Exercise-Induced Dyspnea in Collegiate Athletes: Are We Missing the Diagnosis?

OBJECTIVES: Exercise-induced dyspnea (EID) can disrupt an athlete's participation and performance in their given sport. Differential diagnosis of EID is often completed using subjective report and may be inaccurate, therefore increasing the frustration and stress of the athlete. This nonexperimental research study was used to determine prevalence of EID and related respiratory symptoms in athletes at a small, Division I university. METHODS: An anonymous survey was provided to athletes at Murray State University as they registered for participation in sports for the 2020-2021 school year. Data from this survey was analyzed as to reported physician-given diagnosis of a respiratory disorder as well as reported symptoms of EID. RESULTS: Results showed that athletes with a physician-given diagnosis often did not report symptoms or responses to medications that support that diagnosis. Additionally, athletes frequently reported symptoms of EID without a formal diagnosis of a respiratory disorder. CONCLUSIONS: These findings provide preliminary insight and pilot data that may be used to understand the prevalence of EID in collegiate athletes and the need for improved methods of diagnosis for etiologies of EID.

Struggling to Breathe: Inspiratory Muscle Training in Adolescent Athletes.

OBJECTIVE: Dyspnea is a primary characteristic of exercise-induced laryngeal obstruction and prevents individuals from inhaling and exhaling without effort. This single subject research study investigated the effects of inspiratory muscle training (IMT) on exercise-induced symptoms characteristic of exercise-induced laryngeal obstruction in adolescent athletes. METHODS: Five weeks of IMT was provided to five adolescent athletes, four females and one male, aged 10 to 16. Variables that were measured prior to, during, and after completion of IMT program included maximum phonation time, maximum perceived breathlessness, duration of running, and quality of life regarding dyspnea. RESULTS: Results showed a reduction in maximum perceived breathlessness as well as a significant increase in maximum phonation time across participants. The majority of participants rated their quality of life regarding dyspnea as significant improved after IMT. CONCLUSIONS: These findings contribute to the increasing body of literature investigating the use of alternative therapy strategies for treatment of symptoms of exercise-induced laryngeal obstruction in adolescent athletes.

Effects of oxygen on the antigenic landscape of prostate cancer cells.

BACKGROUND: Use of allogeneic cancer cells-based immunotherapy for treatment of established prostate cancer (PCa) has only been marginally effective. One reason for failure could stem from the mismatch of antigenic signatures of vaccine cells and cancer in situ. Hence, it is possible that vaccine cells expressed antigens differently than tumor cells in situ. We hypothesized that cells grown in vitro at low oxygen tension (pO2) provide a better antigen match to tumors in situ and could reveal a more relevant antigenic landscape than cells grown in atmospheric pO2. METHODS: We tested this hypothesis by comparing PCa cells propagated at pO2 = 2 kPa and 20 kPa. To identify potential tumor-associated antigens (TAAs), we prepared PCa cell lysates, resolved them by two-dimensional electrophoresis and immunoblotting using spontaneous antibodies from plasma derived from PCa patients and control subjects. Antibody-labeled spots were analyzed by MALDI-TOF mass spectrometry and validated by ELISA. We selected hypoxia-regulated HSP70 and hnRNP L and hypoxia-independent HSP60 and determined the frequency of plasma samples reacting with these molecules. RESULTS: Frequency of HSP60-reactive plasma was low in healthy controls [1.3 % (1/76)], while it was elevated in PCa patients [13.0 % (7/54); p < 0.05]. These data suggest a humoral immune response to HSP60 in PCa. Levels of autoantibodies to HSP70 did not differ from healthy controls [3.7 % (2/54)] in PCa patients [5.3 % (2/38)]. Similarly, hnRNP L autoantibodies did no differ between healthy controls [6.1 % (3/49)] and PCa patients [5.3 % (2/38)]. CONCLUSIONS: Overall our results suggest the value of hypoxia as a modifier of the cellular and antigenic landscape of PCa cells. By modifying the immune reactivity of PCa cells in culture, manipulation of pO2 can be proposed as a new avenue for improving diagnosis, prognosis and immunotherapy for PCa.

Damage modeling and statistical analysis of optics damage performance in MJ-class laser systems.

Modeling the lifetime of a fused silica optic is described for a multiple beam, MJ-class laser system. This entails combining optic processing data along with laser shot data to account for complete history of optic processing and shot exposure. Integrating with online inspection data allows for the construction of a performance metric to describe how an optic performs with respect to the model. This methodology helps to validate the damage model as well as allows strategic planning and identifying potential hidden parameters that are affecting the optic's performance.

