Glucocorticoid receptor density and binding affinity in healthy horses and horses with systemic inflammatory response syndrome.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in horses with systemic inflammatory response syndrome (SIRS). Peripheral resistance to glucocorticoids has not been investigated in horses. OBJECTIVE: To determine if glucocorticoid receptor (GR) function in horses can be measured using flow cytometry, and to use this information to evaluate HPA axis dynamics. ANIMALS: Eleven healthy adult horses in parts 1 and 2. Ten horses with SIRS and 10 age and sex matched controls in part 3. METHODS: Flow cytometry was used to evaluate GR density and binding affinity (BA) in 3 healthy horses in part 1. In part 2, exogenous ACTH was administered to eight healthy horses. Their cortisol response and GR properties were measured. In part 3, CBC, serum biochemistry, cortisol and ACTH, and GR properties were compared between controls without SIRS (n = 10) and horses with SIRS (n = 10), and between survivors and nonsurvivors (n = 4 and n = 6 respectively). RESULTS: Flow cytometry can be used to measure GR properties in equine PBMCs. No correlation was observed between plasma cortisol concentration and GR density or BA in healthy horses (r = -0.145, P = .428 and r = 0.046, P = .802 respectively). Nonsurvivors with SIRS had significantly decreased GR BA (P = .008). Horses with triglyceride concentration > 28.5 mg/dL had increased odds of nonsurvival (OR=117; 95% CI, 1.94-7,060). GR BA <35.79% was associated with nonsurvival (OR = 30.33; 95% CI, 0.96-960.5). CONCLUSIONS AND CLINICAL IMPORTANCE: Tissue resistance to glucocorticoids contributes to HPA axis dysfunction in adult horses with SIRS. These horses might benefit from treatment with exogenous glucocorticoids.

Prognosis for racing with conservative management of cervical vertebral malformation in thoroughbreds: 103 cases (2002-2010).

BACKGROUND: Cervical vertebral malformation (CVM) is seen in young, rapidly growing horses, and is commonly associated with a poor prognosis for racing. HYPOTHESIS/OBJECTIVE: To examine the records of a population of Thoroughbreds with a presumptive diagnosis of CVM and to determine which radiographic findings and neurologic exam findings have an effect on these horses achieving athletic function when managed conservatively. ANIMALS: One hundred and three thoroughbreds presumptively diagnosed with CVM and treated conservatively between 2002 and 2010. METHODS: Racing records were reviewed in this retrospective study to determine which horses raced after treatment. Horses were separated into groups based on whether or not they raced. Medical records were reviewed, and results of neurologic examination, radiographic and laboratory findings, treatments, and outcome were assessed and compared between groups. RESULTS: Sixteen horses were excluded because of insufficient information. Of the remaining horses, thirty-three were euthanized after diagnosis, while the remaining seventy were discharged for treatment. Twenty-one of 70 horses treated medically (30%) went on to race. Horses that went on to race had a significantly lower neurologic grade (P = .0002), with a median of 1.0 in the thoracic limbs and 2.0 in the pelvic limbs. Euthanized horses and nonstarters were more likely to have kyphosis (P = .041) or cranial stenosis (P = .041) on standing lateral cervical radiographs. CONCLUSIONS AND CLINICAL IMPORTANCE: Some horses can race after the diagnosis of CVM. Neurologic examination and radiographic findings can be helpful in predicting racing prognosis.

Effect of an integrated support programme on the concerns and wellbeing of women with breast cancer: a national service evaluation.

PURPOSE: To carry out a national service evaluation of the integrated cancer support programme offered by The Haven using the Measure Yourself Concerns and Wellbeing (MYCaW) outcome questionnaire. METHODS: Breast cancer survivors who visited one of three Haven centres in the UK completed the MYCaW questionnaire before and after 6 one-hour complementary therapy sessions. RESULTS: Statistically significant decreases in mean baseline scores (indicating improvement) for concerns and wellbeing were observed after treatment: concern 1 (5.09 ± 1.04 vs 3.17 ± 1.60, p < 0.0001, n = 402), concern 2 (4.69 ± 1.08 vs 3.08 ± 1.56, p < 0.0001, n = 372), and wellbeing (3.30 ± 1.41 vs 2.63 ± 1.28, p < 0.0001, n = 402). The therapies most commonly used were acupuncture, nutrition, massage and aromatherapy, shiatsu, counselling and reflexology. After therapy, 91% of reported scores (n = 328) rated the concern as being a little better, much better or gone. CONCLUSIONS: These findings suggest that women with breast cancer find the Haven integrated support programme valuable for addressing their main concerns and improving their feeling of wellbeing.

