Effect of oral calcium bolus supplementation on early-lactation health and milk yield in commercial dairy herds.

The objective of this study was to evaluate the effect of supplementation with oral Ca boluses after calving on early-lactation health and milk yield. Cows in their second lactation or greater (n=927) from 2 large dairies in Wisconsin were enrolled during the summer of 2010. Both herds were fed supplemental anions during the prefresh period and less than 1% of fresh cows were treated for clinical milk fever. Cows were scored before calving for lameness and body condition, and then randomly assigned to either a control group or an oral Ca bolus-supplemented group. Control cows received no oral Ca boluses around calving. Cows in the oral Ca bolus group received 2 oral Ca boluses (Bovikalc, Boehringer Ingelheim, St. Joseph, MO), one bolus 0 to 2h after calving and the second 8 to 35 h after calving. The oral Ca bolus administration schedule allowed fresh cows to be restrained in headlocks only once daily. Whole-blood samples were collected immediately before the second oral Ca bolus was given and were analyzed for ionized Ca (Ca(2+)) concentration. Early-lactation health events were recorded and summed for each cow. Only 6 cases (0.6% of calvings) of clinical milk fever occurred during the trial, and only 14% of cows tested were hypocalcemic (Ca(2+) less than 1.0 mmol/L) at 8 to 35 h after calving. Mean Ca(2+) concentrations were not different between the control and oral Ca bolus-supplemented groups. Blood samples from the cows given oral Ca boluses were collected an average of 20.6 h after administration of the first bolus. Subpopulations of cows with significant responses to oral Ca bolus supplementation were identified based on significant interactions between oral Ca bolus supplementation and covariates in mixed multiple regression models. Lame cows supplemented with oral Ca boluses averaged 0.34 fewer health events in the first 30 d in milk compared with lame cows that were not supplemented with oral Ca boluses. Cows with a higher previous lactation mature-equivalent milk production (greater than 105% of herd rank) and supplemented with oral Ca boluses produced 2.9 kg more milk at their first test after calving compared with cows with higher previous lactation milk yields that were not supplemented. Results of this study indicate that lame cows and higher producing cows responded favorably to supplementation with oral Ca boluses. Supplementing targeted subpopulations of cows with oral Ca boluses was beneficial even for dairies with a very low incidence of hypocalcemia.

Sialochemistry and cortisol levels in patients with Sjogren's syndrome.

OBJECTIVES: (i) To determine whether salivary cortisol and electrolyte levels differ between patients with Sjogren's syndrome (SjS) and healthy individuals. (ii) To assess correlations between whole-saliva cortisol and some clinical manifestations in patients with SjS. METHODS: A total of 24 healthy women (mean age 49.3±9.8) served as controls (C) vis-à-vis 17 patients with SjS (mean age 55.5±15.7). Salivary cortisol concentration was determined, and sialochemistry analysis was performed. RESULTS: Significantly lower saliva flow rates and higher salivary chloride (Cl(-) ), potassium (K(+) ), and Ca(2+) levels were found in the SjS group. No significant differences or correlations were found in other parameters, including sodium (Na(+) ), magnesium (Mg(2+) ), phosphate ((-) ), urea (U), and salivary cortisol levels. CONCLUSION: Increased whole-salivary output of Cl(-) and K(+) in SjS may reflect release from apoptotic rests of acinar cells after secondary necrosis. Normal levels of salivary Na(+) , Mg(2+) , and (-) argue against concentration effect, deranged tubular function or cortisol (mineralocorticosteroid) effect as the cause for these findings. Increased salivary Ca(2+) levels probably reflect leakage of plasma Ca(2+) through the injured oral mucosa in SjS. In spite of disease-associated stress, salivary cortisol, a stress biomarker, was not increased, suggesting insufficient hypothalamus-pituitary-adrenal (HPA) axis response and/or local consumption of cortisol by lymphocyte infiltrates.

Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD.

