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Jacalyn M GreenDepartment of Biochemistry, Midwestern University, IL, USAAbstract: In January 2012, glucarpidase (Voraxaze®) received approval from the US Food and Drug Administration for intravenous treatment of toxic plasma methotrexate concentrations due to impaired renal clearance. Methotrexate, an antifolate agent, has been used for over 60 years in the treatment of various cancers. High-dose methotrexate has been particularly useful in the treatment of leukemias and lymphomas. However, even with aggressive hydration and urine alkalinization, such regimens can lead to acute renal dysfunction, as indicated by decreases in urine production and concomitant increases in blood urea nitrogen and serum creatinine levels. Because methotrexate is largely excreted by the kidneys, this can greatly potentiate tissue damage. Toxic levels of blood methotrexate can be rapidly and effectively decreased by intravenous administration of glucarpidase. Glucarpidase is a recombinant form of carboxypeptidase G2, a bacterial enzyme that rapidly cleaves methotrexate to form the amino acid glutamate and 2,4-diamino-N10-methylpteroic acid. Catabolites of methotrexate are much less toxic than the parent compound, and are primarily excreted by hepatic mechanisms. Glucarpidase has been available on a compassionate basis since the 1990s, and a variety of case reports and larger clinical trials have demonstrated the safety and efficacy of this drug in patients ranging in age from infants to the elderly and in a variety of races and ethnic groups. Glucarpidase should not be administered within 2 hours of leucovorin, because this agent is a reduced folate which competes with methotrexate for the enzyme and glucarpidase inactivates leucovorin. Side effects of glucarpidase are rare and relatively mild, and include paraesthesia, flushing, nausea, vomiting, pruritus, and headache. Glucarpidase has seen limited use in intrathecal treatment of methotrexate toxicity for which it is also effective. Future applications of this enzyme in chemotherapy continue to be an active area of research.Keywords: glucarpidase, Voraxaze®, carboxypeptidase G2, methotrexate, antifolate, chemotherapy

Costimulation mediated by the CD28 receptor has been shown to play an important role in the development of a vigorous T cell immune response. Nevertheless, CD28-deficient mice can mount effective T cell-dependent immune responses. These data suggest that other costimulatory molecules may play a role in T cell activation. In a search for other costimulatory receptors on T cells, we have characterized a monoclonal antibody (mAb) that can costimulate T cells in the absence of accessory cells. Similar to CD28 antibodies, this mAb, R2/60, was found to synergize with T cell receptor engagement in inducing proliferation. Independent ligation of CD3 and the ligand recognized by R2/60 results in T cell proliferation, suggesting that the two molecules do not have to colocalize to activate the R2/60 costimulatory pathway. R2/60 does not react with CD28, and furthermore, R2/60 costimulates in a CD28-independent fashion since the mAb costimulates T cells from the CD28-deficient mice as well as wild-type mice. Expression cloning of the R2/60 antigen identified the ligand as murine CD43. Together, these data demonstrate that CD43 can serve as a receptor on T cells that can provide CD28-independent costimulation.

As part of the molecular revolution sweeping medicine, comprehensive genomic studies are adding powerful dimensions to medical research. However, their power exposes new regulatory, strategic, and quality assurance challenges for biorepositories. A key issue is that unlike other research techniques commonly applied to banked specimens, nucleic acid sequencing, if sufficiently extensive, yields data that could identify a patient. This evolving paradigm renders the concepts of anonymized and anonymous specimens increasingly outdated. The challenges for biorepositories in this new era include refined consent processes and wording, selection and use of legacy specimens, quality assurance procedures, institutional documentation, data sharing, and interaction with institutional review boards. Given current trends, biorepositories should consider these issues now, even if they are not currently experiencing sample requests for genomic analysis. We summarize our current experiences and best practices at Washington University Medical School, St Louis, MO, our perceptions of emerging trends, and recommendations. [ABSTRACT FROM AUTHOR]

