A pre-post performance comparison of the long head of the biceps brachii muscle oxygenation in young baseball pitchers.

AIM: The role of the long head of the biceps brachii (LHBB) is vital in maintaining stability of the glenohumeral joint during baseball pitching. Unfortunately the impact of extended pitching on the ability of the LHBB to maintain its function is not currently known. Thus, the purpose of this study was to examine the magnitude of muscle oxyhemoglobin saturation in the biceps brachii, indicated as tissue saturation index (TSI%), before and following an extended pitching performance. METHODS: Data describing the magnitude of TSI% in the long head of the biceps brachii (LHBB) were collected from 20 pitchers (12.5 ± 2.1 years; 151.2 ± 11 cm; 46.7 ± 11.4 kg). TSI% was determined using a wireless muscle oximeter based on near-infrared spectroscopy (NIRS). The oximeter utilized in this study measured oxy, de-oxy, and total hemoglobin as well as tissue saturation. RESULTS: Results revealed that at the conclusion of the simulated game, participants experienced an 11.8% decrease in TSI% at contraction onset (P<0.05), a 5.9% decrease in TSI% at contraction offset (P<0.05), but no difference in TSI% utilized throughout the 5 s isometric contraction. Participants demonstrated a 5.9% decrease in change score for TSI% following the conclusion of the simulated game which did not differ significantly when compared to the beginning of the simulated game (P>0.05). CONCLUSION: These results indicate that young pitchers are not at risk of decreased LHBB function due to lower TSI%. However, the observation of significantly lower levels associated with TSI% following the simulated game reveal that further study into these parameters is warranted in older pitchers as they commonly throw greater than 85 pitches.

Review of intravenous immunoglobulin replacement therapy trials for primary humoral immunodeficiency patients.

An available supply of intravenous immunoglobulin (IVIG) is essential for individuals with primary humoral immunodeficiency. A shortage in 1997 prompted the Food and Drug Administration (FDA) to revise guidelines for the licensure, production, and distribution of new IVIG products, including the standardization of United States clinical trials regarding endpoints for safety, efficacy, and pharmacokinetics. The following review is intended to present current information and results of clinical trials in patients with primary immunodeficiency treated with IVIG products currently licensed or awaiting licensure in the United States. The data presented are compiled from published clinical trials and prescribing information generated by manufacturers.

Steer responses to feeding soybean hulls and steroid hormone implantation on toxic tall fescue pasture.

Crossbred steers were grazed in the spring and early summer on endophyte-infected (Neotyphodium coenophialum), Kentucky-31 tall fescue (Lolium arundinaceum) pastures to evaluate effects and interactions of feeding pelleted soybean hulls (PSBH) and steroid hormone implants (SHI) on steer performance, serum prolactin, and hair coat ratings (HCR). Steers were stratified by BW for assignment to six 3.0-ha toxic tall fescue pastures. With or without daily PSBH feeding, treatments were assigned randomly to pastures as the main plot treatment in a split-plot design. Pelleted soybean hulls were group-fed to provide 2.3 kg(steer·d(-1)) (as fed). With or without SHI (200 mg of progesterone and 20 mg of estradiol) treatments were randomly assigned as the subplot treatment to 2 steer subgroups within each pasture. Sixty-four steers were grazed for 77 d in 2007, and 60 steers were grazed for 86 d in 2008. Pasture forage mass declined linearly over time, but the rate of decline was greater (P = 0.001) in 2007 than in 2008. Pasture forage mass was never below 2,300 kg of DM/ha in either year. Average daily gain for steers on the combined PSBH and SHI treatments was greater (P < 0.01) than for those on the PSBH-only, SHI-only, and control (no SHI, no PSBH) treatments. Average daily gain for the PSBH-only steers was greater (P < 0.01) than for SHI-only and control steers and tended (P = 0.063) to be greater for SHI-only than for control steers. Steroid implants did not affect (P = 0.826) serum prolactin concentrations; however, prolactin concentrations in PSBH steers, with or without SHI, were increased (P = 0.01) 2-fold over SHI-only and control steers. Feeding PSBH and SHI treatments both reduced (P < 0.05) the percentage of steers with rough HCR, and a greater percentage of steers fed PSBH tended (P < 0.076) to have sleek hair coats. An economic analysis was conducted, which determined that costs of additional ADG with PSBH feeding were below breakeven costs over a wide range of PSBH costs and cattle prices. Breakeven costs for PSBH-only treatment for a range of cattle prices of $1.80 to $2.40/kg of BW were less than $120/t, whereas with PSBH feeding combined with SHI the breakeven cost was less than $240/t. Results indicate that steers grazing endophyte-infected tall fescue can be fed PSBH and implanted with steroid hormones to cost effectively increase ADG and that feeding PSBH can increase serum prolactin concentrations and induce some shedding of rough hair coats.