Surfactant protein (SP)-D is a lung-derived protein that has been proposed as a biomarker for inflammatory lung disease. Serum SP-D was evaluated as a biomarker for components of chronic obstructive pulmonary disease (COPD) in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort and its response assessed to the administration of the anti-inflammatory agent prednisolone. The median level of serum SP-D was significantly elevated in 1,888 individuals with COPD compared to 296 current and former smokers without airflow obstruction (121.1 and 114.3 ng x mL(-1), respectively; p = 0.021) and 201 nonsmokers (82.2 ng x ml(-1); p<0.001). There was no correlation with the severity of COPD. Individuals with COPD who had a serum SP-D concentration that was greater than the 95th percentile of nonsmokers (175.4 ng x mL(-1)) showed an increased risk of exacerbations over the following 12 months (adjusted OR 1.30; 95% CI 1.03-1.63). Treatment with 20 mg x day(-1) prednisolone for 4 weeks resulted in a fall in serum SP-D levels (126.0 to 82.1 ng x mL(-1); p<0.001) but no significant change in post-bronchodilator forced expiratory volume in 1 s. Serum SP-D concentration is raised in smokers and may be useful in identifying individuals who are at increased risk of exacerbations of COPD. It may represent an intermediate measure for the development of novel anti-inflammatory agents.

Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort.

BACKGROUND: Circulating levels of Clara cell secretory protein-16 (CC-16) have been linked to Clara cell toxicity. It has therefore been suggested that this protein may be a useful marker of chronic obstructive pulmonary disease (COPD). METHODS: Serum CC-16 levels were measured in 2083 individuals aged 40-75 years with COPD and a smoking history of >or=10 pack-years, 332 controls with a smoking history of >or=10 pack-years and normal lung function and 237 non-smoking controls. RESULTS: Serum CC-16 had a coefficient of repeatability of 2.90 over 3 months in a pilot study of 267 individuals. The median serum CC-16 level was significantly reduced in a replication group of 1888 current and former smokers with COPD compared with 296 current and former smokers without airflow obstruction (4.9 and 5.6 ng/ml, respectively; p<0.001) and 201 non-smokers (6.4 ng/ml; p<0.001). Serum levels of CC-16 were lower in current than in former smokers with GOLD stage II and III COPD but were not different in individuals with stage IV disease. Former, but not current smokers, with COPD had lower serum CC-16 levels with increasing severity of COPD (GOLD II vs GOLD IV COPD: 5.5 and 5.0 ng/ml, p = 0.006; r = 0.11 with forced expiratory volume in 1 s, p<0.001) and had significantly higher levels if they also had reversible airflow obstruction (p = 0.034). Serum CC-16 was affected by gender and age (r = 0.35; p<0.001) in subjects with COPD but not by body mass index or the presence of either chronic bronchitis or emphysema. CONCLUSIONS: Serum CC-16 levels are reduced in individuals with COPD and there is a weak correlation with disease severity in former smokers.

A one-step, competitive electrochemiluminescence-based immunoassay method for the quantification of a fully human anti-TNFalpha antibody in human serum.

A quantitative, one-step, competitive electrochemiluminescence (ECL)-based immunoassay for the determination of a fully human, anti-TNFalpha monoclonal antibody in human serum has been developed. A biotinylated, mouse anti-variable region-specific antibody and a ruthenium-labeled anti-TNFalpha antibody were the only specific reagents needed to develop the assay. A single incubation step of 2 h followed by ECL detection was used. The assay was capable of measuring the analyte in neat serum over approximately a 1600-fold range with higher concentrations measured following a single dilution. Assay accuracy, precision, and reproducibility were suitable to support pharmacokinetic studies of the analyte. This competitive assay format offers an alternative approach to the development of immunoassays for the measurement of macromolecules in complex matrices to support preclinical and clinical studies.

Gynecologic cancer patients' psychosocial needs and their views on the physician's role in meeting those needs.

