What is the diagnostic yield of a standardized sequential clinical evaluation of patients presenting to an emergency department with syncope?
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Adolescent↗
Biomedical subjects
J O'Connor
Publications and source records attributed to J O'Connor.
Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis.
Soluble products of activated immune cells include reactive oxygen species (ROS) and nitric oxide (NO) with a high potential to induce biochemical modifications and degenerative changes in areas of inflammation in the central nervous system (CNS). Previously, we demonstrated an increased production of ROS by activated mononuclear cells (MNC) of patients with multiple sclerosis (MS) compared to those of controls, and development of oxidative damage to total DNA in association with inflammation in chronic active plaques. The current study aimed to determine whether mitochondrial (mt)DNA is affected by oxidative damage, and whether oxidative damage to mitochondrial macromolecules (including mtDNA) is associated with a decline in the activity of mitochondrial enzyme complexes. Using molecular and biochemical methods we demonstrate a trend for impaired NADH dehydrogenase (DH) activity and a possible compensatory increase in complex IV activity in association with oxidative damage to mtDNA in chronic active plaques. Immunohistochemistry confirms the increase of oxidative damage to DNA predominantly located in the cytoplasmic compartment of cells in chronic active plaques. These observations suggest that oxidative damage to macromolecules develops in association with inflammation in the CNS, and may contribute to a decline of energy metabolism in affected cells. As observed in neurodegenerative diseases of non-inflammatory origin, decreased ATP synthesis can ultimately lead to cell death or degeneration. Therefore, elucidation of this pathway in MS deserves further studies which may identify neuroprotective strategies to prevent tissue degeneration and the associated clinical disability.
Adolescent↗
Adrenergic stimulation regulates Na(+)/Ca(2+)Exchanger expression in rat cardiac myocytes.
The Na/Ca exchanger protein encoded by the NCX1 gene provides the predominant mechanism for calcium efflux during cardiac relaxation. Because beta -adrenergic stimulation increases expression of Ca(2+)channels (Ca(2+)influx) in cardiac myocytes, we tested the hypothesis that isoproterenol would concomitantly augment expression of NCX1. Four hour treatment of neonatal myocytes with isoproterenol significantly increased NCX1 gene and protein expression, and increased the rate of transcript initiation. Alpha-adrenergic stimulation significantly decreases NCX1 mRNA levels. Calcium transient measurements revealed that for cells that had been pretreated with isoproterenol there was a faster relaxation rate of the Ca(2+)transient in the presence of thapsigargin, indicating an enhanced rate of intracellular Ca(2+)removal. We conclude that effectors that increase calcium channel expression in neonatal myocytes also augments NCX1 gene and protein expression over a similar time course, and that this is due to enhanced NCX1 transcription. The regulation of expression of NCX1 by adrenergic pathways may play an important role in regulation of excitation-contraction coupling in cardiac myocytes.
Adrenergic alpha-Agonists↗
Relationships between the fatty acid composition of muscle and erythrocyte membrane phospholipid in young children and the effect of type of infant feeding.
Muscle membrane fatty acid (FA) composition is linked to insulin action. The aims of this study were to compare the FA composition of muscle and erythrocyte membrane phospholipid in young children; to investigate the effect of diet on these lipid compositions; and to investigate differential incorporation of FA into muscle, erythrocyte and adipose tissue membrane phospholipid, and adipose tissue triglyceride. Skeletal muscle biopsies and fasting blood samples were taken from 61 normally nourished children (45 males and 16 females), less than 2 yr old (means +/- SE, 0.80 +/- 0.06 yr), undergoing elective surgery. Adipose tissue samples were taken from 15 children. There were significant positive correlations between muscle and erythrocyte docosahexaenoic acid (DHA) (r = 0.44, P < 0.0001), total n-3 polyunsaturated fatty acids (PUFA) (r = 0.39, P = 0.002), and the n-6/n-3 PUFA ratio (r = 0.39, P = 0.002). Adipose tissue triglyceride had lower levels of long-chain PUFA, especially DHA, than muscle and erythrocytes (0.46 +/- 0.18% vs. 2.44 +/- 0.26% and 3.17 +/- 0.27%). Breast-fed infants had higher levels of DHA than an age-matched group of formula-fed infants in both muscle (3.91 +/- 0.21% vs. 1.94 +/- 0.18%) and erythrocytes (3.81 +/- 0.40% vs. 2.65 +/- 0.23%). The results of this study show that (i) erythrocyte FA composition is a reasonable index of muscle DHA, total n-3 PUFA, and the n-6/n-3 PUFA ratio; (ii) breast feeding has a potent effect on the FA composition of all these tissues; and (iii) there is a wide range in long-chain PUFA levels in muscle, erythrocytes, and adipose tissue.
