Search

This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population. Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL. Breath alcohol concentration was measured using the AlcoSense ™ Breathalyser on three separate visits. The primary end-point was the number of patients who were above the legal threshold for drink driving in Ireland. In total, 50 patients were recruited. 36 (68%) were female. The most common diagnosis was breast cancer (56%). Ten (20%) patients had metastatic disease and 4 (8%) had liver metastases. The mean paclitaxel dose administered was 118 mg. The mean amount of ethanol infused was 7.7 g. 27 patients had a detectable breath alcohol level on at least one visit. The mean breath alcohol concentration was 2 mcg/100 mL or 0.02 mg/L of breath. The maximum concentration of ethanol in exhaled breath was 11 mcg/100 mL or 0.11 mg/L which is 50% of the statutory limit for drink driving in Ireland. A weak correlation was observed between ethanol concentration in exhaled breath and the total amount of ethanol administered. Although no patient exceeded the general limit for drink driving in Ireland, three (6%) participants had a breath alcohol concentration above the threshold for professional, learner or novice drivers. Although definitive conclusions are limited by relatively small numbers, it seems unlikely that weekly paclitaxel infusions pose any significant risk to patients driving.

Purpose The purpose of this study was to evaluate whether persons who stutter (PWS) reported benefits related to their stuttering and to describe the nature of those benefits. Method A mixed-methods approach was utilized. Qualitative content analysis was conducted with 5 different books, which included chapters written by PWS that focused on the experiences of stuttering and psychosocial aspects of the condition. In addition, 4 survey items measuring perceived benefits from stuttering were administered to 322 adults who stutter. Results Three major themes with 11 subthemes were identified in the qualitative analysis. PWS reported personal benefits from stuttering, including positive behavioral outcomes, cultivation of determination, feeling stronger, and emotional growth. Relationship benefits included social support access, deepening of relationships, and increased sensitivity to others. Changes in perspective included gained perspective about stuttering, gained perspective on life, a sense of appreciation, and finding positive meaning in challenges. Quantitative analysis revealed that over 90% of PWS agreed that stuttering has made them more understanding of other people, and over 80% agreed that it has made them stronger. Conclusion It is concluded that benefit finding among PWS should continue to be investigated in order to obtain a more complete understanding of the psychosocial aspects of stuttering and potentially to enhance therapeutic and support services for PWS.

Purpose This study investigated the disclosure practices of people who stutter, and the relationship between disclosure of stuttering and quality of life. Method Participants were 322 adults who stutter recruited from speech-language pathologists and support group leaders. Participants completed a survey that contained items measuring level of disclosure of stuttering, as well as a global measure of self-rated quality of life. Participants were grouped into low, average, and high quality of life subgroups. Analysis of variance tests compared disclosure levels among these subgroups. Results The low quality of life subgroup reported significantly lower levels of disclosure compared to both the average and high quality of life subgroups. Participants with self-help/support group experience for stuttering demonstrated significantly higher levels of disclosure of stuttering compared to individuals without such experience. In addition, a substantial number of participants in the overall sample reported that they more than rarely feel the need to conceal stuttering from others (40%), and that no one knows that they stutter in many areas of life (37%). Conclusions Attempts to conceal stuttering in at least some life situations are not uncommon among adults who stutter. However, being involved in self-help support groups may be a helpful way of increasing disclosure of stuttering. Speech-language pathologists should become aware of the positive relationship between disclosure of stuttering and quality of life and its relevance in assessment and treatment when working with people who stutter.