The aim of this study was to identify the psychosocial needs of patients after treatment for gynecological malignancies and their views concerning the role physicians should take in meeting those needs. Self-administered questionnaires were answered by 95 patients at least 6 months after completion of therapy. Topic areas included emotional needs, spiritual concerns, patient-family communication, patient participation in decision making, and advance directives. In addition, all participants completed the Functional Assessment of Cancer Therapy (FACT-G, version 4) quality of life questionnaire. Fifty-seven percent of respondents stated that they had needed help dealing with emotional problems, and 73% wanted the physician to ask whether help is needed. The most common emotional concerns were feeling nervous (40% of subjects), being worried (34%), fear (25%), needing someone to talk to (24%), sadness (21%), and loss of control (17%). Fifty-nine percent stated that physicians should ask whether help is needed in discussing spiritual matters. Sixty-one percent stated that physicians should ask patients whether they want help starting conversations with their families about difficult-to-raise topics such as the possibility of dying. Forty-six of 86 respondents (53%) stated that discussions about advance directives such as living wills should take place soon after the cancer diagnosis has been established. Most patients surveyed want physicians to take an active role in dealing with psychosocial needs.

Alcohol misuse among college athletes: self-medication for psychiatric symptoms?

A collegiate athlete population was surveyed for alcohol abuse as well as self-reported depression, anxiety, and other psychiatric symptoms. This study revealed that in a group of 262 athletes there were 21 percent who reported high alcohol use and problems associated with its use. Significant correlations were found between reported alcohol abuse and self-reported symptoms of depression and general psychiatric symptoms. Subjects with positive depression and psychiatric symptom ratings in the "severe" range had a significantly higher rate of alcohol abuse than subjects who had low depression and low or mild symptom ratings. Conversely, subjects reporting higher rates of alcohol misuse had more psychiatric symptoms. These findings suggest a possible causal link between psychopathology and serious alcohol abuse among college athletes. They also point to the need for routine depression and anxiety screening in college students who are typically beginning a significant exposure to alcohol.

Breast cancer risk assessment in patients seen in a gynecologic oncology clinic.

The objective of this study was to determine if breast cancer risk assessment following the Gail model should be incorporated into a gynecologic oncology clinic. The Gail model was used to assess the risk of breast cancer in 329 patients with preinvasive lower genital tract disease (Pre, n = 86), invasive vulvar and cervical (Cx, n = 102), uterine (Ut, n = 87), and ovarian cancer (Ov, n = 54) seen in an inner city gynecologic oncology office. T-test, chi square test, and Pearson and Spearman correlation coefficients were used for statistical evaluation. A P-value of less than 0.05 was regarded significant. An estimated 5-year risk of breast cancer of 1.67 or more was noted in 9% of the Pre patients, 5% of Cx patients, 21% of the Ut patients, and 9% of the Ov patients. The difference between Cx and Ut patients was significant. The average 5-year risk was calculated at 0.77 for Pre patients, 0.77 for Cx patients, 1.18 for Ut patients, and 1.11 for Ov patients. These differences were significant, but mirror the age distribution. The average age was 43.6 for Pre patients, 52.2 years for Cx, 61.5 years for Ut, and 58.5 years for Ov patients; these differences were significant. When calculations were corrected for the mean age (53 years), there were no significant differences between groups regarding the average risk: Pre: 1.04, Cx: 0.81, Ut: 0.96, Ov: 0.97. Only eight patients (2.4%), six of them in the Pre and Cx group, would be expected to derive significant benefit from tamoxifen therapy. We conclude that elevated 5-year breast cancer risk to 1.67% or higher is noted in about 11% of patients seen in a gynecologic oncology office, mainly related to age and family history. Risk assessment and regular screening should be part of any follow-up exam.

Secondary ovarian neoplasms in children: imaging features with histopathologic correlation.

BACKGROUND: Although the pathologic features and imaging appearance of childhood primary ovarian neoplasms have been well described, little information is available about the malignancies that may secondarily involve the ovary. OBJECTIVE: To determine the relationship between the imaging features and the histopathology of secondary ovarian neoplasms in children treated at our institution. MATERIALS AND METHODS: We searched our institutional database for codes indicating metastatic ovarian disease. Of the 35 patients with such codes, 18 had pathologically proven secondary ovarian disease. From their medical records we recorded demographic data, presenting symptoms, and evidence of endocrine dysfunction. We reviewed the pre-oophorectomy imaging and the subsequent pathologic specimens. RESULTS: One-third of the patients had bilateral pelvic masses; another third had large masses indistinguishable from the ovaries. Twelve (67%) had either ascites, peritoneal implants, matted bowel, adenopathy, pleural effusions, or some combination of these. Five (28%) had other metastatic disease. Primary tumors included colon adenocarcinoma (9), Burkitt's lymphoma (3), alveolar rhabdomyosarcoma (3), Wilms' tumor (1), neuroblastoma (1), and retinoblastoma (1). CONCLUSION: Although rare, secondary ovarian tumors should be considered in the differential diagnosis of children with ovarian masses. Bilateral ovarian masses or large masses indistinguishable from the ovaries, particularly in the presence of other metastatic foci, may help distinguish primary from secondary ovarian malignancies.