Lipoprotein(a) level does not predict restenosis after percutaneous transluminal coronary angioplasty.

The serum lipoprotein(a) [Lp(a)] level is a known risk factor for arteriosclerotic coronary artery disease. However, its association with restenosis after percutaneous transluminal coronary angioplasty (PTCA) is controversial. We hypothesized that the Lp(a) level is a significant risk factor for restenosis after angioplasty through a pathophysiological mechanism leading to excess thrombin generation or inhibition of fibrinolysis. We designed a prospective study of the relation of Lp(a) to outcome after PTCA, in which we measured selected laboratory variables at entry and collected clinical, procedural, lesion-related, and outcome data pertaining to restenosis. Restenosis was defined as >50% stenosis of the target lesion by angiography or as ischemia in the target vessel distribution by radionuclide-perfusion scan. Before the patients underwent PTCA, blood was obtained by venipuncture for measurement of Lp(a), total cholesterol, thrombin-antithrombin (TAT) complex, alpha2-antiplasmin-plasmin (APP) complex, and plasminogen activator inhibitor-1 (PAI-1). Evaluable outcome data were obtained on 162 subjects, who form the basis of this report. Restenosis occurred in 61 subjects (38%). The Lp(a) level was not correlated significantly with TAT, APP, PAI-1, or the TAT-APP ratio. Levels of TAT, APP, and PAI-1 were not statistically different in the patients with versus those without restenosis. The median ratio of TAT to APP was 2-fold higher in the restenosis group, and this difference approached statistical significance (P=0.07). Univariate analysis was performed for the association of clinical, lesion-related, and procedural risk factors with restenosis. Lp(a) levels did not differ significantly in the restenosis versus no-restenosis group, whether assessed categorically (>25 mg/dL versus <25 mg/dL) or as a continuous variable by Mann-Whitney U test. The number of lesions dilated and the lack of family history of premature heart disease were significantly associated with restenosis (P=0.002 and P=0.008, respectively). A history of diabetes mellitus was of borderline significance (P=0.055). By multiple logistic regression analysis, the number of lesions dilated was the only variable significantly associated with restenosis (P=0.03). We conclude that the number of lesions dilated during PTCA is a significant risk factor for restenosis, whereas the serum Lp(a) level was not a significant risk factor for restenosis in our patient population. The TAT to APP ratio merits further study as a possible risk factor for restenosis.

Imaging of primary multifocal osseous lymphoma.

OBJECTIVE: To review our experience with primary multifocal osseous lymphoma (PMOL), to characterize its imaging features, before and after treatment, and to correlate these features with clinical outcome. DESIGN: Hospital charts and imaging studies in eight patients with PMOL were reviewed. These included bone radiographs, bone scans, CT and MRI. Number, distribution and appearance of lesions before treatment were evaluated; and post-treatment changes were assessed for evidence of healing or progression, correlated with clinical outcome. RESULTS: A total of 63 lesions were identified by pre-treatment bone scan, 36 by MRI (including 10 not visible on bone scan) and 16 by radiographs. Twenty-one percent of lesions occurred about the knee, and 63% of patients had concomitant skull, distal femoral and proximal tibial lesions. The radiographic appearance ranged from lytic to sclerotic. Lesions were isointense to hematopoietic marrow on T2-weighted MR sequences. Only plain radiographic evidence of healing or progression correlated with clinical outcome. CONCLUSION: Distribution of PMOL was best assessed by bone scan. However, MRI revealed larger areas of marrow involvement and detected lesions in the pelvis not seen on bone scan. Marrow involvement around the knee was common, and the combination of skull, distal femoral and proximal tibial lesions may suggest the diagnosis. Radiographs underestimate the extent of disease but were the best modality for assessment of treatment response.

