Characterisation of patients referred to a tertiary-level inherited cardiac condition clinic with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC).

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic cardiomyopathy is a rare inherited disease with incomplete penetrance and an environmental component. Although a rare disease, ARVC is a common cause of sudden cardiac death in young adults. Data on the different stages of ARVC remains scarce. The purpose of this study is to describe the initial presentation and cardiac phenotype of definite and non-definite ARVC for patients seen at a tertiary service. METHODS: This is a single centre, observational cohort study of patients with definite and non-definite ARVC seen at the Inherited Cardiac Conditions services at University Hospital Birmingham (UHB) in the period 2010-2021. Patients were identified by interrogation of digital health records, medical history, imaging and by examining 12-lead electrocardiograms (ECG). RESULT: The records of 1451 patients were reviewed; of those, 165 patients were at risk of ARVC (mean age 41 ± 17 years, 56% male). 60 patients fulfilled task force criteria for definite ARVC diagnosis (n = 40, 67% males), and 38 (72%) of them carried a known pathogenic variant. The remaining 105 patients (50% males) were non-definite, and of these 45 (62%) carried a known pathogenic variant. Patients in the definite group were more symptomatic, with palpitations (57% vs. 17%), syncope (35% vs. 6%) and shortness of breath (28% vs. 5%, p < 0.001). T-wave inversion in V1-V3 and epsilon waves were observed only in the definite group. Both PR interval and QRS duration were longer in the definite (170 ± 34 ms and 100 ± 19 ms, p < 0.001) compared to (149 ± 25 and 91 ± 14 ms, p = 0.005). Patients with definite ARVC had significantly larger RV end diastolic areas and significantly reduced biventricular function (RVEDA = 27 ± 10 cm2, RVFAC = 37 ± 11% and EF = 56 ± 12%) compared to the non-definite group (RVEDA = 18 ± 4 cm2, RVFAC 49 ± 6% and LVEF 64 ± 7%, p < 0.001). Sustained ventricular tachycardia (VT) occurred more frequently in the definite group compared to the non-definite group (27% vs. 2%, p < 0.001). Ventricular fibrillation was observed in the definite group only (8 of 60 patients, 13%). CONCLUSION: Our study showed differences between definite and non-definite ARVC patients in terms of clinical, electrophysiological and imaging features. Major adverse cardiac events occurred more commonly in the definite group, but also were observed in non-definite ARVC. This single centre observational cohort study forms a basis for further prospective multicentre interventional studies.

Opportunities from a new disease for an old threat: Extending COVID-19 efforts to address tuberculosis in South Africa.

The COVID-19 pandemic and phased nationwide lockdown have impacted negatively on individuals with tuberculosis (TB) and routine TB services. Through a literature review and the perspective of members of a national TB Think Tank task team, we describe the impact of the pandemic and lockdown on TB patients and services as well as the potential long-term setback to TB control in South Africa (SA). Strategies to mitigate risk and impact are explored, together with opportunities to leverage synergies from both diseases to the benefit of the National TB Programme (NTP). With the emergence of COVID-19, activities to address this new pandemic have been prioritised across all sectors. Within the health system, the health workforce and resources have been redirected away from routine services towards the new disease priority. The social determinants of health have deteriorated during the lockdown, potentially increasing progression to TB disease and impacting negatively on people with TB and their households, resulting in additional barriers to accessing TB care, with early reports of a decline in TB testing rates. Fewer TB diagnoses, less attention to adherence and support during TB treatment, poorer treatment outcomes and consequent increased transmission will increase the TB burden and TB-related mortality. People with TB or a history of TB are likely to be vulnerable to COVID-19. Modifications to current treatment practices are suggested to reduce visits to health facilities and minimise the risks of COVID-19 exposure. The COVID-19 pandemic has the potential to negatively impact on TB control in TB-endemic settings such as SA. However, there are COVID-19-related health systems-strengthening developments that may help the NTP mitigate the impact of the pandemic on TB control. By integrating TB case finding into the advanced screening, testing, tracing and monitoring systems established for COVID-19, TB case finding and linkage to care could increase, with many more TB patients starting treatment. Similarly, integrating knowledge and awareness of TB into the increased healthcare worker and community education on infectious respiratory diseases, behavioural practices around infection prevention and control, and cough etiquette, including destigmatisation of mask use, may contribute to reducing TB transmission. However, these potential gains could be overwhelmed by the impact of increasing poverty and other social determinants of health on the burden of TB.