Purpose This study aimed to identify contributors to communicative participation in adults who stutter. Specifically, it was of interest to determine whether psychosocial variables of self-esteem, self-efficacy, and social support were predictive of communicative participation beyond contributions of demographic and speech-related variables. Method Adults who stutter ( N = 339) completed an online survey that included measures of communicative participation, self-esteem, self-efficacy, social support, self-reported speech-related variables (speech usage, number of years stuttering, history of treatment and self-help support group participation for stuttering, and physical speech disruption severity), and demographics (age, sex, living situation, education, and employment status). Hierarchical regression was performed for prediction of communicative participation, in addition to calculating Spearman correlations between social roles variables, communicative participation, and physical speech disruption severity. Results After controlling for demographic and speech-related variables, self-esteem, self-efficacy, and social support each significantly predicted communicative participation in adults who stutter. Large correlations were observed between communicative participation and measures of social roles, whereas medium correlations were observed between physical speech disruption severity and measures of social roles. Conclusions Communicative participation in adults who stutter is associated with a variety of demographic, speech-related, and psychosocial variables. Speech-language pathologists should be aware of predictors of communicative participation such as self-esteem, self-efficacy, and social support, in addition to severity of physical speech disruptions. They should consider and evaluate these factors in clients who stutter and target them in treatment if necessary.

Acetaminophen (also known as paracetamol) is a commonly used over-the-counter pain medication, but recent evidence suggests that a single exposure or prenatal exposure may have significant behavioral effects. This investigation aimed to determine whether acetaminophen could disrupt memory formation in an object-recognition task and to quantify potential changes in memory-related signaling cascades in the hippocampus of mice after acetaminophen administration. Using male mice, we examined the effect of a single subcutaneous injection of acetaminophen on the object-recognition task, a single-trial, hippocampus-dependent memory task. We also investigated potential changes in the activation of extracellular signal-regulated kinase (ERK) in the dorsal mouse hippocampus 1 hr after a subcutaneous injection of acetaminophen. We found that 50 mg/kg and 100 mg/kg interfered with performance in the object-recognition memory task, whereas 10 mg/kg did not. We also found that a single 50 mg/kg injection of acetaminophen significantly increased p42 ERK phosphorylation in the dorsal mouse hippocampus. Overall, these results suggest that a single dose of acetaminophen can have significant effects on memory and alters signaling kinases critical for memory consolidation. Further work is needed to determine the involved mechanisms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

BACKGROUND For Estrogen Receptor (ER) positive, early stage breast cancer, the 21 gene Recurrence Score (RS) has clinical use both as a prognostic tool and to predict chemotherapy benefit. The availability of this tool in Ireland has led to a reduction in the use of adjuvant chemotherapy for women with lymph node (LN) negative disease. However, the RS is not routinely funded for patients with LN positive (LN+) breast cancer in Ireland. In addition, there are limited international data on the use of this tool in the preoperative setting. In this prospective observational study, we are investigating whether access to the 21 gene RS leads to a reduction in the receipt of chemotherapy for patients with ER+, LN+ breast cancer, and to correlate the 21 gene RS with response to preoperative systemic therapy. TRIAL DESIGN This is a national, multi-site, prospective, observational study that will examine the impact of the 21 gene RS on chemotherapy recommendations in both the neoadjuvant and adjuvant setting. Prior to and following tumor testing with the 21 gene RS, Physicians will complete a questionnaire which details type and strength of systemic therapy recommendations. ELIGIBILITY Cohort 1 (postoperative) will include patients with ER+ tumors of any size with involvement of 1-3 lymph nodes (N1 including micrometastases). Cohort 2 (preoperative) will include patients with ER+, T2-T4 tumors with biopsy proven nodal metastases. Both cohorts will have ECOG PS 0 or 1 and be fit for consideration of chemotherapy as determined by the Investigator. SPECIFIC AIMS The primary endpoint is the percentage reduction in the number of patients for whom treating physicians recommend chemotherapy after testing with 21 gene RS. Secondary endpoints include the correlation between the 21 gene RS and residual cancer burden score, as well as pathological, clinical and radiological response rates. The economic impact of the 21 gene RS in ER+, LN+ will also be assessed. STATISTICAL METHODS The sample size is based on similar decision impact studies conducted in other countries. Physician recommendations for chemotherapy pre 21-gene RS and recommendations post 21-gene RS testing will be compared and percentage change estimated with 95% confidence intervals. For secondary endpoints, the Pearson correlation coefficient (rho) will be used to examine the strength of the correlation between the 21 gene RS category and response. A budget impact model will be used to estimate the cost reduction in adjuvant chemotherapy as a result of 21-gene RS testing. PRESENT ACCRUAL AND TARGET ACCRUAL Target accrual is 75 in each of the neoadjuvant and adjuvant cohorts to total 150 patients. Supported by Genomic Health. Citation Format: Keegan NM, Milewski M, Kelly CM, Murphy V, Chao C, Walsh J, Kennedy MJ, O'Connor M, Murphy C, O'Reilly S, Keane M, Duffy K, Hennessy B, Morris PG. The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor (ER) positive, lymph node positive early stage breast cancer in Ireland [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-03.