Parameters of differentiation and proliferation in adult granulosa cell tumors of the ovary.

We evaluated parameters of cell differentiation and proliferation to improve prognostication of ovarian adult granulosa cell tumors. Recurrent tumors (n = 10, REC group) and nonrecurrent tumors (n = 30, NED group) were compared in terms of cellular atypia, nuclear area, p53 overexpression, ploidy, DNA index, mitosis count, S-phase fraction, and nucleolar organizer region number and area per cell. Cellular atypia was significantly more frequent in REC than NED tumors (50% versus 13%; P = .03). Mean nuclear area was significantly larger in the REC than in the NED group (44 microm2 versus 36 microm2; P = .006). Mitotic count was significantly higher in REC than NED tumors (mean of 4.8 versus 1.7; P = .004). S-phase fraction and ploidy did not predict outcome: neither did nucleolar organizer region numbers and area per cell, or p53 overexpression. Cellular atypia and mitotic count may help in determining the prognosis of adult granulosa tumors of the ovary. The histochemical parameters evaluated did not provide additional information.

Effects of estrone sulfate alone or with medroxyprogesterone acetate on serum lipoprotein levels in postmenopausal women.

OBJECTIVE: To determine the effects of estrone sulfate alone or with different doses of medroxyprogesterone acetate on serum lipid and lipoprotein levels. METHODS: A multicenter, double-masked, randomized trial for 1 year involved 682 postmenopausal women, aged 53.8 +/- 0.2 years (mean +/- standard deviation) with intact uteri. Subjects received fixed daily doses of 0.625 mg of estrone sulfate and one of the following regimens: placebo; 2.5 mg daily of medroxyprogesterone acetate; 5 mg daily of medroxyprogesterone acetate; or 10 mg of medroxyprogesterone acetate for the first 12 days of each 28-day cycle. Fasting lipid and lipoprotein levels were measured at baseline and weeks 12, 16, 24, 30, 36, and 52 of treatment. Absolute mean changes from baseline were determined by paired t test, and treatment effects were determined by analysis of variance. RESULTS: Total cholesterol levels decreased significantly (P <.05) from baseline in all study groups; however, reduction was significantly greater (P <.001) in the 2.5-, 5-, and 10-mg groups (-13.3%, -15.2%, and -14.1%) than in the placebo group (-4.9%). Low-density lipoprotein cholesterol levels decreased significantly and equally in all groups (-10.1% to -12.3%). High-density lipoprotein cholesterol levels increased by 3.2% with unopposed estrogen (P <.05) and did not change from baseline with combined therapy. Triglyceride and very low-density lipoprotein cholesterol levels increased by 13.4% and 2.7%, respectively, in the placebo group, did not change in the 2.5-mg group, decreased by 10.2% and 2.0% and by 11.4% and 2.2% in the 5- and 10-mg groups, respectively (P <.05). CONCLUSION: Estrone sulfate at the daily dose of 0.625 mg alone or with medroxyprogesterone acetate significantly improved lipoprotein levels. Combined therapy with medroxyprogesterone acetate and estrone sulfate was associated with statistically significantly greater reduction in total cholesterol and statistically significantly less increase in triglyceride levels than unopposed estrone sulfate therapy.

Premenstrual exacerbations of mood disorders.

Premenstrual exacerbation of mood disorders has received little attention, despite the recent interest in premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). Differentiating between PMDD/PMS and other disorders, which worsen premenstrually, is a poorly understood diagnostic challenge. Controversy also focuses on a possible coexistence of PMDD and other mood disorders. This review discusses the differences between mood-disorder exacerbations and premenstrual disorders, evidence for premenstrual magnification of mood disorders, and possible mechanisms for these variations as well as clinical implications.