Mucosal glucagon-like peptide 1 (GLP-1) responses are mediated by calcitonin gene-related peptide (CGRP) in the mouse colon and both peptide responses are area-specific.

BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice. METHODS: A tissue survey of GLP-1 responses (using exendin 4, Ex4) and α-calcitonin gene-related peptide (αCGRP) was undertaken, dividing the mouse colon into eight adjacent mucosal-submucosal preparations. Each preparation was voltage-clamped and changes in short-circuit current (Isc) measured. The involvement of submucosal neurons in GLP-1 agonism was tested using Ex(9-39) and tetrodotoxin (TTX), and CGRP receptors were blocked with BIBN4094. KEY RESULTS: Ex4 responses along the length of the colon were inhibited by the GLP-1 antagonist, Ex(9-39) or TTX, indicating neural mediation in all colonic regions. In the ascending colon, Ex4 increased Isc levels that were abolished by 10 nM BIBN4096, while in the descending colon it reduced Isc levels that were again BIBN4096-sensitive, but at 1 µM. The latter αCGRP response was dependent on epithelial Cl- conductance and Na+ /K+ -ATPase, and was partially (~25%) peptide YY-mediated, but was not nitrergic, somatostatin sst2 , or α2 -adrenoceptor-mediated. CONCLUSIONS AND INFERENCES: GLP-1 modulates epithelial ion transport indirectly by activating CGRP-containing submucosal enteric neurons in the mouse colon. This GLP-1-CGRP response was area-specific and could potentially contribute to the diarrheal side effect of certain GLP-1R therapeutics.

Missed opportunities for earlier diagnosis of rifampicin-resistant tuberculosis despite access to Xpert® MTB/RIF.

OBJECTIVE: To assess the proportion of rifampicin-resistant tuberculosis (RR-TB) patients with potential earlier RR-TB diagnoses in Khayelitsha, South Africa. DESIGN: We conducted a retrospective analysis among RR-TB patients diagnosed from 2012 to 2014. Patients were considered to have missed opportunities for earlier diagnosis if 1) they were incorrectly screened according to the Western Cape diagnostic algorithm; 2) the first specimen was not tested using Xpert® MTB/RIF; 3) no specimen was ever tested; or 4) the initial Xpert test showed a negative result, but no subsequent specimen was sent for follow-up testing in human immunodeficiency virus-positive patients. RESULTS: Among 543 patients, 386 (71%) were diagnosed with Xpert and 112 (21%) had had at least one presentation at a health care facility within the 6 months before the presentation at which RR-TB was diagnosed. Overall, 95/543 (18%) patients were screened incorrectly at some point: 48 at diagnostic presentation only, 38 at previous presentation only, and 9 at both previous and diagnostic presentations. CONCLUSIONS: These data show that a significant proportion of RR-TB patients might have been diagnosed earlier, and suggest that case detection could be improved if diagnostic algorithms were followed more closely. Further training and monitoring is required to ensure the greatest benefit from universal Xpert implementation.

Effects of electromagnetic fields emitted by GSM phones on working memory: a meta-analysis.

BACKGROUND AND OBJECTIVE: Current treatments for Alzheimer's Disease (AD) do not affect the course of the illness and brain stimulation techniques are increasingly promoted as potential therapeutic interventions for AD. This study reviews the effects of electromagnetic field (EMF) exposure versus sham exposure on working memory (WM) performance of healthy human participants. METHOD: Online literature databases and previous systematic reviews were searched for studies of EMF and WM in participants without reported memory problems. Two thousand eight hundred and fifty seven studies were identified, and 10 studies met the inclusion criteria. An assessment of study quality was completed, and separate, random effects meta-analyses were conducted for each of the three WM tasks included: n-back, substitution and digit span forward. RESULTS: No differences were found between participants exposed to active EMF versus sham conditions in any of the three working memory tasks examined. CONCLUSION: Results indicate that EMF does not affect WM during the n-back, substitution and digit-span tasks. Future studies should focus on the possible effects of chronic exposure to EMF in older adults with AD using a battery of comparable WM and attention tasks, before EMF can be seriously considered as a potential modulator of WM in AD. Copyright © 2016 John Wiley & Sons, Ltd.

High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice.