Postnatal depression (PND) impacts on the mother and her partner, the family, mother-baby interaction and on the baby. This review synthesises the evidence from qualitative and quantitative research to determine whether screening for PND is acceptable to women and healthcare professionals. The research literature was systematically searched to retrieve articles available until February 2007. No language or geographical restrictions were applied. Studies were included if the acceptability of PND screening was assessed during the prenatal and postnatal period. Data were synthesised using the textual narrative approach. Fifteen of the 16 eligible studies focused on the acceptability of the Edinburgh Postnatal Depression Scale (EPDS). Screening for PND was generally found to be acceptable to women and healthcare professionals, although aspects of its administration were identified as being important. Specifically, a woman needs to feel comfortable about the screening process if she is to answer the questions honestly. This may be facilitated through forewarning and administration by a trusted person in her own home. Healthcare professionals need to be aware of differing cultural attitudes towards answering the questions, and the ambiguity of the question about self-harm. Further research into the acceptability of strategies other than EPDS is needed. [ABSTRACT FROM AUTHOR]

Objective: This study assessed treatment preferences among low-income Latino patients in public-sector primary care clinics and examined whether a collaborative care intervention that included patient education and allowed patients to choose between medication, therapy, or both would increase the likelihood that patients received preferred treatment.Methods: A total of 339 Latino patients with probable depressive disorders were recruited; participants completed a baseline conjoint analysis preference survey and were randomly assigned to receive the intervention or enhanced usual care. At 16 weeks, a patient survey assessed depression treatment received during the study period. Logistic regression models were constructed to estimate treatment preferences, examine patient characteristics associated with treatment preferences, and examine patient characteristics associated with a match between stated preference and actual treatment received.Results: The conjoint analysis preference survey showed that patients preferred counseling or counseling plus medication over antidepressant medication alone and that they preferred treatment in primary care over specialty mental health care, but they showed no significant preference for individual versus group treatment. Patients also indicated that individual education sessions, telephone sessions, transportation assistance, and family involvement were barrier reduction strategies that would enhance their likelihood of accepting treatment. Compared with patients assigned to usual care, those in the intervention group were 21 times as likely to receive preferred treatment. Among all participants, women, unemployed persons, those who spoke English, and those referred by providers were more likely to receive preferred treatment.Conclusions: Collaborative care interventions that include psychotherapy can increase the likelihood that Latino patients receive preferred care; however, special efforts may be needed to address preferences of working persons, men, and Spanish-speaking patients. [ABSTRACT FROM AUTHOR]

The current investigation examined the potential teleoanticipatory effect on perceptual response during repeated bouts of maximal sprint work. To determine the consistency of ratings of perceived exertion (RPE) increase during identical exercise bouts following variable recovery periods, 16 (8 men, 8 women) participants completed four separate trials of repeated maximal sprinting on 4 separate days utilizing different recovery periods. Following completion of the baseline trial, participants were given variable, counter-balanced recovery periods of 24, 48 and 72 hours, whereupon they repeated the intermittent exercise protocol. To determine the degree of similarity among trials, each individual's rate of RPE progression during each cycle of eight sprints throughout the recovery trials were compared to the rate of progression during the baseline exercise session. A series of 4 (trial) × 3 (cycle of sprints) repeated measures ANOVA were performed to identify significant main effects between trials and among cycles while session RPE was analyzed using one-way repeated measures ANOVA. Fisher's least significant difference post-hoc procedures were performed to identify where significant differences occurred when appropriate. Results revealed an inconsistency in the stability of RPE across repeated bouts of sprint exercise, with at least 50%of individuals having a substantial difference in RPE (i.e. ± 1 unit change) in at least one subsequent trial. These variations in perceptual responses were observed despite a concomitant stability of physiological and performance responses between sessions. Results suggest that rate of RPE increase correspond more closely to increased or decreased physiologic strain than to an anticipatory, feed-forward mechanism following variable recovery durations. [ABSTRACT FROM AUTHOR]