MsrA protects cardiac myocytes against hypoxia/reoxygenation induced cell death.

Reactive oxygen species (ROS) are critical in tissue responses to ischemia-reperfusion. The enzyme methionine sulfoxide reductase-A (MsrA) is capable of protecting cells against oxidative damage by reversing damage to proteins caused by methionine oxidation or by decreasing ROS through a scavenger mechanism. The current study employed adenovirus mediated over-expression of MsrA in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation in this tissue. Cells were transduced with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation. Apoptotic cell death was decreased by greater than 45% in cells over-expressing MsrA relative to cells transduced with a control virus. Likewise total cell death as determined by levels of LDH release was dramatically decreased by MsrA over-expression. These observations indicate that MsrA is protective against hypoxia/reoxygenation stress in cardiac myocytes and point to MsrA as an important therapeutic target for ischemic heart disease.

Mutation in the beta-tubulin signature motif suppresses microtubule GTPase activity and dynamics, and slows mitosis.

We introduced a threonine-to-glycine point mutation at position 143 in the "tubulin signature motif" 140Gly-Gly-Gly-Thr-Gly-Ser-Gly146 of Saccharomyces cerevisiae beta-tubulin. In an electron diffraction model of the tubulin dimer, this sequence comes close to the phosphates of a guanine nucleotide bound in the beta-tubulin exchangeable E site. Both the GTP-binding affinity and the microtubule (MT)-dependent GTPase activity of tubulin isolated from haploid tub2-T143G mutant cells were reduced by at least 15-fold, compared to tubulin isolated from control wild-type cells. The growing and shortening dynamics of MTs assembled from alphabeta:Thr143Gly-mutated dimers were also strongly suppressed, compared to control MTs. The in vitro properties of the mutated MTs (slower growing and more stable) are consistent with the effects of the tub2-T143G mutation in haploid cells. The average length of MT spindles in large-budded mutant cells was only 3.7 +/- 0.2 microm, approximately half of the size of MT arrays in large-budded wild-type cells (average length = 7.1 +/- 0.4 microm), suggesting that there is a delay in mitosis in the mutant cells. There was also a higher proportion of large-budded cells with unsegregated nuclei in mutant cultures (30% versus 12% for wild-type cells), again suggesting such a delay. The results show that beta:Thr143 of the tubulin signature motif plays an important role in GTP binding and hydrolysis by the beta-tubulin E site and support the idea that tubulins belong to a family of proteins within the GTPase superfamily that are structurally distinct from the classic GTPases, such as EF-Tu and p21(ras). The data also suggest that MT dynamics are critical for MT function in yeast cells and that spindle MT assembly and disassembly could be coordinated with other cell-cycle events by regulating beta-tubulin GTPase activity.

The natural history of recovery following sudden cardiac arrest and internal cardioverter-defibrillator implantation.

The purposes of this review are to 1) summarize current knowledge regarding the "natural history of recovery" (physical functioning, psychological adjustment, and neurologic impairments) following sudden cardiac arrest and internal cardioverter-defibrillator implantation over the first year; and 2) discuss the implications for the development of nursing intervention programs based on the natural history of recovery. The natural history serves as a basis for understanding the recovery experiences of sudden cardiac arrest survivors as well as determining how intervention programs might help the most.

Theoretical development of nursing interventions for sudden cardiac arrest survivors using social cognitive theory.

This article discusses the theoretical development of a nursing intervention program to enhance recovery over the first year following sudden cardiac arrest. Concepts from social cognitive theory and domains of concern following sudden cardiac arrest underpin a tailored and standardized nursing intervention. The nursing intervention program is designed for delivery by means of telephone and through the mail. Testing of the nursing intervention program is underway using a clinical trial design.

Mutagenesis of beta-tubulin cysteine residues in Saccharomyces cerevisiae: mutation of cysteine 354 results in cold-stable microtubules.