Prognostic value of discs large homolog 7 transcript levels in prostate cancer.

Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia-regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p ≤ 0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP.

Age-dependent response of murine female bone marrow cells to hyperbaric oxygen.

Consequences of age on the effects of hyperbaric oxygen (HBO) on bone marrow (BM) derived stem cells and progenitors (SCPs) are largely unknown. We treated 2- and 18-month old C57BL/6 female mice by HBO. Hematopoietic stem cells and progenitors, enumerated as colony-forming units in culture, were doubled only in peripheral leukocytes and BM cells of young mice receiving HBO. In old mice colony-forming unit fibroblast numbers, a measure of mesenchymal stromal cells (MSCs) from BM, were high but unaffected by HBO. To further explore this finding, in BM-MSCs we quantified the transcripts of adipocyte early-differentiation genes peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein-ß and fatty-acid binding protein 4; these transcripts were not affected by age or HBO. However, osteoblast gene transcripts runt-related transcription factor 2, osterix (OSX) and alkaline phosphatase (AP) were twofold to 20-fold more abundant in MSCs from old control mice relative to those of young control mice. HBO affected expression of osteoblast markers only in old MSCs (OSX gene expression was reduced by twofold and AP expression was increased threefold). Our data demonstrate the impact of aging on the response of BM SCPs to HBO and indicate the potentially different age-related benefit of HBO in wound healing and tissue remodeling.

Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo.

Imatinib mesylate (STI571, imatinib) inhibited DNA synthesis in primary human T cells stimulated with allogeneic mature dendritic cells or phytohemagglutinin (PHA) but did not induce apoptosis. The values for the concentration that inhibits 50% (IC50) of T-cell proliferation stimulated by dendritic cells and PHA were 3.9 microM and 2.9 microM, respectively, that is, within the concentration range found in patients treated with imatinib mesylate. Interestingly, imatinib mesylate did not inhibit expression of T-cell activation markers CD25 and CD69, although it reduced the levels of activated nuclear factor-kappaB (NF-kappaB) and changed phosphorylation or protein levels of Lck, ERK1/2, retinoblastoma protein, and cyclin D3. When T cells were washed free of imatinib mesylate, they proliferated in response to PHA, demonstrating that inhibition is reversible. Treatment with imatinib mesylate led to accumulation of the cells in G0/G1 phase of the cell cycle. The in vitro observations were confirmed in vivo in a murine model of delayed-type hypersensitivity (DTH). In mice treated with imatinib mesylate, DTH was reduced in comparison to sham-injected controls. However, the number of splenic T cells was not reduced showing that, similarly to in vitro observations, imatinib mesylate inhibited T-cell response, but did not cause apoptosis. These findings indicate that long-term administration of high-dose imatinib mesylate might affect immunity.

Interpreting and defensively responding to threat: examining appraisals and coping with acquaintance sexual aggression.

Resistance and prevention programming aimed at strengthening women's ability to protect themselves against acquaintance sexual aggression has lacked attention to the cognitive and emotional processes women engage in when encountering such threats. Building upon current theory related to cognitive appraisal and coping processes, this study applies a theoretical model of how women evaluate and respond to sexual aggression by male acquaintances. Two hundred and two college women who had been sexually victimized by male acquaintances responded to a questionnaire that assessed their cognitive appraisals of and emotional and behavioral responses to the incident, in addition to aggression characteristics. Path analytic regression analyses examined theorized relationships among primary and secondary appraisal and emotional response variables in addition to their collective prediction of behavioral responding. The hypothesized model accounted for significant variance in behavioral responding and indicated different patterns of appraisals, emotions, and aggression characteristics predicting women's assertive and diplomatic behavioral responses to their assaults. These findings are consistent with research and theory related to individuals' appraisal of and coping with threatening events. Theoretical and intervention implications for resistance and prevention efforts are discussed.

Pharmacokinetics and metabolism of rimantadine hydrochloride in mice and dogs.