Adipose Tissue↗
The Roper, Logan and Tierney (1996) model: perceptions and operationalization of the model in psychiatric nursing within a health board in Ireland.
This study aimed to determine whether the Roper, Logan & Tierney model was an appropriate model for planning nursing care for clients who are mentally ill. Data were collected from two sources in one Health Board region in Ireland. A care plan audit was used to evaluate the extent to which the Roper, Logan & Tierney model was used to assess, plan and evaluate nursing care in nursing documentation. Qualitative interviews with nurses explored their experiences of using the model and their perceptions of the model's usefulness and appropriateness for planning care. Both data sets were complementary, the qualitative data often providing contextual information which helped put the findings into perspective. It was found that there was little evidence that the Roper, Logan and Tierney model guided care planning and that goals and nursing interventions were frequently not explicitly documented. Interviews with nurses indicated that they lacked educational preparation for using the model and found the model constraining and physically orientated. The appropriateness of the Roper, Logan and Tierney model for planning care for clients who are mentally ill is questioned. It is suggested that nurses need to be adequately prepared if they are to use a model appropriately. Consideration should be given when selecting a model as to its 'fit' with the needs of the client group and the ward team philosophy.
Attitude of Health Personnel↗
Child abuse and the clinical course of drug misuse.
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Adolescent↗
Androgen deprivation and four courses of fixed-schedule suramin treatment in patients with newly diagnosed metastatic prostate cancer: A Southwest Oncology Group Study.
PURPOSE: To assess the feasibility of administering a combination of suramin and hydrocortisone in addition to androgen deprivation in a cooperative group setting; to assess the feasibility of treatment with multiple courses of suramin; and to assess progression-free and overall survival in patients with newly diagnosed metastatic prostate cancer who underwent such treatment. PATIENTS AND METHODS: Patients with newly diagnosed metastatic prostate cancer who had adequate hematologic, hepatic, renal, neurologic, and coagulation parameters were treated by combined androgen deprivation and suramin plus hydrocortisone. Suramin was administered on a 78-day fixed dosing schedule (one cycle), and suramin treatment cycles were repeated every 6 months for a total of four cycles. The statistical design was developed on the basis of the feasibility of administering suramin, as judged by the number of patients who developed neurotoxicity of grade 3 or higher or by treatment interruption of 4 weeks or longer due to any persistent suramin-related toxicity. RESULTS: Of the 62 patients enrolled onto the study between August 1994 and January 1997, 59 were eligible and assessable for toxicity on the first cycle. Thirty-two (54%) of 59 patients received a second cycle, 13 (22%) of 59 patients received a third cycle, and only five patients (8%) received a fourth cycle. During the first cycle, 27 patients were removed from the study: 17 because of toxicity, five because of disease progression, two who had died, and three because of other reasons. There was one therapy-related death. Grade 4 toxicities were noted in 11 and three patients during first and second courses, respectively. Neurotoxicity of grade 3 or higher was observed in nine and seven patients during the first and second cycles, respectively. Fifteen patients had treatment interruptions of 4 weeks or longer. Overall, only 54% (95% confidence interval, 41% to 67%) of the patients demonstrated acceptable limits of toxicity. CONCLUSION: Suramin plus hydrocortisone and androgen deprivation has limited applicability in the treatment of patients with newly diagnosed metastatic prostate cancer.
Adult↗
Treatment of trauma-associated hypothermia in children: evidence-based practice.