The effect caffeine elicits on endurance performance is well founded. However, comparatively less research has been conducted on the ergogenic potential of anaerobic performance. Some studies showing no effect of caffeine on performance used untrained subjects and designs often not conducive to observing an ergogenic effect. Recent studies incorporating trained subjects and paradigms specific to intermittent sports activity support the notion that caffeine is ergogenic to an extent with anaerobic exercise. Caffeine seems highly ergogenic for speed endurance exercise ranging in duration from 60 to 180 seconds. However, other traditional models examining power output (i.e. 30-second Wingate test) have shown minimal effect of caffeine on performance. Conversely, studies employing sport-specific methodologies (i.e. hockey, rugby, soccer) with shorter duration (i.e. 4-6 seconds) show caffeine to be ergogenic during high-intensity intermittent exercise. Recent studies show caffeine affects isometric maximal force and offers introductory evidence for enhanced muscle endurance for lower body musculature. However, isokinetic peak torque, one-repetition maximum and muscular endurance for upper body musculature are less clear. Since relatively few studies exist with resistance training, a definite conclusion cannot be reached on the extent caffeine affects performance. It was previously thought that caffeine mechanisms were associated with adrenaline (epinephrine)-induced enhanced free-fatty acid oxidation and consequent glycogen sparing, which is the leading hypothesis for the ergogenic effect. It would seem unlikely that the proposed theory would result in improved anaerobic performance, since exercise is dominated by oxygen-independent metabolic pathways. Other mechanisms for caffeine have been suggested, such as enhanced calcium mobilization and phosphodiesterase inhibition. However, a normal physiological dose of caffeine in vivo does not indicate this mechanism plays a large role. Additionally, enhanced Na+/K+ pump activity has been proposed to potentially enhance excitation contraction coupling with caffeine. A more favourable hypothesis seems to be that caffeine stimulates the CNS. Caffeine acts antagonistically on adenosine receptors, thereby inhibiting the negative effects adenosine induces on neurotransmission, arousal and pain perception. The hypoalgesic effects of caffeine have resulted in dampened pain perception and blunted perceived exertion during exercise. This could potentially have favourable effects on negating decreased firing rates of motor units and possibly produce a more sustainable and forceful muscle contraction. The exact mechanisms behind caffeine's action remain to be elucidated. [ABSTRACT FROM AUTHOR]

Ballistic protective helmets can impair heat dissipation. A cooling device in the helmet (cooling pad, CP) could help prevent heat problems in military personnel and potentially enhance comfort. This study examined the effects of CP on rectal and skin temperatures, heart rate, percent change in plasma volume, urine specific gravity, rating of perceived exertion, and other subjective measures while performing light work in a hot environment. It was hypothesized that the CP would act as an insulator to the head, which would not positively affect any physiological variable but could positively affect wearer subjective comfort or temperature. Participants performed a work protocol for approximately 2 hr. A ballistic vest, slacks, short-sleeved button-up shirt, and a ballistic helmet (one trial with CP and one trial without) were worn. Repeated measures analysis of variance (ANOVA) showed no differences (p > 0.05) between wearing and not wearing the CP for any physiological parameter. However, participants perceived the CP as cooler (p = 0.002). Other trends in perceptual data such as thermal strain and helmet comfort indicated the CP felt cooler. However, based on forehead temperature and participant comments, the CP lost its cooling ability relatively quickly (within approximately 30 min). [ABSTRACT FROM AUTHOR]

The Looking at Infant Feeding Today (LIFT) study examined the factors underlying the infant feeding choices of first-time mothers in the Leeds and Bradford areas of England experiencing material hardship, with a view to informing interventions aimed at increasing breastfeeding uptake amongst this group. This short report describes the novel methodology used to obtain data from a sample of pregnant women who are traditionally 'hard-to-reach' in deprived areas. This involved the use of trusted individuals such as midwives and multilingual health workers. A total of 449 women were approached; 441 (91.5%) agreed to participate and 303 returned completed questionnaires. Whilst 285 participants self-completed, 18 opted for interviewer assistance provided by a trained multilingual health worker. Feeding method up to 10 days after birth was obtained from the hospital records of 248 women (82.4% of eligible returns), and self-reported feeding method at six weeks was obtained from 273 women (90.7% of eligible returns). The study succeeded in obtaining data from a relatively deprived and hard-to-reach sample, with adequate numbers of participants in the subgroups of interest (teenage, left full time education age 16 or younger, household receiving income support or job seekers allowance, Asian or African-Caribbean). [ABSTRACT FROM AUTHOR]