We studied the pharmacokinetics and metabolism of rimantadine hydrochloride (rimantadine) following single-dose oral and intravenous administration in mice and dogs. Absorption of the compound in mice was rapid. Maximum concentrations in plasma occurred at less than 0.5 h after oral administration, and the elimination half-life was 1.5 h. Peak concentrations in plasma following oral administration were markedly disproportional to the dose (274 ng/ml at 10 mg/kg, but 2,013 ng/ml at 40 mg/kg). The bioavailability after an oral dose of 40 mg/kg was 58.6%. Clearance was 4.3 liters/h per kg, and the volume of distribution was 7.6 liters/kg at 40 mg/kg. In contrast to the results observed in mice, absorption of the compound in dogs was slow. Maximum concentrations in plasma occurred at 1.7 h after oral administration, and the elimination half-life was 3.3 h. A further difference was that peak concentrations in plasma were approximately proportional to the dose. Following administration of a single oral dose of 5, 10, or 20 mg/kg, maximum concentrations in plasma were 275,800, and 1,950 ng/ml, respectively. The bioavailability after an oral dose of 5 mg/kg was 99.4%. The clearance was 3.7 liters/h per kg, and the volume of distribution was 13.8 liters/kg at 5 mg/kg. Mass balance studies in mice, using [methyl-14C]rimantadine, indicated that 98.7% of the administered dose could be recovered in 96 h. Less than 5% of the dose was recovered as the parent drug in dog urine within 48 h. Finally, gas chromatography-mass spectrometry studies, done with mouse plasma, identified the presence of two rimantadine metabolites. These appeared to be ring-substituted isomers of hydroxy-rimantadine.

Prescription: office automation.

The mission statement of Minneapolis Children's Medical Center reads, in part, "Mindful of the unique characteristics of children, MCMC's missions is to provide a team of health care professionals attuned to the special needs of the total child, at all ages from prenatal through adolescent, in a uniquely designed facility." Therefore an "open" professional staff, rather than a medical staff, was established consisting of physicians, dentists, and other health professionals with advanced degrees at the master's level or above, including, but not limited to, psychologists, social workers, clinical nurse specialists, chaplains, audiologists, and speech pathologists. This professional staff has grown to 650 members, extremely large for a 122-bed hospital. The professional staff office needed help in managing the volume of information associated with this large staff. To meet that need, in addition to the needs of other hospital areas, MCMC's administration made the decision to purchase office automation equipment and established a committee of hospital-wide users, rather than managerial staff, to survey their own needs, select vendors, and make the final recommendation. The word-processing system selected now maintains 650 physician profiles, each with 44 variables. Whereas prior to automation 25 separate lists needed to be updated each time a professional staff member was either added or deleted, now only individual physician profiles need to be adjusted. Programs were then designed to automate the many reports that must be done. In this paper we propose to describe this selection process and relate how the system developed has streamlined and simplified the work of the professional staff office to enable it to increase its output by over 300% without adding staff.

High-performance liquid chromatographic determination of ethmozin in plasma.

A sensitive, specific high-performance liquid chromatographic procedure was developed for the determination of plasma ethmozin levels. Basic plasma samples were partitioned with methylene chloride. The organic extract was washed with water and then evaporated to dryness under reduced pressure. The residue was redissolved in 0.2 ml of the mobile phase, consisting of hexane-tetrahydrofuran-methanol-water (66:27:6,30:0.7 v/v), and then chromatographed on a microporous silica column. With a variable-wavelength UV detector set at 268 nm, 10 ng of ethmozin/ml of plasma was measured. The utility of the method for human pharmacokinetic studies was demonstrated.

Determination of oxycodone in plasma and identification of a major metabolite.

An electron-capture GLC method is described for oxycodone and its major metabolite, noroxycodone, in plasma and urine. The method involves extraction of the two substances into benzene-isopropranol at pH 10.4, followed by back-extraction into 0.1 N HCl. The acid phase is washed with hexane and made alkaline prior to reextraction into benzene-isopropanol. The solvent is removed by evaporation, and the heptafluorobutyryl derivatives of the test substances are formed. After removal of excess reagent, oxycodone and noroxycodone are quantitated by GLC. The characteristics of both substances, with respect to plasma levels in dogs and analgesic activity in mice, are reported. Isolation of noroxycodone from human urine and its identification by TLC, GLC, and mass spectrometry are described.

Quantitative determination of nalbuphine in plasma using electron-capture detection.

A procedure for the determination of nalbuphine in plasma is presented. The compound and an internal standard are extracted into benzene-2-propanol from plasma at pH 10.4, followed by back-extraction into 0.1 N HCl. After the acid phase is washed with benzene and the compound is reextracted into benzene-2-propanol, the heptafluorobutyryl derivatives are formed and determined using electron-capture GLC. The lower limit of sensitivity is approximately 0.5 ng/ml, and the upper limit of the linear dynamic range is greater than 50 ng/ml. Peak plasma levels of 50 and 150 ng were observed in two dogs 10 and 20 min, respectively, after subcutaneous administration of 1 mg of nalbuphine/kg. Nalbuphine was detectable in plasma 5 hr after administration.