BACKGROUND: Hypothermia is a serious immediate consequence of traumatic injury in children. Although numerous studies have addressed the treatment of hypothermia in adults after trauma or surgery, few have examined this issue in injured children. OBJECTIVES: To evaluate the research literature on when and how to treat hypothermia during emergency care of children with trauma and to apply these findings to clinical nursing practice. METHODS: Electronic literature searches conducted periodically for 3 years yielded more than 50 publications on hypothermia and its treatment in trauma and surgical patients. Publications were grouped by cause of hypothermia and by warming methods. Single case reports and publications related to submersion injuries were excluded. RESULTS: Three clinical trials of patients with head injuries included adolescents aged 15 years and older. One study compared peripheral and core warming methods used during operative management of infants and young children. Only one study evaluated core warming in children with trauma. DISCUSSION: The treatments examined in the few research-based studies on the treatment of hypothermia during emergency care of children with trauma were given low recommendations. Although the warming methods were successful in selected surgical and adult patients, the methods cannot be recommended for treating children with trauma because of the lack of evidence-based findings. CONCLUSIONS: Caution should be used when extrapolating published data on the treatment of hypothermia in injured adults to injured children. Ongoing clinical trials should evaluate in children with trauma those warming methods that have been used successfully in surgical patients.
Adolescent↗
The bromodeoxyuridine comet assay: detection of maturation of recently replicated DNA in individual cells.
The single-cell gel electrophoresis (Comet) assay is a relatively simple method of measuring DNA single strand breaks and alkali-labile sites in individual cells. We have combined this with bromodeoxyuridine (BrdUrd) labeling of DNA and immunolocalization of the BrdUrd to assess DNA replicative integrity on a single-cell basis. We show that the existence of strand discontinuities in recently replicated domains of DNA, caused during semiconservative replication or exacerbated by the arrest of replicative polymerases at UV irradiation- or chemical-induced lesions, can be detected in individual cells. Data obtained from BrdUrd-Comets are consistent with biochemical data derived with a range of techniques showing that DNA replication involves the creation of strand breaks or gaps adjacent to recently replicated material, and that DNA damage prolongs the duration of such discontinuities where DNA polymerases are stalled opposite lesions (R. T. Johnson et al, The Legacy of Cell Fusion, pp. 50-67, Oxford: Science Publications, 1994; R. B. Painter, J. Mol. Biol., 143: 289-301, 1980.). Compared with standard biochemical techniques, the BrdUrd-Comet assay is simple and suitable for the accurate and automatable assessment of replicative integrity in very small numbers of mammalian cells, such as may be obtained by biopsy.
Animals↗
Golgi structure correlates with transitional endoplasmic reticulum organization in Pichia pastoris and Saccharomyces cerevisiae.
Golgi stacks are often located near sites of "transitional ER" (tER), where COPII transport vesicles are produced. This juxtaposition may indicate that Golgi cisternae form at tER sites. To explore this idea, we examined two budding yeasts: Pichia pastoris, which has coherent Golgi stacks, and Saccharomyces cerevisiae, which has a dispersed Golgi. tER structures in the two yeasts were visualized using fusions between green fluorescent protein and COPII coat proteins. We also determined the localization of Sec12p, an ER membrane protein that initiates the COPII vesicle assembly pathway. In P. pastoris, Golgi stacks are adjacent to discrete tER sites that contain COPII coat proteins as well as Sec12p. This arrangement of the tER-Golgi system is independent of microtubules. In S. cerevisiae, COPII vesicles appear to be present throughout the cytoplasm and Sec12p is distributed throughout the ER, indicating that COPII vesicles bud from the entire ER network. We propose that P. pastoris has discrete tER sites and therefore generates coherent Golgi stacks, whereas S. cerevisiae has a delocalized tER and therefore generates a dispersed Golgi. These findings open the way for a molecular genetic analysis of tER sites.
Carrier Proteins↗
Temperature measurement in pediatric trauma patients: A comparison of thermometry and measurement routes.
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Adolescent↗
Simple CPR: A randomized, controlled trial of video self-instructional cardiopulmonary resuscitation training in an African American church congregation.