The aim of this study is to explore reasons for and against prenatal testing and termination for a range of conditions in women from two different ethnic backgrounds. A total of 19 Pakistani and European women in West Yorkshire, UK, who either had a child with a genetic condition or had terminated a pregnancy for one, completed a questionnaire about their attitudes regarding prenatal testing and termination for 30 different fetal conditions and were interviewed about their reasons for their responses. There were more similarities than differences between the Pakistani and European white women. The most important factor in most women's decisions about termination of pregnancy was their perception of the quality of the life of a child with the genetic condition, in particular, whether the child would be 'suffering.' This was described as either physical suffering, as a result of medical treatment, or as emotional suffering, as a result of psychological and/or social factors. These findings highlight the need for detailed information about the potential quality of life for the child and the child's family to enable parents to make informed choices, particularly the extent to which the child is likely to suffer, the nature of such potential 'suffering' and the extent to which the child could lead a 'normal' life. The findings also challenge stereotypes about cultural differences in attitudes about termination of pregnancy. [ABSTRACT FROM AUTHOR]

A brief review is provided on the relationship of strength to muscle cross-sectional area (CSA). It is commonly believed that maximal force and CSA are strongly related. Studies examining varying levels of training status display discordant data suggesting complex relationships between training status, CSA and peak force. It has been reported that trained participants had a significantly larger force to CSA ratio (F/CSA) than untrained males and females. Therefore, it is difficult to attribute all force changes due to training to CSA changes. In general, studies of CSA and strength suggest that sex differences may exist. For example, recreationally trained female weightlifters produced higher F/CSA than males at lower velocities of contraction. Definitive conclusions regarding sex differences, force production and CSA are difficult because of limited studies and equivocal results among these studies. Some studies have also examined the impact of aging on F/CSA. These studies seem to follow the same pattern as studies on sex differences and training status, with data suggesting that F/CSA varies unpredictably across ages and that differences may be attributed to factors other than age alone. In the papers reviewed, the relationship between force and CSA is neither consistent nor simple. Although some of the discrepancies between studies could be attributed to methodological variations, this does not seem likely to explain all differences. The F/CSA relationship seems complex, and future studies are required to elucidate the relationships among key factors in the expression of strength. [ABSTRACT FROM AUTHOR]

This study compared independent effects of caffeine and aspirin on muscular endurance (repetitions), heart rate (HR), perceived exertion (RPE), and perceived pain index (PPI) during light resistance training bouts performed to volitional failure. It was hypothesized that the hypoalgesic properties of these ergogenic aids would decrease pain perception and potentially result in enhanced performance. College-aged men (n = 15) participated in a within-subjects, double-blind study with three independent, counterbalanced sessions wherein aspirin (10 mg x kg(-1)), caffeine (6 mg x kg(-1)), or matched placebo were ingested 1 hour before exercise, and RPE, HR, PPI, and repetitions (per set and total per exercise) were recorded at 100% of individual, predetermined, 12-repetition maximum for leg extensions (LE) and seated arm curls (AC). Repeated-measures analyses of variance were used for between-trial comparisons. Caffeine resulted in significantly greater (p < 0.05) HR (LE and AC), total repetitions (LE), and repetitions in set 1 (LE and AC) compared with aspirin and placebo. Aspirin resulted in significantly higher PPI in set 1 (LE). In LE, 47% of participants' performance exceeded the predetermined effect size (>or= 5 repetitions) for total repetitions, with 53% exceeding the effect size (>or= 2 repetitions) for repetitions in set 1 with caffeine (vs. placebo). In AC, 53% (total repetitions) and 47% (set 1 repetitions) of participants exceeded effect sizes with caffeine (vs. placebo), with only 13% experiencing decrements in performance (total repetitions). Aspirin also produced a higher PPI and RPE overall and in set 1 (vs. placebo). This study demonstrates that caffeine significantly enhanced resistance training performance in LE and AC, whereas aspirin did not. Athletes may improve their resistance training performance by acute ingestion of caffeine. As with most ergogenic aids, our analyses indicate that individual responses vary greatly. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study evaluated an existing SNOMED-CT((R)) model for structured recording of heart murmur findings and compared it to a concept-dependent attributes model using content from SNOMED-CT. METHODS: The authors developed a model for recording heart murmur findings as an alternative to SNOMED-CT's use of Interprets and Has interpretation. A micro-nomenclature was then created to support each model using subset and extension mechanisms described for SNOMED-CT. Each micro-nomenclature included a partonomy of cardiac cycle timing values. A mechanism for handling ranges of values was also devised. One hundred clinical heart murmurs were recorded using purpose-built recording software based on both models. RESULTS: Each micro-nomenclature was extended through the addition of the same list of concepts. SNOMED role grouping was required in both models. All 100 clinical murmurs were described using each model. The only major differences between the two models were the number of relationship rows required for storage and the hierarchical assignments of concepts within the micro-nomenclatures. CONCLUSION: The authors were able to capture 100 clinical heart murmurs with both models. Requirements for implementing the two models were virtually identical. In fact, data stored using these models could be easily interconverted. There is no apparent penalty for implementing either approach. [ABSTRACT FROM AUTHOR]