Trends in contact lens-associated corneal ulcers.

Charts of 320 patients with corneal ulcers seen on the Cornea Service of Wills Eye Hospital from July 1, 1992, to June 30, 1995, were reviewed retrospectively. Of these cases, 96 (30%) were associated with contact lens use. Ulcers in contact lens users accounted for 36% of cases in the last 6 months of 1992 and all of 1993, 20% of cases in 1994, and 29% in the first 6 months of 1995. The contact lenses most commonly associated with ulcers were disposable extended-wear lenses. They were used in 33% of contact lens-associated ulcers in 1992, 27% in 1993, 39% in 1994, and 44% in 1995. Pseudomonas was the predominant organism prior to 1993 (1-4). From 1993 to 1995, however, the number of Pseudomonas ulcers steadily decreased. Two or three Acanthamoeba infections continue to be treated each year. There has been a significant decrease in the number of contact lens-related ulcers treated at our institution compared with previous years (p < 0.01) (3, 4).

Postprandial elevation of activated factor VII in young adults.

The Northwick Park Heart Study found that factor VII (FVII) activity was a risk factor for ischemic heart disease, and other studies based on indirect assays of activated factor VII (FVIIa) found an elevation of FVIIa postprandially. We hypothesized that postprandial elevation of FVIIa would produce intermittent activation of factor X to Xa and, subsequently, prothrombin to thrombin. We chose to study postprandial activation of coagulation with a new assay specific for FVIIa that uses soluble tissue factor and with a prothrombin fragment 1 + 2 (F1 + 2) assay to detect the activation of prothrombin by factor Xa. We fed a high-fat breakfast (30 g/m2) to 30 healthy volunteer subjects (30.8 +/- 9.8 years; range, 20 to 49 years) on no medication. Fasting blood samples were collected for FVIIa, FVII antigen (FVIIag). and F1 + 2 as well as triglycerides and total and HDL cholesterol. A significant difference was found between fasting (2.82 +/- 1.49 ng/mL. mean +/- SD) and 6-hour postprandial (3.45 +/- 2.08 ng/mL) FVIIa levels (P < .004); FVIIag did not change significantly (mean, 0.89 U/mL fasting and 0.90 U/mL at 6 hours). In contrast, F1 + 2 levels were slightly lower 6 hours postprandially than fasting (median, 0.39 versus 0.44 nmol/L, P < .02). Four-hour postprandial triglyceride levels correlated significantly (p = 0.51, P < .02) with 6-hour postprandial FVIIag but not with 6-hour postprandial FVIIa. Postprandial F1 + 2 levels (at 6 hours) correlated significantly (p = 0.39, P < .04) with fasting FVIIag levels but not with 6-hour postprandial FVIIa levels. Thus, the basal FVIIag level, in the fasting state, may be involved in control of the generation of F1 + 2. We found a postprandial increase in FVIIa levels after a dietary fat load but did not find a concomitant postprandial burst of activation of factor X and prothrombin as measured by F1 + 2. Further studies are to test whether postprandial FVIIa generation leads to enhanced activation of coagulation.

Correlation of vitamin K-dependent clotting factors with cholesterol and triglycerides in healthy young adults.

The plasma level of factor VII activity was a risk factor for the development of ischemic heart disease (IHD) in a prospective epidemiological study of hemostatic factors. We have previously reported significant correlations between factor VII clotting activity or antigen and lipid fractions in a group of 132 young men (< 30 years old) at low risk for IHD and concluded that control of the plasma factor VII level may be linked to lipid metabolism in normal male physiology. Because factor VII is one of four vitamin K-dependent procoagulant proteins, we hypothesized that plasma levels of all these proteins would be similarly controlled in normal physiology. In an extension of this study, we have measured two additional vitamin K-dependent clotting factors (prothrombin [factor II] and factor X activity), as well as factor VII activity and antigen and fasting serum lipid fractions in healthy young men and women (< 30 years old) at low risk for IHD. In the women, we found significant positive correlations of factor VII antigen with total or HDL cholesterol and of prothrombin or factor X with total or LDL cholesterol. In the men, factor VII activity or antigen correlated with total cholesterol, triglycerides, HDL cholesterol, or LDL cholesterol; prothrombin or factor X correlated with total cholesterol, triglycerides, or LDL cholesterol. In contrast, we found no significant correlations of fibrinogen with any of the lipid fractions in our groups of men or women. Our data support the hypothesis that control of the levels of the vitamin K-dependent procoagulant proteins is linked to lipid metabolism in the normal physiology of both men and women.