Cysteine residues play important roles in the control of tubulin function. To determine which of the six cysteine residues in beta-tubulin are critical to tubulin function, we mutated the cysteines in Saccharomyces cerevisiae beta-tubulin individually to alanine and serine residues. Of the twelve mutations, only three produced significant effects: C12S, C354A, and C354S. The C12S mutation was lethal in the haploid, but the C12A mutation had no observable phenotype. Based on interactive views of the electron crystallographic structure of tubulin, we suggest that substitution of serine for cysteine at this position has a destabilizing effect on the interaction of tubulin with the exchangeable GTP. The two C354 mutations, although not lethal, produced dramatic effects on microtubules and cellular processes that require microtubules. The C354 mutant cells had decreased growth rates, a slowed mitosis, increased resistance to benomyl, and impaired nuclear migration and spindle assembly. The C354A mutation produced a more severe phenotype than the C354S mutation: the haploid cells had chromosome segregation defects, only 50% of cells in a culture were viable, and a significant percentage of the cells were misshapened. Cytoplasmic microtubules in the C354S and C354A cells were longer than in the control strain and spindle structures appeared shorter and thicker. Both cytoplasmic and spindle microtubules in the two C354 mutants were extremely stable to cold temperature. After 24 h at 4 degrees C, the microtubules were still present and, in fact, very long and thick tubulin polymers had formed. Evidence exists to indicate that the C354 residue in mammalian tubulin is near the colchicine binding site and the electron crystal structure of tubulin places the residue at the interface between the alpha- and beta-subunits. The sulfhydryl group is situated in a polar environment, which may explain why the alanine mutation is more severe than the serine mutation. When the C12S and the two C354 mutations were made in a diploid strain, the mutated tubulin was incorporated into microtubules and the resulting heterozygotes had phenotypes that were intermediate between those of the mutated haploids and the wild-type strains. The results suggest that the C12 and C354 residues play important roles in the structure and function of tubulin.

Testing the effectiveness of converting patients to long-acting antianginal medications: The Quality of Life in Angina Research Trial (QUART).

OBJECTIVE: Our purpose was to test the hypothesis that converting patients with stable angina to long-acting antianginal medications would improve their functional status, symptom control, treatment satisfaction, and quality of life. METHODS AND RESULTS: A single-blind randomized trial of 100 patients with stable coronary artery disease was performed in the outpatient clinic of a Veterans Affairs Health System. Outpatients with chronic stable angina taking at least 2 antianginal medications were studied. Patients were randomized to one of two treatments: optimal adjustment of their usual antianginal medications or conversion to solely long-acting medications (long-acting diltiazem +/- nitroglycerin patches +/- atenolol) with subsequent optimization. The primary outcome was the 3-month change in Seattle Angina Questionnaire scores. Although no differences in physical limitation scores were noted, patients randomized to receive long-acting medications had improved symptom control (3-month improvement in anginal stability [19.1 vs 5.6, P =.02] and anginal frequency [17.8 vs 5.5, P =.006]), more treatment satisfaction (3-month improvement of 8.2 vs 3.0, P =.057), and better quality of life (3-month improvement of 11.2 vs 5.6, P =.09) compared with patients whose pretrial medications were optimized. The improvement in symptom control was statistically significant. CONCLUSION: Converting patients with chronic, stable angina to long-acting antianginal medications resulted in substantial improvements in symptom control with a trend toward better treatment satisfaction and quality of life.

Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis.

Nitric oxide (NO) induces apoptosis in cardiac myocytes through an oxidant-sensitive mechanism. However, additional factors appear to modulate the exact timing and rate of NO-dependent apoptosis. In this study, we investigated the role of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] 1/2, and p38MAPK) in NO-mediated apoptotic signaling. The NO donor S:-nitrosoglutathione (GSNO) induced caspase-dependent apoptosis in neonatal rat cardiac myocytes, preceded by a rapid (<10-minute) and significant (approximately 50-fold) activation of JNK1/2. Activation of JNK was cGMP dependent and was inversely related to NO concentration; it was maximal at the lowest dose of GSNO (10 micromol/L) and negligible at 1 mmol/L. NO slightly increased ERK1/2 beginning at 2 hours but did not affect p38MAPK activity. Inhibitors of ERK and p38MAPK activation did not affect cell death rates. In contrast, expression of dominant-negative JNK1 or MKK4 mutants significantly increased NO-induced apoptosis at 5 hours (56.77% and 57.37%, respectively, versus control, 40.5%), whereas MEKK1, an upstream activator of JNK, sharply reduced apoptosis in a JNK-dependent manner. Adenovirus-mediated expression of dominant-negative JNK1 both eliminated the rapid activation of JNK by NO and accelerated NO-mediated apoptosis by approximately 2 hours. These data indicate that NO activates JNK as part of a cytoprotective response, concurrent with initiation of apoptotic signaling. Early, transient activation of JNK serves both to delay and to reduce the total extent of apoptosis in cardiac myocytes.