Sublingual administration of micronized estradiol and progesterone, with and without micronized testosterone: effect on biochemical markers of bone metabolism and bone mineral density.

OBJECTIVES: The purpose of this investigation was to evaluate the relative efficacy of the sublingual administration of micronized estradiol (E2), progesterone (P4), and testosterone (T) on bone mineral density and biochemical markers of bone metabolism. DESIGN: In this double-blind, prospective study, postmenopausal women were randomly assigned to one of four treatment groups: hysterectomized women were assigned to either 1) micronized E2 (0.5 mg) or 2) micronized E2 (0.5 mg) + micronized T (1.25 mg). Women with intact uteri were assigned to either 3) micronized E2 (0.5 mg) + micronized P4 (100 mg) or 4) micronized E2 (0.5 mg) + micronized P4 (100 mcg) + micronized T (1.25 mg). For the purpose of this study, the four treatment groups were combined into two groups for all comparisons. The E2 and E2+P4 groups were combined into the HRT alone group (n=30), and the E2+T and E2+P4+T groups were combined into the HRT + T group (n=27). Hormones were administered sublingually as a single tablet twice a day for 12 months. Bone mineral density was measured in the anterior-posterior lumbar spine and total left hip via dual energy x-ray absorptiometry. Bone metabolism was assessed via serum bone-specific alkaline phosphatase and urinary deoxypyridinoline and cross-linked N-telopeptide of type I collagen, both normalized to creatinine. Data were analyzed via a repeated measures analysis of variance and a Student's t test (alpha=0.05). RESULTS: The subjects were of similar age (54.0 +/- 0.8 years), height (64.0 +/- 0.3 in), weight (157.6 +/- 4.2 lb), and had similar baseline follicle-stimulating hormone (66.4 +/- 3.2 mIU/L), E2 (26.4 +/- 1.5 pg/ml), P4 (0.3 +/- 0.1 ng/ml), total T (19.0 +/- 1.5 ng/dL), and bioavailable T (3.7 +/- 0.3 ng/dL) levels. During therapy, serum levels increased (p < 0.05) for each hormone. Bone mineral density and bone markers at baseline were similar for each treatment group. Bone-specific alkaline phosphatase decreased (p < 0.05) by -14.3 +/- 4.1% in the HRT alone group and by -8.2 +/- 4.6% in the HRT + T group. Deoxypyridinoline levels decreased significantly in the HRT alone and HRT + T groups, - 14.4 +/- 6.8% and -26.9 +/- 7.6%, respectively. Significant reductions (p < 0.05) in cross-linked N-telopeptide of type I collagen were also observed in both groups, -24.4 +/- 6.5% and -39.5 +/- 8.6%, respectively. Bone mineral density in the lumbar spine increased (p < 0.05) by +2.2 +/- 0.5% the HRT alone group and by + 1.8 +/- 0.6% in the HRT + T group. Total hip bone mineral density was maintained in the HRT alone group (+0.4 +/- 0.4%) and increased (p < 0.05) in the HRT + T group (+ 1.8 +/- 0.5%). CONCLUSIONS: Sublingual micronized HRT favorably decreases serum and urine markers of bone metabolism, prevents bone loss, and results in a slight increase in spine and hip bone mineral density. Although the addition of testosterone to HRT for 1 year did not result in added benefit to the spine bone mineral density, it did result in a significant increase in hip bone mineral density. Longer duration of therapy may have further improved these outcomes.

Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thromboelastography.