Strategies for using university health services for cholesterol screening.

Seven hundred seventy students, parents, and employees participated in free cholesterol screenings during key promotional events at Central Michigan University between 1989 and 1992. Participants were self-selected volunteers who wanted to know their cholesterol levels. More than one third of the participants (32.4% of the students, 38.0% of the parents, and 54.3% of the employees) were found to have borderline or high cholesterol readings that put them at risk of coronary artery disease (CAD) because of hypercholesterolemia. The screening may have attracted subjects with a family history of CAD or other risk factors, and these individuals need follow-up lipid profiles and cholesterol education. The authors provide a description of the innovative approaches of their program and offer suggestions for promotional cholesterol screening programs.

Marital status of daughters and patterns of parent care.

Patterns of help to disabled elderly parents from family and paid sources are examined as they vary among five groups of parent-caring daughters: married (n = 234), remarried (n = 56), separated/divorced (n = 91), widowed (n = 52), and never married (n = 59). Parents of all groups received similar total amounts of care from all sources combined, with daughters providing at least half of the care themselves. Never-married daughters, followed by the widowed, provided larger proportions of the total hours of care (77% and 62%) than the other three groups (p < .001). Married daughters had the most informal helpers (p < .001), and never marrieds more often were their parents' sole informal helpers (p < .01). Separated/divorced women who shared households used the highest proportions of paid care.

Vitamin K-dependent clotting factors are elevated in young adults who have close relatives with ischemic heart disease.

An increase in factor VII was found to be a risk factor for ischemic heart disease. The present study was designed to test the hypothesis that this increase in factor VII is part of a general increase in vitamin K-dependent clotting factors. Initially, a prospective analysis of factor VII antigen and prothrombin activity was performed in two groups of young subjects without symptoms who differed in their risk of ischemic heart disease based on a history (or lack thereof) of premature heart disease in a first-degree relative. A statistically significant increase in prothrombin activity and factor VII antigen was found in the high-risk group of subjects when compared with the low-risk group. In a second series of subjects, factor IX and X activity assays were also performed, and all four of the vitamin K-dependent clotting factors were found to be significantly higher in high-risk subjects when compared with low-risk subjects. A second goal of the study was to explore whether correlations between factor VII and cholesterol and triglycerides might be due to binding of factor VII with apolipoprotein B. Although a significant correlation of factor VII antigen with apolipoprotein B (rho = 0.523, p < 0.025) was found in our high-risk group of subjects, the correlation between factor VII and triglycerides (rho = 0.641, p < 0.005) was even stronger statistically, suggesting a probable interaction of factor VII with very-low-density lipoproteins in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma fibrinogen level is not elevated in young adults from families with premature ischemic heart disease.

Several epidemiological studies have found that the plasma fibrinogen level is a risk factor for ischemic heart disease (IHD), similar in importance to the serum cholesterol level. A family history of IHD is also a significant risk factor for IHD, statistically independent of the serum cholesterol level. Whether the familial risk for IHD is related to genetic control of the fibrinogen level is unknown. Estimates of the genetic contribution to the variance in plasma fibrinogen levels vary markedly. We previously found elevated levels of cholesterol and factor VII in young subjects with a familial history of premature IHD. In the present study we chose to measure fibrinogen, factor VII antigen, and total cholesterol levels in 43 asymptomatic first-degree relatives (< 50 years old) of patients with premature IHD and in 43 age- and sex-matched asymptomatic young adults at low risk of IHD. No subjects in either group were smokers. The mean plasma fibrinogen level of the high-risk group (259 mg/dL) did not differ significantly from that of the low-risk group (250 mg/dL; p > 0.4). In contrast, the high-risk group had significantly higher mean factor VII antigen (p < 0.001) and mean serum cholesterol (p < 0.0001) than the low-risk group. These data argue against the hypothesis that genetic determination of the plasma fibrinogen level is a common pathophysiological mechanism responsible for familial risk of IHD.