DYT1 primary torsion dystonia is an autosomal dominant disorder caused by deletion of a GAG triplet in exon 5 of the DYT1 gene. A significant proportion of individuals with early-onset generalized dystonia is believed to be DYT1 mutation carriers. We assessed the frequency of the GAG deletion in the DYT1 gene in a group of 61 Polish probands with clinical diagnosis of primary dystonia. The deletion was identified in four probands presenting with early-onset generalized disease (7%). Further studies in probands' families revealed two symptomatic and nine asymptomatic mutation carriers. We tested all mutation-positive individuals for the presence of some common polymorphisms within the DYT1 gene. Two of the 15 mutation-positive individuals additionally carried polymorphisms in 3'-UTR of the gene. Early onset in a limb and progression toward a generalized form, but not family history of dystonia, are indicative of DYT1 dystonia in Polish dystonic individuals.

Objectives: This article discusses the toxicity of the most common poisonous plants known to cause life-threatening systemic effects or death in dogs and cats as reported to the ASPCA Animal Poison Control Center (APCC). Data sources: The article presents an overview of geographic distribution, toxic principle, clinical signs, clinical chemistry alterations, and treatment of intoxication as reported in the literature and based upon data retrieved from the APCC between January 2001 and December 2003. Summary: Most plant exposures in dogs or cats result in mild to moderate signs of vomiting and diarrhea while liver, kidney, central nervous system, or cardiovascular effects are rare. Some garden or household plants can cause serious systemic effects or death when a small amount of plant material has been ingested. Based on APCC records, the most frequently reported poisonous plants causing serious systemic effects include Lily (Lilium and Hemerocallis spp.), Azalea (Rhododendron spp.), Oleander (Nerium oleander), Sago palm (Cycas spp.), Castor bean (Ricinus communis), Kalanchoe (Kalanchoe spp.), and Autumn Crocus (Colchicum autumnale). Conclusion: Despite the variety of toxins present in the plants listed above, early clinical signs of toxicosis in dogs and cats can be nonspecific and can include vomiting, lethargy, anorexia, salivation, or diarrhea. Cardiac arrhythmias may be present with oleander, azalea, or kalanchoe ingestion. Evidence of liver or kidney damage (Cycas, Lilium, Hemerocallis spp., Ricinus communis) may occur 1–2 days after the exposure. Treatment consists of early decontamination and supportive care and may vary according to the type of plant involved and clinical signs present.

Zebra finches communicate via several distinct vocalizations, of which song is the most studied. Behavioral observations indicate that adults are able to discriminate among the songs of different conspecific individuals. In the wild, zebra finches live in structured but mobile colonies, and encounter new individuals on a frequent basis. Thus it seems plausible that adult finches might have the capacity to recognize and remember new songs they encounter on a single day, but this has never been directly tested. Here we devised a simple observational assay to determine whether adult male zebra finches show recognition of a song they have heard repeatedly from taped playbacks, over a single three hour period the day before. We quantified the rate of production of six discrete behaviors (short calls, contact calls, singing, short hops, long hops, and beak swipes) made by adult male zebra finches as they listened to the playbacks. At the onset of song playback, all birds suspended these behaviors and sat silently-occasionally moving their heads. Then, after a measurable period ("response latency"), the birds resumed these activities. We observed that the response latency was long (approximately 10 min) when birds were hearing a particular song for the first time. The response latency was much shorter (approximately 1-2 min) when the birds had heard the same song the day before. Thus, functional song memories must result from as little as 3 h of passive song-exposure. These results suggest that ongoing song learning may play a natural role in the daily life of adult zebra finches, and provide a behavioral reference point for studies of molecular and physiological plasticity in the adult auditory system.