BACKGROUND AND PURPOSE: Human pancreatic polypeptide (hPP) is known to suppress appetite and food intake, thereby representing a potential therapeutic approach against obesity and associated metabolic disorders. The aim of this study was to improve hPP stability by covalent PEGylation with diverse molecular weight polyethylene glycols (PEGs) at two positions using promising lead structures while maintaining target activity. EXPERIMENTAL APPROACH: Modified peptides were synthesized by combined solid-phase and solution-phase peptide synthesis. Their potency was investigated in constitutively expressing human epithelial cells and isolated human colonic mucosa as well as receptor-transfected artificial cell lines. Human blood plasma and porcine liver homogenates were used to examine the in vitro stability of the analogues. The most promising variants were injected s.c. in C57BL/6JRj mice to monitor fasting-induced food intake and bioavailability. KEY RESULTS: In human epithelia and colonic mucosal preparations, activity of the modified hPP peptides depended on the core sequence and latency of the peptides was related to PEG size. Peptides modified with a 22 kDa PEG (PEG22) remained intact in blood plasma and on incubation with liver homogenates for more than 96 h. Finally, hPP2-36 , [K22 (PEG22)]hPP2-36 and [K22 (PEG22),Q34 ]hPP significantly reduced cumulative food intake in mice over 16 h after s.c. administration. CONCLUSIONS AND IMPLICATIONS: Modification with PEG22 at position 22 stabilizes hPP significantly while extending its biological activities and could be used in drug development prospectively.

A single-center experience with infections due to daptomycin-nonsusceptible Enterococcus faecium in liver transplant recipients.

BACKGROUND: Infections caused by vancomycin-resistant Enterococcus faecium (VRE) are a major cause of morbidity and mortality in the liver transplant population. Daptomycin (DAP) is often used to treat infections caused by VRE, but DAP nonsusceptibility in Enterococcus is increasing. METHOD: Patients with DAP-nonsusceptible Enterococcus (DNSE) infections who had undergone liver transplantation between January 1, 2010 and July 31, 2014 were retrospectively reviewed. A convenience sample of DNSE isolates was analyzed by pulsed-field gel electrophoresis (PFGE). RESULTS: We identified 14 liver transplant recipients (LTRs) who developed DNSE infections post transplantation. Postoperative complications were common, and most patients required repeat abdominal surgery within 90 days of transplantation. The initial DNSE culture was taken a median of 74.5 days post transplant and was secondary to an intra-abdominal infection in all but 1 patient. Half of patients were VRE colonized before or at the time of organ transplantation, and all those who were not VRE colonized at the time of transplantation later became colonized, a median of 27 days post transplant. Overall mortality in this cohort was 71%. PFGE did not demonstrate genetic relatedness among DNSE isolates. CONCLUSION: This study, the largest published series to our knowledge of DNSE infections in LTRs, demonstrates that these infections occur in patients with serious surgical complications and are associated with high morbidity and mortality. Established risk factors for VRE infection were common, as was DAP exposure. Although many risk factors for DNSE infection cannot be changed, this case series identifies several potentially modifiable variables. Further work is needed to identify interventions to decrease the risk of developing DNSE infections in this complex patient population.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients. METHODS: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis. RESULTS: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21-0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL(high)=96%, HPV-positive/TIL(low)=59%). Survival of HPV-positive/TIL(low) patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a 'training' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82). INTERPRETATION: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

Use of complementary markers in assessing glycaemic control in people with diabetic kidney disease undergoing iron or erythropoietin treatment.