A nutrition survey of and recommendations for individuals with Prader-Willi syndrome who live in group homes.

The purpose of this study was to describe anthropometric data and identify diet-related problems of individuals with Prader-Willi syndrome (PWS) who reside in group homes. A group home is a licensed foster care facility that provides 24-hour care for the developmentally disabled. Questionnaires were sent to dietitians (or the person responsible for nutrition care) of 25 group homes; responses from 18 homes were analyzed. The mean age of residents with PWS was 25 +/- 8.4 years and the mean height was 152.4 +/- 9.7 cm. The mean weight for 19- to 22-year-old men was 75.5 +/- 26.8 kg and that for women of the same age was 74.5 +/- 20 kg. The residents consumed a mean of 1,000 to 1,500 kcal/day. Most of the group homes (n = 16) locked their kitchens at night, and in 12 of the homes stealing and hoarding of food occurred. Pica behavior (eating of nonfoods) was reported in 7 homes. One third of all residents had success in weight loss and were on a maintenance diet, but a major problem was determination of a desirable weight goal. Our key recommendations for dietitians are weigh residents weekly; use the body mass index with prescribed zones for determination of weight goals; monitor change in circumference measurements; follow the guidelines of 7 to 8 kcal/cm of height for weight loss and 10 to 14 kcal/cm of height for weight maintenance; administer 1,000 kcal/day or more and encourage daily aerobic exercise; respect food preferences while adhering to dietary prescriptions; adhere to strict food control procedures; and use nutrition education methods and an interdisciplinary approach for behavior modification.

Correlation of factor VII activity and antigen with cholesterol and triglycerides in healthy young adults.

Prospective epidemiological studies found that the plasma level of factor VII activity was a risk factor for ischemic heart disease (IHD). Our laboratory previously demonstrated that young adults (mean age, 35 years) at high risk of IHD had significantly higher plasma factor VII activity and antigen levels than did comparable young adults at low risk. To study the relation of factor VII with lipid metabolism in even younger adults (less than 30 years), using standard techniques we measured plasma factor VII activity and antigen, plasma fibrinogen, and fasting serum lipid fractions in healthy male and female subjects who were at low risk of IHD and who were not on medication. Factor VII antigen correlated significantly with total serum cholesterol, fasting serum triglycerides, and high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol (p less than 0.01), and factor VII activity correlated with total and HDL cholesterol (p less than 0.05) in the men (n = 132); however, fibrinogen level did not correlate significantly with any lipid level in this group. We found no significant correlation of factor VII activity or antigen with any lipid levels in the women (n = 65). Our data support the hypothesis that control of plasma factor VII level is linked to lipid metabolism in normal physiology in men. Thus, factor VII level may reflect the mechanism by which male gender imparts added risk for IHD, independent of other established risk factors. This study also supports the use of the factor VII antigen assay, a highly reproducible method, in studies of the relation of factor VII to the risk of IHD.

An eating plan and update on recommended dietary practices for the endurance athlete.

This article presents a six-group exchange food plan for the endurance athlete. The plan allows approximately 1,850, 3,460, and 3,760 kcal for a weight reduction diet, general training diet, and carbohydrate-loading intake plan, respectively. Because complex carbohydrate is the primary source of fuel, the training diet and the carbohydrate-loading diet contain 500 g and 600 g carbohydrate, respectively, whereas in the weight reduction plan more than 60% of total energy is carbohydrate. Overall nutrient adequacy of the exchanges and fluid needs for the athlete are discussed. Recommendations and protocol for current dietary practices are given. Dietitians are encouraged to assess the caloric needs of their clients and to individualize the suggested plans in accordance with the needs of each athlete.