STUDY OBJECTIVE: Despite the proven efficacy of cardiopulmonary resuscitation (CPR), only a small fraction of the population knows how to perform it. As a result, rates of bystander CPR and rates of survival from cardiac arrest are low. Bystander CPR is particularly uncommon in the African American community. Successful development of a simplified approach to CPR training could boost rates of bystander CPR and save lives. We conducted the following randomized, controlled study to determine whether video self-instruction (VSI) in CPR results in comparable or better performance than traditional CPR training. METHODS: This randomized, controlled trial was conducted among congregational volunteers in an African American church in Atlanta, GA. Subjects were randomly assigned to receive either 34 minutes of VSI or the 4-hour American Heart Association "Heartsaver" CPR course. Two months after training, blinded observers used explicit criteria to assess CPR performance in a simulated cardiac arrest setting. A recording manikin was used to measure ventilation and chest compression characteristics. Participants also completed a written test of CPR-related knowledge and attitudes. RESULTS: VSI trainees displayed a comparable level of performance to that achieved by traditional trainees. Observers scored 40% of VSI trainees competent or better in performing CPR, compared with only 16% of traditional trainees (absolute difference 24%, 95% confidence interval 8% to 40%). Data from the recording manikin confirmed these observations. VSI trainees and traditional trainees achieved comparable scores on tests of CPR-related knowledge and attitudes. CONCLUSION: Thirty-four minutes of VSI can produce CPR of comparable quality to that achieved by traditional training methods. VSI provides a simple, quick, consistent, and inexpensive alternative to traditional CPR instruction, and may be used to extend CPR training to historically underserved populations.
Adult↗
Characteristics of effective village treatment assistants: the Kongwa Trachoma Project.
PURPOSE: Mass treatment of entire communities with tetracycline eye ointment is one method for treatment of hyperendemic trachoma. Village Treatment Assistants (VTAs) are often recruited to implement mass treatment in their neighborhoods. We determined characteristics of these volunteers that were associated with effective treatment outcomes. METHODS: Three villages received mass treatment with tetracycline ointment daily for four weeks as part of a clinical trial. Community members selected VTAs to administer the ointment. Trachoma status was assessed by grading photographs of the tarsal conjunctiva in a sample of children randomly selected from households in each village. Change in trachoma status was determined from baseline to one month post treatment. VTA performance outcome was "good" if there was improvement in the majority of the children treated by the VTA, "poor" if the majority worsened, and "neutral" if there was neither improvement nor worsening on average. Trained interviewers administered a questionnaire measuring socioeconomic and demographic variables to 82% of all VTAs. RESULTS: A total of 280 VTAs (229 with questionnaire) were evaluated: 36.8% had good outcomes and 12.5% had poor outcomes. Those VTAs with poor outcomes tended to be unmarried females (OR = 11.73) and those who used a bicycle to carry out treatment activities (OR = 4.16). Formal education or prior experience as a health worker were not predictors of performance. CONCLUSION: Community selection and effective, non-formal, training are key components for the use of VTAs in mass treatment campaigns. Prior education or health training does not play a major role in effectiveness. The possible effects of gender roles in the community need to be considered in program design.
Anti-Bacterial Agents↗
Substance abuse in an Irish antenatal population.
Substance abuse is prevalent in Ireland. The potential sequelae for abuser and carer are many. In pregnancy there are further problems. We assessed the prevalence of substance abuse in our antenatal population using an anonymous questionnaire and urine toxicology screening. We examined 522 women and 18 (3.4%) had positive urine toxicology. The anonymous questionnaire failed to identify all of these women. No typical patient profile emerged when the demographic features were studied. We believe that our study has underestimated the true prevalence of substance abuse in our antenatal population and many factors may have contributed to this. Substance abuse in pregnancy remains a difficult problem to quantify and for the future the main focus of attention must be on education and prevention.
Journal Article↗
Differences in urinary excretion patterns of the hLH beta core fragment in premenopausal, perimenopausal, and postmenopausal women.
