells would alter the state of EBV persistence. To investigate this, we studied the impact of systemic lupus erythematosus (SLE), a disease characterized by immune dysfunction, on EBV infection. We show that patients with SLE have abnormally high frequencies of EBV-infected cells in their blood, and this is associated with the occurrence of SLE disease flares. Although patients with SLE have frequencies of infected cells comparable to those seen in immunosuppressed patients, in SLE the effect was independent of immunosuppressive therapy. Aberrant expression of viral lytic (BZLF1) and latency (latency membrane proteins 1 and 2a) genes was also detected in the blood of SLE patients. We conclude that the abnormal regulation of EBV infection in SLE patients reflects the sensitivity of the virus to perturbation of the immune system.

Gender-specific patterns of left ventricular and myocyte remodeling following myocardial infarction in mice deficient in the angiotensin II type 1a receptor.

Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explore the specific role for activation of the AT 1a R subtype in post-MI remodeling and whether gender differences exist in the patterns of remodeling in wild-type and AT 1a R knockout (KO) mice. AT 1a R-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and AT 1a R-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the AT 1a R-KO mice compared with wild-type mice. Male and female wild-type and male AT 1a R-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female AT 1a R-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female AT 1a R-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted AT 1a R gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the AT 1a R. Further work is necessary to explore the potential mechanisms underlying these gender-based differences.

Ascending brainstem pathways are not involved in lipopolysaccharide-induced suppression of thyrotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus.

The nonthyroidal illness syndrome associated with fasting, infection, and chronic illness is characterized by low thyroid hormone levels and low or inappropriately normal TSH levels in circulating blood and reduced synthesis of TRH in hypophysiotropic neurons residing in the hypothalamic paraventricular nucleus (PVN). To test the hypothesis that ascending brainstem pathways are involved in mediation of bacterial lipopolysaccharide (LPS)-induced suppression of TRH mRNA in the PVN, we unilaterally transected brainstem pathways to the PVN and determined the effects of LPS on TRH gene expression and, as a control, on CRH gene expression in hypophysiotropic neurons using semiquantitative in situ hybridization histochemistry. The efficacy of the transection was determined by immunocytochemical detection of ascending adrenergic pathways in the PVN. In vehicle-treated animals, CRH mRNA in the PVN showed a significant reduction on the transected side compared with the intact side, whereas a significant increase in TRH mRNA was observed on the transected side compared with the intact side. After LPS administration (250 microg/100 g body weight), a dramatic increase in CRH mRNA was observed on the intact side, and a significantly lesser increase was found on the transected side. In contrast, LPS treatment resulted in reduction in TRH mRNA on the transected side compared with the intact side and a significant reduction in TRH mRNA on the transected side compared with vehicle-treated animals. These studies confirm an important role of ascending brainstem projections in LPS-induced activation of CRH gene expression, but indicate that they do not mediate the effect of LPS to inhibit hypophysiotropic TRH gene expression.

Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse.

Agouti-related protein (AGRP) is thought to be one of the neuropeptides mediating the effects of leptin on appetite and satiety. The central administration of AGRP not only stimulates food intake, but also inhibits the hypothalamic-pituitary-thyroid axis (HPT) axis, closely replicating the central hypothyroid state induced by fasting. AGRP binds as an endogenous antagonist or inverse agonist of the central melanocortin receptors but has also been hypothesized to have melanocortin receptor-independent effects. Thus, we determined whether the central effects of AGRP on the HPT axis are altered in mice with selective deletion of the melanocortin 4 receptor (MC4-R). AGRP or artificial cerebrospinal fluid was administered daily into the lateral ventricle of adult, male MC4-R knockout and wild-type (WT) mice for 3 d. AGRP significantly increased the cumulative food intake and weight of white and brown adipose tissue, suppressed circulating levels of T(4) [control vs. AGRP in WT (microg/dl): 4.54 +/- 0.16 vs. 3.87 +/- 21], and inhibited proTRH mRNA content in the hypothalamic paraventricular nucleus of WT mice (control vs. AGRP in WT (density units +/- sem): 4.65 +/- 0.50 vs. 2.47 +/- 0.17). In contrast, no significant effects of AGRP were observed in any of these parameters in the MC4-R knockout mice. These data suggest that AGRP signaling to TRH hypophysiotropic neurons in the paraventricular nucleus is primarily mediated by the MC4-R and therefore, binding to the MC3-R or other putative AGRP receptors may have only a minor role.

Variability in planning and assessment: statistical considerations and models.