UNLABELLED: Complex coagulopathies follow cardiopulmonary bypass (CPB) in children. However, objective laboratory data that can be acquired rapidly to guide their management are lacking. Because thromboelastography has proven useful in this regard, we evaluated the use of celite or tissue factor (TF) activation and heparinase modification of blood samples to allow rapid determination of thromboelastogram data in children younger than 2 yr undergoing CPB. Celite or TF activation shortened the initiation of clotting and, thus, the time required for the important thromboelastogram alpha and maximum amplitude values to begin evolving. Although thromboelastogram alpha and maximum amplitude values were increased with these activators, correlations persisted between platelet count or fibrinogen level and each of these values. The additional use of heparinase allowed thromboelastograms to be obtained during CPB with values not different from those obtained without heparinase after protamine administration. Therefore, celite- or TF-activated, heparinase-modified thromboelastograms begun during CPB allow objective data to be available by the conclusion of protamine administration to help restore hemostasis after CPB in children. Thromboelastography identified transient fibrinolysis during CPB in some children that resolved by the conclusion of protamine administration. Future investigations of the effectiveness of modified thromboelastography-guided coagulopathy management after CPB in children are needed. IMPLICATIONS: Thromboelastography is useful in assessing the coagulopathies that follow cardiopulmonary bypass in children. Modifying blood samples with celite or tissue factor and heparinase allows thromboelastography begun before the termination of cardiopulmonary bypass to become a rapid point-of-care monitor to provide objective data for guiding blood component therapy to manage these coagulopathies.

Modified Fontan without use of cardiopulmonary bypass.

BACKGROUND: Direct cavopulmonary connection using an extracardiac conduit has a number of theoretical advantages in the staged management of children with single ventricular congenital heart defects. With appropriate planning, completion Fontan using an extracardiac connection may be accomplished without the use of cardiopulmonary bypass. METHODS: From January 1995 to October 1997, 32 consecutive patients underwent completion Fontan using an extracardiac cavopulmonary connection. Twenty-one of these patients had completion Fontan without the use of cardiopulmonary bypass (No CPB group). Their postoperative outcome was retrospectively compared with a second group of 11 patients who underwent completion Fontan with an extracardiac conduit with the use of cardiopulmonary bypass. RESULTS: There was no operative or hospital mortality in either group. Early postoperative hemodynamics appear to be significantly improved in the No CPB group. Transfusion of cryoprecipitate and platelets was significantly less in the group without the use of cardiopulmonary bypass (p = 0.026, p < 0.001, respectively). Review of the most recent 12 patients also demonstrated a substantially shorter extubation time and intensive care unit stay. The length of hospital stay was significantly shorter (p = 0.036). CONCLUSIONS: Completion Fontan without the use of cardiopulmonary bypass results in improved immediate postoperative hemodynamics, and decreased use of blood and blood products. The most recent group appears to demonstrate a more rapid recovery time and shorter hospital stay (p = 0.036).

Comparison of A68 levels in Alzheimer diseased and non-Alzheimer's diseased brain by two ALZ50 based methods.

A total of 61 human brain specimens were analyzed with both ELISA and Western Blot using the ALZ50 monoclonal antibody. The brain specimens included: Alzheimer's Disease (AD, n=31), AD/Down's (n=2), Normal (n=14), Parkinson's Disease (n=7), Huntington's chorea (n=2), Wernicke-Korsakov's Encephalopathy (n=3), and Motor Neuron Disease (n=2). The non-AD cases (n=28) had no detectable A68 by ELISA, and showed no A68 bands by Western blot. The AD cases (n=33), all were positive for A68 by the ELISA, but only 31 of 33 had visible A68 band by Western blot. Additionally, a method for solubilization of A68 is reported.

Lessons learned about research on premenstrual syndrome.

We discuss specific problems in implementing research to evaluate exercise treatment for premenstrual syndrome (PMS). Modifications of lifestyle, such as implementing exercise regimens, frequently are recommended as treatment for PMS, but evidence supporting this treatment is largely anecdotal. Originally, we designed a study to examine the effects of physical exercise on the symptoms of PMS. Despite initial enthusiasm, the majority of participants dropped out before beginning the active intervention segment of the study. This unexpected attrition resulted in a review of methodology, including recruitment and study design, in an attempt to understand factors related to research on exercise-based treatments of PMS so future researchers would be cognizant of the obstacles inherent in such research. Such understanding will allow research to advance more efficiently by enabling investigators to avoid the pitfalls we identified.

Benzofuran based PDE4 inhibitors.

Replacement of the 3,4-dialkoxyphenyl substructure common to a number of PDE4 inhibitors with a 2-alkyl-7-methoxybenzofuran unit is described. This substitution can result in either enhancement or substantial reductions in PDE4 inhibitory activity depending on the system to which it is applied. An in vitro SAR study of a potent series of 4-(2-heteroaryl-ethyl)-benzoiurans 26 is also presented.