Dietary exposures to food contaminants across the United States.

Food consumption is an important route of human exposure to pesticides and industrial pollutants. Average dietary exposures to 37 pollutants were calculated for the whole United States population and for children under age 12 years by combining contaminant data with food consumption data and summing across food types. Pollutant exposures were compared to benchmark concentrations, which are based on standard toxicological references, for cancer and noncancer health effects. Average food ingestion exposures for the whole population exceeded benchmark concentrations for arsenic, chlordane, DDT, dieldrin, dioxins, and polychlorinated biphenyls, when nondetects were assumed to be equal to zero. For each of these pollutants, exposure through fish consumption accounts for a large percentage of food exposures. Exposure data for childhood age groups indicated that benchmark concentrations for the six identified pollutants are exceeded by the time age 12 years is reached. The methods used in this analysis could underestimate risks from childhood exposure, as children have a longer time to develop tumors and they may be more susceptible to carcinogens; therefore, there may be several additional contaminants of concern. In addition, several additional pollutants exceeded benchmark levels when nondetects were assumed to be equal to one half the detection limit. Uncertainties in exposure levels may be large, primarily because of numerous samples with contaminant levels below detection limits.

Outpatient nursing case management for cardiovascular disease.

Case management has been an effective treatment model for maintaining costs while preserving quality of care for vulnerable populations who are frequent care users. Nursing case management has been effective in improving health outcomes in chronically ill populations. Specifically, nurse practitioner care has been as effective, and in some areas, more effective in managing chronic health problems of patients than care provided by physicians. Cardiovascular disease is a chronic condition, often accompanied by long-term symptoms and disability, that is prevalent in the United States population. Outpatient nursing case management for chronic health problems associated with cardiovascular disease is posited as a model for a heavily used system that maintains quality of care in this group.

Beware of contaminating mouse cells in human xenografts from nude mice.

Human tumor xenografts in nude mice are widely utilized model system for the transplantation of human surgical specimens and human established cell lines. Gene expression studies are often carried out in these model systems. With an increasing use of PCR based analyses, the extreme sensitivity of this technique poses a serious challenge with regards to the extent of contaminating host mouse cells in the human tumor xenografts. These xenografts are never free of host cell contamination. We detected mouse estrogen receptor expression in several human tumor xenografts using RT-PCR demonstrating that precaution is necessary when utilizing PCR based analyses in human tumor xenografts. A cytologically based methodology which distinguishes human versus mouse cells will be more suitable for ER expression studies using human xenograft models. Both (1) in situ hybridization using human probe and (2) immunocytochemistry using a monoclonal antibody directed against human cytokeratin have been used successfully to distinguish human cells versus host mouse cells in human xenografts in nude mice. Immunostaining of ER can then be utilized to determine the expression pattern of ER in the transplanted human cells.

MR imaging in patients with nipple discharge: initial experience.

PURPOSE: To investigate the potential of magnetic resonance (MR) imaging in patients with nipple discharge. MATERIALS AND METHODS: Between February 1992 and December 1998, 23 patients with nipple discharge underwent contrast material-enhanced MR imaging at 1.5 T. Mammographic findings were negative in 22 of 23 patients and revealed asymmetry in one patient. Galactography was attempted in two patients, with negative findings in one patient and no success in the other. Fifteen of 23 patients underwent excisional biopsy-seven of 15 with MR imaging-guided localization, and one of 15 with mammographic localization. Eight of 23 patients were followed up clinically (range, 7-24 months; mean, 20 months). RESULTS: In 11 of the 15 (73%) patients who underwent excisional biopsy, MR imaging findings correlated with histopathologic findings. MR imaging demonstrated four of six benign papillomas and one of two fibroadenomas as circumscribed, enhancing subareolar masses. Findings of one MR imaging examination were negative, and benign tissue was found at excisional biopsy. MR imaging findings were suspicious in six of the seven patients with excisional biopsy findings of malignancy (regional enhancement [n = 2], ductal enhancement [n = 2], peripherally enhancing mass [n = 1], and spiculated mass [n = 1]). In one of the seven patients, a benign-appearing intraductal mass was identified at MR imaging; excisional biopsy revealed a benign papilloma with an adjacent focus of DCIS. CONCLUSION: MR imaging can help identify both benign and malignant causes of nipple discharge. It potentially offers a noninvasive alternative to galactography.

Domains of nursing intervention after sudden cardiac arrest and automatic internal cardioverter defibrillator implantation.