Nutrition researchers are called upon to inform policymakers of the consequences of consuming different amounts of various nutrients: how much is enough, how much is too much, and why. Traditionally, requirements were described by population-average levels and some measure of between-individual variation, whereas toxicities were described by single levels above which a toxic response was likely to occur. These statistics were used to estimate the prevalence of various adverse health effects in individual populations. Recently, accumulated data and improved understanding have led to more complete descriptions of the utilization of a few important nutrients and to the formulation of a model that includes both requirement and toxicity as extremes of the healthy-intake spectrum. This approach is based on estimating the full statistical distributions of individual nutritional deficits and surfeits within a population and using this to derive prevalence curves for specific adverse health effects. This information promises to provide policy planners with better tools to judge the health of populations, design feeding programs, and predict the sequelae of modifications in food supply and dietary habits.

Chronicle of the Institute of Medicine physical activity recommendation: how a physical activity recommendation came to be among dietary recommendations.

Under a contract from the US Department of Health and Human Services, a multidisciplinary expert panel was appointed to review "the scientific literature regarding macronutrients and energy and develop estimates of daily intake that are compatible with good nutrition throughout the life span and that may decrease the risk of chronic disease." Within the overall context of the charge, the panel sought to quantify rates and components of daily energy expenditure in healthy adults with body mass indexes (in kg/m(2)) of 18.5-25, in growing children (in the 5th-85th percentiles of weight-for-length), and in pregnant and lactating women. The recommendation for adults became the daily energy intake necessary to cover total daily energy expenditure (TEE). For special cases, dietary macronutrients and energy to support child growth and pregnancy and lactation by women were considered. TEE was based on the results of doubly labeled water studies, and the TEE results were presented in units of physical activity level (PAL = TEE/BEE) and DeltaPAL, where BEE is the basal rate of energy expenditure extrapolated to 24 h. Most adults (66%) maintaining a BMI in the healthful range had PAL values >1.6, or the equivalent of > or =60 min of physical activity of moderate intensity each day. Hence, on the basis of the doubly labeled water data and the results of epidemiologic studies, the physical activity recommendation for adults was judged to be 60 min/d. The recommendation for children was for a minimum of 60 min/d. In conclusion, dietary and physical activity recommendations for healthful living are inextricably intertwined. Adequate physical activity provides protection against chronic diseases and helps to balance energy expenditure and intake.

Cocaine- and amphetamine-regulated transcript co-contained in thyrotropin-releasing hormone (TRH) neurons of the hypothalamic paraventricular nucleus modulates TRH-induced prolactin secretion.

TRH synthesized in hypophysiotropic neurons of the hypothalamic paraventricular nucleus (PVN) stimulates the release of TSH and prolactin from the anterior pituitary gland. Recent data from our laboratories have demonstrated that TRH and cocaine- and amphetamine-regulated transcript (CART) are co-contained only in hypophysiotropic neurons in the PVN. To determine whether CART and TRH interact in the regulation of anterior pituitary function, we have studied the effects of CART on TRH-induced release of TSH and prolactin in anterior pituitary cell cultures, and the effects of hypo- and hyperthyroidism on CART mRNA in the PVN. Dispersed anterior lobe cells from male rats were treated with CART (10(-6), 10(-8), 10(-10), and 10(-12) m) or TRH (10(-7) m) alone and TRH (10(-7) m) combined with various concentrations of CART for 4 h at 37 C. The medium was assayed for prolactin and TSH by RIA. TRH resulted in a marked increase of both prolactin and TSH release, whereas CART had no effect on prolactin or TSH secretion. When the two peptides were used in combination, CART dose-dependently inhibited TRH-induced prolactin release but had no significant effect on TRH-induced TSH release. By semiquantitative analysis of in situ hybridization autoradiographs, CART mRNA was significantly elevated in hypothyroid animals, whereas a reduction in CART mRNA was observed in hyperthyroid animals compared with euthyroid controls. These data raise the possibility that CART expressed in hypophysiotropic TRH neurons has an important role in the modulation of TRH-induced prolactin secretion. Increased secretion of CART may be responsible for the reduced TRH-induced prolactin response during hypothyroidism.

Observer variability of tibial plateau slope measurement in 40 dogs with cranial cruciate ligament-deficient stifle joints.