AIMS: HbA(1c) values are unreliable in patients with diabetes who have chronic kidney disease who receive iron and/or erythropoiesis stimulating agents. The study aimed to evaluate the utility of the complementary glycaemic markers glycated albumin, fructosamine and 1,5 anhydroglucitol in this group of patients. METHODS: A prospective study of patients with Type 2 diabetes and chronic kidney disease stage IIIB/IV undergoing intravenous iron or erythropoiesis-stimulating agent therapy. Glycaemic control was monitored using HbA(1c), seven-point daily glucose thrice weekly, continuous glucose monitoring, glycated albumin, fructosamine and 1,5 anhydroglucitol. RESULTS: Fifteen patients [9 men; median age 72 years (interquartile range 68-74), follow-up period (16.4 ± 3.7 weeks)] received parenteral iron; 15 patients [11 men; 70 years (interquartile range 62-75), (17.3 ± 3.3 weeks)] received erythropoiesis-stimulating agent. HbA(1c) fell following treatment with both iron [57 mmol/mol (7.4%) to 53 mmol/mol (7.0%), P < 0.001] and erythropoiesis-stimulating agent [56 mmol/mol (7.3%) to 49 mmol/mol (6.6%), P = 0.01] despite mean blood glucose remaining unchanged (iron: 9.55 to 9.71 mmol/l, P = 0.07; erythropoiesis-stimulating agent: 8.72 to 8.78 mmol/l, P = 0.89). Unlike HbA1c , the glycated albumin, fructosamine and 1,5 anhydroglucitol levels did not change following iron [glycated albumin (16.8 to 16.3%, P = 0.10); fructosamine (259.5 to 256 µmol/l, P = 0.89); 1,5 anhydroglucitol (54.2 to 50.9 µmol/l, P = 0.89)] or erythropoiesis-stimulating agent [glycated albumin (17.9 to 17.5%, P = 0.29), fructosamine (324.3 to 306.0 µmol/l, P = 0.52), 1,5 anhydroglucitol (58.2 to 46.7 µmol/l, P = 0.35)]. Despite this, HbA(1c) was consistently the marker most closely related to mean blood glucose before and after each treatment (R range 0.7-0.88). CONCLUSIONS: These data indicate that HbA(1c) was statistically most closely related to mean blood glucose, but clinical trends in glycaemia in patients undergoing iron or erythropoiesis-stimulating agent therapy are likely best assessed by including one of these additional glycaemic markers.

A brief cognitive behavioural preimplantation and rehabilitation programme for patients receiving an implantable cardioverter-defibrillator improves physical health and reduces psychological morbidity and unplanned readmissions.

OBJECTIVE: To assess the clinical and cost effectiveness of a brief home-based cognitive behavioural rehabilitation programme (the ICD Plan) for patients undergoing implantation of a cardiac defibrillator. DESIGN: A prospective multicentred, intention-to-treat, cluster-randomised controlled trial. SETTING: Eight implantable cardioverter-defibrillator (ICD) implantation centres in the UK. PATIENTS: Consecutive series of patients undergoing implantation with an ICD. INTERVENTIONS: The control group received usual care and advice from an experienced healthcare professional. The intervention group received usual care plus the ICD Plan. The plan was introduced before implantation, with three further brief telephone contacts with the nurse over the next 12 weeks. MAIN OUTCOME MEASURES: Health-related quality of life (Short Form Health Survey (SF-12)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), activity limitations (subscale from the Seattle Angina Questionnaire (SAQ)), unplanned admissions and other economic data using a questionnaire developed for the study. RESULTS: 192 patients were recruited to the study (71 intervention, 121 control). At 6 months after surgery the intervention group had better physical health (37.83 vs 34.24; p<0.01), fewer limitations in physical activity (34.02 vs 31.72; p = 0.04), a greater reduction in the proportion of patients with a borderline diagnosis of anxiety (21% vs 13%; p = 0.60) and depression (13% vs 2%; p = 0.30), more planned ECGs (89% vs 66%; p = 0.04) and 50% fewer unplanned admissions (11% vs 22%; p<0.01). CONCLUSIONS: The ICD Plan improved health-related quality of life, reduced the incidence of clinically significant psychological distress and significantly reduced unplanned readmissions. It is a cost effective and easily implemented method for delivering rehabilitation and psychological care to patients undergoing ICD implantation. TRIAL REGISTRATION NUMBER: ISRCTN70212111.

Linkage mapping of CVD risk traits in the isolated Norfolk Island population.

To understand the underlying genetic architecture of cardiovascular disease (CVD) risk traits, we undertook a genome-wide linkage scan to identify CVD quantitative trait loci (QTLs) in 377 individuals from the Norfolk Island population. The central aim of this research focused on the utilization of a genetically and geographically isolated population of individuals from Norfolk Island for the purposes of variance component linkage analysis to identify QTLs involved in CVD risk traits. Substantial evidence supports the involvement of traits such as systolic and diastolic blood pressures, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, body mass index and triglycerides as important risk factors for CVD pathogenesis. In addition to the environmental influences of poor diet, reduced physical activity, increasing age, cigarette smoking and alcohol consumption, many studies have illustrated a strong involvement of genetic components in the CVD phenotype through family and twin studies. We undertook a genome scan using 400 markers spaced approximately 10 cM in 600 individuals from Norfolk Island. Genotype data was analyzed using the variance components methods of SOLAR. Our results gave a peak LOD score of 2.01 localizing to chromosome 1p36 for systolic blood pressure and replicated previously implicated loci for other CVD relevant QTLs.