PURPOSE: The purpose of the study was to explore individual and family experiences after sudden cardiac arrest and automatic internal cardioverter defibrillator implantation during the first year of recovery. This report specifically addresses the domains of concern expressed and helpful strategies used by participants that are relevant to the development of future intervention programs. DESIGN: A grounded theory approach was used to gain an understanding of areas of concern of sudden cardiac arrest survivors and families that could be used when designing future nursing interventions. Semistructured interviews were conducted with both sudden cardiac arrest survivors and 1 family member each at 5 points during the first year of recovery (hospitalization; 1, 3, 6, and 12 months after hospitalization). Participants were asked to identify those specific areas that most concerned them and that they would like assistance with during the first year. A total of 150 interviews were conducted with 176 hours of data generated. SETTING: The study focused on 10 northwest urban community medical centers and participants' homes within a 50-mile driving distance from the medical centers. SAMPLE: The sample included 15 first-time sudden cardiac arrest survivors (13 men and 2 women) and 1 family member each between the ages of 31 and 72 years. RESULTS: Domains of concern identified by participants that can be used to design future nursing intervention programs included preventive care, dealing with automatic internal cardioverter defibrillator shocks, emotional challenges, physical changes, activities of daily living, partner relationships, and dealing with health care providers. Suggestions of helpful strategies used by participants during the first year are outlined. IMPLICATIONS: Domains of concern and helpful strategies identified by participants provide a framework for the development and testing of nursing intervention programs to enhance recovery following sudden cardiac arrest for survivors and their families.

Steady-state kinetic analysis of human ubiquitin-activating enzyme (E1) using a fluorescently labeled ubiquitin substrate.

We report the synthesis of fluorescently labeled ubiquitin (Ub) and its use for following ubiquitin transfer to various proteins. Using Oregon green (Og) succinimidyl ester, we prepared a population of Ub mainly labeled by a single Og molecule; greater than 95% of the Og label is associated with Lys 6 of Ub. We demonstrate that Og-Ub is efficiently accepted by Ub-utilizing enzymes, such as the human ubiquitin-activating enzyme (E1). We used this fluorescent substrate to follow the steady-state kinetics of human E1-catalyzed Ub-transfer to the ubiquitin-carrier enzyme Ubc4. In this reaction, E1 uses three substrates: ATP, Ubc4, and Ub. The steady-state kinetics of Og-Ub utilization by E1 is presented. We have also used analytical ultracentrifugation methods to establish that E1 is monomeric under our assay condition (low salt) as well as under physiological condition (150 mM NaCl).

Estrogen and progesterone receptors can be maintained in normal human breast epithelial cells in primary culture and after transplantation into nude mice.

The estrogen and progesterone receptor expression was determined in breast epithelial cells from reduction mammoplasty specimens. Only a subset of the luminal epithelial cell population was found to be positive for these receptors. When these cells were subsequently cultured in 3-dimensional collagen gel system (in vitro model) or transplanted into nude mice (in vivo model), the cells retained their ability to express both receptors in these experimental systems. The maintenance of primary normal human breast epithelial cells expressing the estrogen and progesterone receptors in experimental systems has not been reported previously.

Mortality of horn fly larvae (Diptera: Muscidae) in bovine dung supplemented with ergotamine and N-formyl loline.

Dung-dwelling larvae of ectoparasites of livestock such as the horn fly, Hematobia irritans (L.), may be exposed to > or = 1 different alkaloid species in dung from animals ingesting herbage of the tall fescue (Festuca arundinacea Schreb.)--endophyte association (Neotyphodium coenophialum (Morgan-Jones & W. Gams) Glenn, Bacon & Hanlin comb. nov.). First-instar horn flies were exposed to bovine dung supplemented with up to 50 microM each of N-formyl loline and ergotamine tartrate in factorial combination. In the absence of ergotamine tartrate, N-formyl loline caused a linear decline in the number of pupae recovered, and probit analysis indicated an LC50 of 36 microM. In the absence of N-formyl loline, significant quadratic responses of larvae to ergotamine tartrate were established, and probit analysis indicated a LC50 of 34 microM. An interaction (P < 0.001) was found between the 2 alkaloids for larval survival. This interaction showed that ergotamine tartrate moderated the toxicity of N-formyl loline and indicates that a membrane-bound receptor may be involved. There was no evidence of carryover of effects of alkaloids on subsequent stages of development or expressed as abnormalities of pupae or adults. Interactions between alkaloids probably are involved in other plant-herbivore relationships of endophyte-infected grasses.