We previously reported the isolation of a laboratory-derived Staphylococcus aureus mutant, 523k, that has constitutive low-level resistance to vancomycin (MIC = 5 micrograms/ml) and teicoplanin (MIC = 5 micrograms/ml) and elaborates a ca. 39-kDa cytoplasmic protein that was not detected in the parent strain 523 (MIC = 1 micrograms/ml). We have now detected the protein in strain 523 by immunoblotting with antiserum raised against the protein. Consistent with our initial observations, densitometric analysis of the immunoblots revealed an increased production of the protein in 523k compared with that of the susceptible parent 523. The 5' region of the gene encoding the protein of interest was identified by nucleotide sequencing a PCR product amplified from the genome of 523k with degenerate primers designed to encode the amino acid sequence of proteolytic peptides obtained from the protein. The remainder of the gene was identified by library screening, PCR, and nucleotide sequencing. The gene encodes a 36.7-kDa protein with homology to a family of bacterial NAD+-dependent, D-specific 2-hydroxyacid dehydrogenases which includes both D-lactate dehydrogenase and the enterococcal vancomycin resistance protein VanH and is therefore designated ddh. Increased production of the product of ddh, Ddh, was associated with increased D-lactate dehydrogenase activity in 523k, a finding which suggested that Ddh is likely to be the D-lactate dehydrogenase previously identified in S. aureus. The increased D-lactate dehydrogenase activity in strain 523k and the structural similarities among Ddh, D-lactate dehydrogenase, and VanH suggest that overproduction of Ddh might play a role in vancomycin resistance in this strain.

Background: The combination of the anthracycline, doxorubicin with cyclophosphamide (AC) is a widely used chemotherapy regimen in early stage breast cancer. Studies have shown that dose dense chemotherapy (incorporating AC) improved both disease-free survival and overall survival compared to once every 3 week treatment with daily subcutaneous G-CSF support. An important advance in the use of dose dense chemotherapy regimens was the development of pegylated forms of G-CSF, which offered the convenience of a single subcutaneous injection, rather than multiple daily injections. Lipegfilgrastim is a pegylated long-acting covalent conjugate of filgrastim (G-CSF). In a pivotal randomised phase III study in breast cancer lipegfilgrastim was shown to be non-inferior to pegfilgrastim. Although lipegfilgrastim is licensed in Europe and can facilitate every 2 week (dose dense) scheduling of chemotherapy there are a lack of prospective data about its efficacy in this setting. In this prospective, non-interventional, study we are investigating the incidence of treatment-related neutropaenia following four cycles of dose dense AC with lipegfilgrastim support. Methods: The primary end point of this prospective, single arm study is to determine the incidence of treatment-related neutropaenia, defined as an absolute neutrophil count (ANC) of 38°C and ANC Citation Format: Lyons T, Mallet V, Collins D, Malone E, Milewski M, Egan K, Hennessy B, Grogan L, Breathnach O, Morris P. An observational study of dose dense chemotherapy with lipegfilgrastim support in early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-03.

Summary We have determined IgG subclass concentrations in 100 patients with aspirin-induced asthma and 80 healthy controls. Patients on chronic corticotherapy (n= 64) had significantly lower total IgG levels than patients not receiving steroids (n= 36) or controls. Corticotherapy was not associated with changes in the subclass distributions. In patients, the most striking finding was elevation of IgG4. It was not related to corticotherapy or serum IgE levels. The rise in IgG4 was accompanied by a modest, though statistically significant, depression of IgG1. No changes of IgG2 and IgG3 concentrations were observed. Thus, aspirin-induced asthma is characterized by a distinct pattern of distributions of IgG subclasses. It is suggested that in aspirin-induced asthma elevation of IgG4 might result from chronic antigenic stimulation, of viral origin, and that determination of IgG subclass distribution might be of clinical interest.