A functional comparison of recombinant and native somatostatin sst2 receptor variants in epithelia.

BACKGROUND AND PURPOSE: Somatostatin (SRIF-14) exerts broad spectrum antisecretory effects by activating the somatostatin 2 (sst(2)) receptor. The rat (r) sst(2) receptor exists in 'long' (sst(2a)) and 'short' (sst(2b)) forms that differ in their C termini, while a single human (h) sst(2a) exists. This study compares the characteristics of recombinant rsst(2a), rsst(2b) and hsst(2a) activation in human epithelia, and with native sst(2) responses in rat colon. EXPERIMENTAL APPROACH: Epithelial layers of each clone or rat colon were placed in Ussing chambers and short-circuit current (I (SC)) measured in response to SRIF-14 and chosen analogues. The relative potencies and ability to cause desensitization to SRIF-14 were assessed, and the affinities of the sst(2) antagonist, D-Tyr(8) CYN154806 for hsst(2a), rsst(2a) and native rat colon sst(2) receptors were established. KEY RESULTS: Basolateral SRIF-14 responses were transient in hsst(2a) and rsst(2a) epithelia, but prolonged in rsst(2b)-expressing cells. Activation of rsst(2a) resulted in significant desensitization to SRIF-14 and receptor phosphorylation, whereas the rsst(2b) receptor did neither. Sst(2)-preferred agonists (BIM23190C and BIM23027) reduced I (sc) with similar potency and both caused complete desensitization to SRIF-14. CYN154806 antagonized hsst(2a) and rsst(2a) receptors with pK (B) values of 7.9 and 7.8, respectively. In rat colon mucosa, CYN154806 blocked SRIF-14 responses with a pA (2) value of 8.2, and BIM23190C responses with a pK (B) of 8.4. CONCLUSIONS AND IMPLICATIONS: SRIF-14 caused rapid rsst(2a) receptor phosphorylation and desensitization of epithelial antisecretory responses, neither of which occurred with the rsst(2b) receptor. These mechanisms are most likely to be a prerequisite for sensitivity to sst(2)-analogues with radiotherapeutic potential.

Odor and volatile organic compound removal from wastewater treatment plant headworks ventilation air using a biofilter.

Laboratory-scale experiments and field studies were performed to evaluate the feasibility of biofilters for sequential removal of hydrogen sulfide and volatile organic compounds (VOCs) from wastewater treatment plant waste air. The biofilter was designed for spatially separated removal of pollutants to mitigate the effects of acid production resulting from hydrogen sulfide oxidation. The inlet section of the upflow units was designated for hydrogen sulfide removal and the second section was designated for VOC removal. Complete removal of hydrogen sulfide (H2S) and methyl tert-butyl ether (MTBE) was accomplished at loading rates of 8.3 g H2S/(m3 x h) (15-second empty bed retention time [EBRT]) and 33 g MTBE/(m3 x h) (60-second EBRT), respectively. In field studies performed at the Hyperion Treatment Plant in Los Angeles, California, excellent removal of hydrogen sulfide, moderate removal of nonchlorinated VOCs such as toluene and benzene, and poor removal of chlorinated VOCs were observed in treating the headworks waste air. During spiking experiments on the headworks waste air, the percentage removals were similar to the unspiked removals when nonchlorinated VOCs were spiked; however, feeding high concentrations of chlorinated VOCs reduced the removal percentages for all VOCs. Thus, biofilters offer a distinct advantage over chemical scrubbers currently used at publicly owned treatment works in that they not only remove odor and hydrogen sulfide efficiently at low cost, but also reduce overall toxicity by partially removing VOCs and avoiding the use of hazardous chemicals.

Inhalation aromatherapy during radiotherapy: results of a placebo-controlled double-blind randomized trial.