OBJECTIVE: To determine (1) the inter- and intraobserver variability in measurement of tibial plateau angle (TPA), (2) whether this inter- and intraobserver variability is related to the characteristics of the dog (age, size, and amount of degenerative joint disease [DJD]) and the experience level of the observer, and (3) the extent of any relationship between interobserver variability of TPA and the variability of the observers' selection of the specific cranial and caudal points along the tibial plateau. STUDY DESIGN: Examination of tibial radiographs of 40 dogs clinically affected with a cranial cruciate ligament (CrCL)-deficient stifle joint. METHODS: Eleven different observers, divided into 3 groups based on their level of experience with the tibial plateau leveling osteotomy (TPLO) technique, measured the TPA on all 40 radiographs on 5 different occasions. The degree of DJD present in the stifle joint was independently graded as an overall measure and then again as it specifically related to the cranial and caudal points along the tibial plateau. The total observed variabilities of the TPA were assessed with reference to interobserver differences, intraobserver differences, and among the groups of observers with respect to the different dog characteristics. Finally, the specific points selected on the radiographs were reexamined to determine whether any variability was present in cranial and caudal point selection. RESULTS: The interobserver standard deviation of the TPA measurements for each dog was 0.8 degrees, and the intraobserver standard deviation was 1.5 degrees. The TPA measurements obtained by the 11 observers differed significantly from each other (P <.001); however, there was no significant difference of TPA among the different groups of observers (P =.67). There was no significant correlation observed between either the inter- or intraobserver variability and the dog characteristics. Specific point data and their relationship to the various variables of dog characteristics and inter- and intraobserver TPA variability revealed significant correlations only to the amount of DJD present at the caudal point (P =.001). CONCLUSIONS: Interobserver variation, but no significant group variation, was present. Overall DJD did not appear to be related to the variability in TPA angle measurement. Most of the interobserver variability was attributable to variability in horizontal point selection at both the cranial and caudal points and vertical point selection at the caudal point. It appears that degenerative changes that specifically obscure the points on the tibial plateau, especially at the caudal point, are responsible for most of the interobserver variation. CLINICAL RELEVANCE: The desired postoperative TPA of 5 degrees is dependent on a precise initial measure of TPA preoperatively. This study indicates that there is statistically significant interobserver variability with measurement of TPA, which, therefore, can result in a similar amount of variability with the final tibial plateau slope obtained postoperatively.

M-mode echocardiographic ratio indices in normal dogs, cats, and horses: a novel quantitative method.

A novel method for quantitative echocardiographic interpretations is introduced based on the calculation of ratio indices in which each raw M-mode measurement is divided by the aortic root dimension (Ao). "Aorta-based" indices were calculated with the animal's measured aortic root dimension (Ao(m)) as the length standard. Conversely, "weight-based" indices employed an idealized estimate of aortic dimension (Ao(w)) with a weighted least squares linear regression against the cube root of body weight (Ao(w) = kW(1/3)). Use of these indices circumvented undesirable statistical characteristics inherent in linear regression of echocardiographic dimensions against body weight and, to a lesser extent, body surface area. Compared with the regressions, ratio indices resulted in substantial refinement of the predictive range for each M-mode measurement in dogs, particularly with decreasing body size. Weight-based indices outperformed aorta-based indices in this regard. To refine the predictive range, neither type of index was clearly advantageous in cats compared with the simple average method typically employed for that species. Several of the raw M-mode measurements, however, were correlated with body weight in cats and horses, indicating the need for an appropriate correction for body size in these species. The ratio index method was suitable for this purpose. Summary statistics derived from normal dogs (n = 53), cats (n = 32), and horses (n = 17) are presented for each index, including novel clinical indices calculated from area ratios. The latter were designed to represent body size-adjusted lett ventricular stroke area (ie, volume overload) and myocardial wall area (ie, hypertrophy).

Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma.

Toxicosis associated with doxorubicin and cisplatin administration starting either 2 or 10 days after limb amputation for osteosarcoma was examined retrospectively in dogs. The purpose was to determine whether dosage and timing of chemotherapy affected rates of toxicosis after administration of the 1st treatment. Records of 100 dogs with appendicular osteosarcoma without evidence of metastases or concurrent disease were examined. Dogs received chemotherapy with doxorubicin and cisplatin every 3 weeks for 3 treatments starting 2 days (n = 51) or 10 days (n = 49) after amputation. The dosage of cisplatin was 60 mg/m2 and was given with 6-hour saline diuresis and butorphanol. Doxorubicin was given at 12.5-25 mg/ml during fluid administration. Hematologic data were collected before and weekly after treatment. Client interviews were conducted to assess gastrointestinal toxicosis during the interval between treatments. The reported toxicoses were graded on a scale of 0 to 4. Dogs receiving 25 mg/m2 of doxorubicin experienced greater rates of grade 4 toxicity (67%; n = 6) than dogs in groups receiving 12.5-20 mg/m2 of doxorubicin (< or = 25%; n = 94, P = .03). Dogs in the Day 2 group experienced greater rates (35%) of grade 4 toxicity than dogs in the Day 10 group (12%, P = .007). We concluded that chemotherapy administered 2 days after surgery produced an unacceptable level of toxicoses. except at greatly reduced dosages, and that even with a delay of treatment, 25 mg/m2 of doxorubicin, when given in combination with cisplatin at 60 mg/m2, was too toxic for routine use.

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function.

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.