This study surveyed the views of 78 women who had a sibling with Down's syndrome towards using prenatal diagnosis and termination. Other data were collected, including participants' perceptions of the difficulty of caring for a child with Down's syndrome, perceived familial approval of selective termination, and the quality of the sibling relationship. Fifty-four per cent of respondents said they would use diagnostic tests for Down's syndrome in a future pregnancy, 37% would not, and 9% were unsure. In contrast, 33% would consider terminating a pregnancy for Down's syndrome, 53% would not consider termination, and 14% were unsure. Logistic regression showed that the perceived difficulty of caring for a child with Down's syndrome and perceived parental approval of selective termination were the strongest overall predictors of both attitudes. However, women who were younger than their affected sibling were more likely to want to use prenatal diagnosis, and a generally favourable attitude towards abortion predicted a favourable view towards terminating a pregnancy for Down's syndrome. In general, a positive picture emerged of having a sibling with Down's syndrome although around one-third of the women viewed the impact on themselves and their family as negative and this was reflected in their attitudes towards prenatal testing and termination. [ABSTRACT FROM AUTHOR]

BACKGROUND: Many studies have revealed that a sense of control is a major contributing factor to a woman's birth experience and her subsequent well-being. Since not all studies conceptualize 'control' in the same way or distinguish between 'external' and 'internal' control, the purpose of this study is to advance understanding of how these senses of control relate to each other. METHODS: Questionnaires were sent to women 1 month before birth to assess their preferences and expectations and at 6 weeks after birth to discover their experiences and assess psychological outcomes. Data are presented from 1146 women. Three control outcomes were considered: feeling in control of what staff do to you, feeling in control of your own behavior, and feeling in control during contractions. RESULTS: Women were less likely to report being in control of staff (39.5%) than in control of their own behavior (61.0%). Approximately one-fifth of the sample felt in control in all three ways, and another one-fifth did not feel in control in any of them. Parity was strongly associated with feeling in control, with multiparas feeling more in control than primiparas in all cases. In logistic regression analyses, feeling in control of staff was found to relate primarily to being able to get comfortable, feeling treated with respect and as an individual, and perceiving staff as considerate. Feeling in control of one's behavior and during contractions were primarily related to aspects of pain and pain relief, but also to antenatal expectations of control. Worry about labor pain was also an important antenatal predictor for primiparas. All three control outcomes contributed independently to satisfaction, with control of staff being the most significant; relationships with emotional well-being were also demonstrated. CONCLUSIONS: All three types of control were important to women and contributed to psychological outcomes. Internal and external control were predicted by different groups of variables. Caregivers have the potential to make a significant difference to a woman's experience of childbirth. The ways in which women are helped to deal with pain will affect internal control; the extent to which they feel that they are actually cared about, rather than care being something that is done to them, will affect external control. Both contribute to satisfaction and emotional well-being. [ABSTRACT FROM AUTHOR]

OBJECTIVES: There is little information on the probability of assertive behaviour, interpersonal anxiety and self-efficacy in the literature regarding dietitians. The objective of this study was to establish baseline information of these attributes and the factors affecting them. METHOD: Questionnaires collecting biographical information and self-assessment psychometric scales measuring levels of probability of assertiveness, interpersonal anxiety and self-efficacy were mailed to 350 subjects, who comprised a random sample of dietitians registered with the Health Professions Council of South Africa. RESULTS: Forty-one per cent (n=145) of the sample responded. Self-assessment inventory results were compared to test levels of probability of assertive behaviour, interpersonal anxiety and self-efficacy. The inventory results were compared with the biographical findings to establish statistical relationships between the variables. The hypotheses were formulated before data collection. CONCLUSION: Dietitians had acceptable levels of probability of assertive behaviour and interpersonal anxiety. The probability of assertive behaviour was significantly lower than the level noted in the literature and was negatively related to interpersonal anxiety and positively related to self-efficacy. [ABSTRACT FROM AUTHOR]