PURPOSE: To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety. PATIENTS AND METHODS: Three hundred thirteen patients undergoing radiotherapy were randomly assigned to receive either carrier oil with fractionated oils, carrier oil only, or pure essential oils of lavender, bergamot, and cedarwood administered by inhalation concurrently with radiation treatment. Patients underwent assessment by the Hospital Anxiety and Depression Scale (HADS) and the Somatic and Psychological Health Report (SPHERE) at baseline and at treatment completion. RESULTS: There were no significant differences in HADS depression or SPHERE scores between the randomly assigned groups. However, HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms (P =.04). CONCLUSION: Aromatherapy, as administered in this study, is not beneficial.

Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon mucosa.

A functional study has been performed to characterise the Y receptors responsible for NPY, PYY and PP-stimulated responses in mouse colonic mucosal preparations. Electrogenic ion secretion was stimulated with VIP following which NPY, PYY and PP analogues were, to varying degrees, inhibitory. PYY(3-36), hPP, Gln(23)hPP and rPP were effective but less potent than full length PYY, NPY or their Pro(34)-substituted analogues, while the Y(5) agonist Ala(31), Aib(32)hNPY was the least active peptide tested. The Y(1) antagonists, BIBP3226 and BIBO3304 virtually abolished Pro(34)PYY and PYY responses while PYY(3-36) responses were selectively inhibited by the Y(2) antagonist, BIIE0246. A combination of BIBO3304 and BIIE0246 also partially attenuated hPP responses, leaving residual effects that were most probably Y(4)-mediated. Thus we conclude that Y(1), Y(2) and Y(4) receptors attenuate ion secretion in mouse colon.

Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice.

To further examine the function of the trefoil factor family (TFF), the expression of which is up-regulated at sites of injury, we have produced transgenic mice that chronically express rat TFF3 within the jejunum (using a rat fatty acid-binding protein promoter). The expression of rat TFF3 was limited to the villi of the jejunum and had no effect on base-line morphology. Rat TFF3 expression did result, however, in a reduced sensitivity to indomethacin (85 mg/kg subcutaneously), which only caused a 29% reduction in villus height in transgenics versus 51% reduction in controls (p < 0.01). Indomethacin increased initial intestinal epithelial cell proliferation and migration, but the presence of rat TFF3 caused no additional change in proliferation (bromodeoxyuridine), cell migration ([(3)H]thymidine and bromodeoxyuridine), apoptosis (terminal deoxyuridine nucleotidyl nick end labeling), or E-cadherin immunostaining. In vitro studies following changes in resistance of intestinal strips in Ussing chambers (voltage-clamp technique) showed increased base-line resistance in the rat TFF3-expressing region (326 +/- 60 versus 195 +/- 48 ohm.cm(2) in controls, p < 0.05) and reduced the fall in resistance following HCl exposure by about 40% (p < 0.01). Overexpression of TFF3 stabilizes the mucosa against noxious agents, supporting its role in mucosal protection/repair. It may therefore provide a novel approach to the prevention and/or treatment of intestinal ulceration.

Parents' accounts of obtaining a diagnosis of childhood cancer.

BACKGROUND: Quick diagnosis and treatment of cancers is a UK government priority. However, the process of arriving at a diagnosis of childhood cancer has been neglected in comparison with the attention given to cancers in adults. We investigated parents' narratives about the period before their child's diagnosis. METHODS: We undertook semistructured interviews with 20 parents whose children (aged 4-18 years) had a confirmed diagnosis of cancer or brain tumour. All interviews were recorded and fully transcribed. Dates of consultations and investigations were noted from children's medical records. Data were analysed by the constant comparison method. FINDINGS: The time before diagnosis is very significant for parents and might affect their adaptation and reaction to their child's diagnosis. Parents were first alerted to their child's illness by a range of signs and symptoms, and by behavioural and affective changes. These early symptoms were often vague, non-specific, and common, and some older children were reluctant to disclose symptoms. Ten families' accounts of this period before diagnosis included a dispute with doctors. Disagreements between parents and doctors about the seriousness of children's symptoms and the need for investigations occurred in both primary and secondary care. Some parents felt that doctors discounted their special knowledge of their child. INTERPRETATION: Parents' accounts offer valuable insights into their experiences of obtaining a diagnosis of childhood cancer and into possible sources of delays in this complex process. If delays are to be avoided or reduced, attention must be given to the different roles of parents, children, general practitioners, hospital specialists, and type of cancer. Our findings have important implications for policy, practice, and research, and for the management of childhood illnesses.