OBJECTIVE: The heterodimeric luteinizing hormone beta core fragment (hLH beta cf) is a highly stable urinary analyte reflective of circulating hLH. It is measured easily because of its high molar content and has none of the multiple isoforms and subunit dissociation problems of LH urinary measurements. As part of a long-term effort to develop new biochemical assays to stage women during the perimenopausal transition, we have examined the patterns of urinary excretion of this metabolite of hLH in premenopausal, perimenopausal, and postmenopausal women. DESIGN: We measured the concentration of the hLH beta cf in 10 consecutive first morning void urine specimens from premenopausal, perimenopausal, and postmenopausal women. Day 1 of collection was the first day of menses in the cycling women. RESULTS: Postmenopausal women exhibited a widely fluctuating pattern of LH beta core fragment excretion, which is not correlated with hLH measured by immunofluorometric assay or with follicle-stimulating hormone measured by immunofluorometric assay. The postmenopausal group was easily distinguished from premenopausal women on the basis of an area-under-the-curve concentration function. Perimenopausal women displayed intermediate hLH beta cf concentrations; some clearly were in postmenopausal ranges, and others were in the premenopausal ranges. CONCLUSIONS: The pattern of excretion and concentrations of the hLH beta cf is significantly different between premenopausal and postmenopausal women. Perimenopausal women exhibited intermediate changes. The capability to measure this type of stable urinary metabolite as a reflection of changes in dynamics of its parent circulating hormone offers new possibilities in the development and application of large-scale testing that does not require blood sampling.
Adult↗
Large scale screening of the mitochondrial DNA reveals no pathogenic mutations but a haplotype associated with multiple sclerosis in Caucasians.
We report the first large-scale screening of mitochondrial (mt) DNA in 77 Caucasian patients with relapsing-remitting or secondary progressive form of multiple sclerosis (MS) and in 84 Caucasian controls by using the method of restriction site polymorphism and haplotype analysis. No pathogenic mtDNA mutation was found in association with MS. However, mtDNA haplotypes K* and J* defined by the simultaneous presence of Ddel restriction sites at nucleotides 10,394 and 14,798 of the mtDNA in haplogroups K and J showed association with MS at a P-value of 0.001. A relative increase of MS patients compared to controls either with the J* or with the K* haplotype (+10,394Ddel/+14,798Ddel in haplogroup J or K) also was detected (each with a P<0.05). No distinct phenotypic characteristics of MS were observed when clinical data of patients with haplotypes K* or J* were analyzed. In addition to previous complete sequencing in several MS patients, the population screening of mtDNA presented here suggests that mtDNA point mutations are not likely to be involved in the pathogenesis of typical forms of MS. However, the mitochondrial genetic background (haplotype K* and J*) may moderately contribute to MS susceptibility. The reported association between MS and Leber's hereditary optic nerve atrophy, a disease caused by mtDNA point mutations preferentially occurring in haplogroup J, may be at least in part related to the overlapping mitochondrial genetic background of the two diseases.
Adult↗
Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer.
PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.
Aged↗
Does arthritis progress in the retained compartments after 'Oxford' medial unicompartmental arthroplasty? A clinical and radiological study with a minimum ten-year follow-up.
We determined the outcome of 56 'Oxford' unicompartmental replacements performed for anteromedial osteoarthritis of the knee between 1982 and 1987. Of these, 24 were in patients who had died without revision, one was lost to follow-up and two had been revised. Of the remaining 29 knees, 26 were examined clinically and radiologically, two were only examined clinically and one patient was contacted by telephone. The mean age of the patients was 80.3 years. At a mean follow-up of 11.4 years (10 to 14) the measurements of the knee score, range of movement and degree of deformity were not significantly different from those made one to two years after operation, except that the range of flexion had improved. Comparison of fluoroscopically-controlled radiographs at a similar interval of time showed no change in the appearance of the lateral compartments. The retained articular cartilage continued to function for ten or more years which suggests that anteromedial osteoarthritis may be considered as a focal disorder of the knee. This justifies continued efforts to develop methods of treatment which preserve intact joint structures.
Aged↗