Development of the mammalian pancreas has been studied extensively in mice. The stages from budding of the pancreatic anlaga through endocrine and exocrine cell differentiation and islet formation have been described in detail. Recently, the homeodomain transcription factor PDX-1 has been identified as an important factor in the proliferation and differentiation of the pancreatic buds to form a mature pancreas. To evaluate the possibility of using zebrafish as a model for the genetic analysis of pancreas development, we have cloned and characterized PDX-1 from this organism. The deduced sequence of zebrafish PDX-1 contains 246 amino acids and is 95% identical to mammalian PDX-1 in the homeodomain. We also cloned zebrafish preproinsulin complementary DNA as a marker for islet tissue. By in situ hybridization we demonstrate that PDX-1 and insulin are coexpressed during embryonic development and in adults, although PDX-1 expression appears to be biphasic. Insulin expression apparently begins before 44 hpf, the earliest stage examined in this study. Additionally, very high levels of PDX-1 expression were observed in the pyloric caeca, the accessory digestive organs that also are derived from the proximal region of the intestine in teleosts. Finally, our data show that the evolutionary conservation of zebrafish PDX-1 extends to its DNA binding properties. Zebrafish PDX-1 was equally as effective as mouse PDX-1 in stimulating insulin gene transcription, and maximum promoter activation was dependent on the presence of four intact A elements. The demonstration of this capability suggests that transcriptional regulatory mechanisms that control pancreatic development and insulin gene expression have been conserved among vertebrates.

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32-60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with E-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects (P = 0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.

Background Conventional risk factors of coronary artery disease fail to explain accelerated atherosclerosis in systemic lupus erythematosus (SLE) patients. Clinical and experimental studies shows that soluble intercellular adhesion molecule 1 (sICAM-1) and von Willebrand factor (vWF) levels reflect endothelial damage or dysfunction. Objectives This study was conducted to determine the possible influence of endothelial pathology assessed by sICAM-1 and vWF levels on coronary artery calcifications in SLE patients. Methods In 60 SLE patients in stable clinical conditions, without a prior history of coronary artery disease, MultiDetector Computed Tomography (MDCT)-based coronary calcium scoring was performed. Laboratory evaluation included serum concentrations of sICAM-1, vWF, C-reactive protein (CRP) and antinuclear antibodies (ANA) titers. Results MDCT revealed coronary calcifications in 15 (25%) patients. Calcium scores ranged from 0.3 to 843.2 (median 31,7). No association was found between these scores and conventional coronary artery disease risk factors (obesity, hypertension, tobacco use, hyperlipidaemia, diabetes) nor CRP levels. On the contrary, as compared to patients with calcium score =0, in those with coronary calcifications higher concentrations of sICAM-1 (382.2±328.2 vs. 267.1±62.7, p=0.01), vWF (188.5±87.6 vs. 149.2±52.2, p=0.025) and higher ANA titers (8320±4521 vs. 4668±2717, p=0.03) were found. Conclusions Conventional risk factors of coronary artery disease as well as markers of an ongoing inflammation do not show significant association with coronary artery calcifications in SLE patients. Calcified atherosclerotic plaques were observed mainly in patients with elevated levels of sICAM-1, vWF or high ANA titers. The sICAM-1 and vWF levels may serve as a possible risk marker of coronary calcifications and may have a prognostic importance. Disclosure of Interest None Declared

"Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives. This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution. Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media. Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity. The mechanism of decreased susceptibility to glycopeptide antibiotics among S. aureus derivative isolates is uncertain. The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

Glucose loading tests have provided useful criteria for the diagnosis of gestational diabetes (GDM) (O’Sullivan and Mahan 1964; Gillmer et al. 1980; Barden and Knowles 1981; Carpenter and Coustan 1982). Clinical observations during a 400-kilocalorie meal tolerance test in lean and obese women with GDM have demonstrated heterogeneity in the disorder (Cheney et al. 1985; Hollingsworth et al. 1985), and Freinkel et al. (1986) have described both phenotypic and genotypic heterogeneity in the syndrome.

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted.