Impulsive suicide attempts among young people-A prospective multicentre cohort study in Sweden.

BACKGROUND: We aimed to compare the prevalence of impulsive suicide attempts (ISA) among young adults and those over 25 who present at hospital in connection with attempted suicide. We also aimed to identify factors associated with ISA in young adults and to assess medical severity as well as the probability of repeated suicide attempts in this age group. METHOD: A prospective multicentre cohort study included hospital known cases of suicide attempt (N = 666). The prevalence of ISA was compared between young adults (18-25) and adults aged > 26. We used logistic regression models to identify factors associated with ISA, associations of ISA with high medical severity and prediction of new fatal or non-fatal suicide attempts within 6 months. RESULTS: 43.7% of the young patients had made an ISA, and 30.2% among those aged > 26 (p = 0.001). Among the young, substance use disorder was associated with ISA; crude odds ratio (OR) 2.0 (1.0-4.2), and adjusted OR 2.1 (0.99-4.4). Affective disorder and unemployment/ sickness absence implied lower odds of ISA. ISA resulted in injuries of high medical severity as often as more planned attempts and non-fatal or fatal repetition within 6 months was equally common (30%) in both groups. LIMITATIONS: The study was set in psychiatric emergency services, which limits the generalizability. CONCLUSIONS: Clinicians should acknowledge that suicide attempts among youth often occur without previous planning and may result in medically severe injuries. The probability of new fatal or non-fatal suicide attempts should be kept in mind also after an impulsive suicide attempt.

Mental illness and suicide after self-harm among young adults: long-term follow-up of self-harm patients, admitted to hospital care, in a national cohort.

BACKGROUND: Self-harm among young adults is a common and increasing phenomenon in many parts of the world. The long-term prognosis after self-harm at young age is inadequately known. We aimed to estimate the risk of mental illness and suicide in adult life after self-harm in young adulthood and to identify prognostic factors for adverse outcome. METHOD: We conducted a national population-based matched case-cohort study. Patients aged 18-24 years (n = 13 731) hospitalized after self-harm between 1990 and 2003 and unexposed individuals of the same age (n = 137 310 ) were followed until December 2009. Outcomes were suicide, psychiatric hospitalization and psychotropic medication in short-term (1-5 years) and long-term (>5 years) follow-up. RESULTS: Self-harm implied an increased relative risk of suicide during follow-up [hazard ratio (HR) 16.4, 95% confidence interval (CI) 12.9-20.9). At long-term follow-up, 20.3% had psychiatric hospitalizations and 51.1% psychotropic medications, most commonly antidepressants and anxiolytics. There was a six-fold risk of psychiatric hospitalization (HR 6.3, 95% CI 5.8-6.8) and almost three-fold risk of psychotropic medication (HR 2.8, 95% CI 2.7-3.0) in long-term follow-up. Mental disorder at baseline, especially a psychotic disorder, and a family history of suicide were associated with adverse outcome among self-harm patients. CONCLUSION: We found highly increased risks of future mental illness and suicide among young adults after self-harm. A history of a mental disorder was an important indicator of long-term adverse outcome. Clinicians should consider the substantially increased risk of suicide among self-harm patients with psychotic disorders.

Age-specific suicide mortality following non-fatal self-harm: national cohort study in Sweden.

BACKGROUND: Possible age-related differences in risk of completed suicide following non-fatal self-harm remain unexplored. We examined associations between self-harm and completed suicide across age groups of self-harming patients, and whether these associations varied by violent index method, presence of mental disorder, and repeated self-harm. METHOD: The design was a cohort study with linked national registers in Sweden. The study population comprised individuals aged ⩾10 years hospitalized during 1990-1999 due to non-fatal self-harm (n = 53 843; 58% females) who were followed for 9-19 years. We computed hazard ratios (HRs) across age groups (age at index self-harm episode), with time to completed suicide as outcome. RESULTS: The 1-year HR for suicide among younger males (10-19 years) was 14.6 [95% confidence interval (CI) 4.1-51.9] for violent method and 8.4 (95% CI 1.8-40.0) for mental disorder. By contrast, none of the three potential risk factors increased the 1-year risks in the youngest females. Among patients aged ⩾20 years, the 1-year HR for violent method was 4.6 (95% CI 3.8-5.4) for males and 10.4 (95% CI 8.3-13.0) for females. HRs for repeated self-harm during years 2-9 of follow-up were higher in 10- to 19-year-olds (males: HR 4.0, 95% CI 2.0-7.8; females: HR 3.7, 95% CI 2.1-6.5). The ⩾20 years age groups had higher HRs than the youngest, particularly for females and especially within 1 year. CONCLUSIONS: Violent method and mental disorder increase the 1-year suicide risk in young male self-harm patients. Further, violent method increases suicide risk within 1 year in all age and gender groups except the youngest females. Repeated self-harm may increase the long-term risk more in young patients. These aspects should be accounted for in clinical suicide risk assessment.

Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing.

A study of genome-wide gene expression in major depressive disorder (MDD) was undertaken in a large population-based sample to determine whether altered expression levels of genes and pathways could provide insights into biological mechanisms that are relevant to this disorder. Gene expression studies have the potential to detect changes that may be because of differences in common or rare genomic sequence variation, environmental factors or their interaction. We recruited a European ancestry sample of 463 individuals with recurrent MDD and 459 controls, obtained self-report and semi-structured interview data about psychiatric and medical history and other environmental variables, sequenced RNA from whole blood and genotyped a genome-wide panel of common single-nucleotide polymorphisms. We used analytical methods to identify MDD-related genes and pathways using all of these sources of information. In analyses of association between MDD and expression levels of 13 857 single autosomal genes, accounting for multiple technical, physiological and environmental covariates, a significant excess of low P-values was observed, but there was no significant single-gene association after genome-wide correction. Pathway-based analyses of expression data detected significant association of MDD with increased expression of genes in the interferon α/ß signaling pathway. This finding could not be explained by potentially confounding diseases and medications (including antidepressants) or by computationally estimated proportions of white blood cell types. Although cause-effect relationships cannot be determined from these data, the results support the hypothesis that altered immune signaling has a role in the pathogenesis, manifestation, and/or the persistence and progression of MDD.

AR intragenic deletions linked to androgen receptor splice variant expression and activity in models of prostate cancer progression.

Reactivation of the androgen receptor (AR) during androgen depletion therapy (ADT) underlies castration-resistant prostate cancer (CRPCa). Alternative splicing of the AR gene and synthesis of constitutively active COOH-terminally truncated AR variants lacking the AR ligand-binding domain has emerged as an important mechanism of ADT resistance in CRPCa. In a previous study, we demonstrated that altered AR splicing in CRPCa 22Rv1 cells was linked to a 35-kb intragenic tandem duplication of AR exon 3 and flanking sequences. In this study, we demonstrate that complex patterns of AR gene copy number imbalances occur in PCa cell lines, xenografts and clinical specimens. To investigate whether these copy number imbalances reflect AR gene rearrangements that could be linked to splicing disruptions, we carried out a detailed analysis of AR gene structure in the LuCaP 86.2 and CWR-R1 models of CRPCa. By deletion-spanning PCR, we discovered a 8579-bp deletion of AR exons 5, 6 and 7 in the LuCaP 86.2 xenograft, which provides a rational explanation for synthesis of the truncated AR v567es AR variant in this model. Similarly, targeted resequencing of the AR gene in CWR-R1 cells led to the discovery of a 48-kb deletion in AR intron 1. This intragenic deletion marked a specific CWR-R1 cell population with enhanced expression of the truncated AR-V7/AR3 variant, a high level of androgen-independent AR transcriptional activity and rapid androgen independent growth. Together, these data demonstrate that structural alterations in the AR gene are linked to stable gain-of-function splicing alterations in CRPCa.

The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus.

The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor required for human leukocyte antigens (HLA) class II MHC-restricted antigen presentation. MHC genes, including the HLA class II DRB1*03:01 allele, are strongly associated with systemic lupus erythematosus (SLE). Recently the rs4774 CIITA missense variant (+1632G/C) was reported to be associated with susceptibility to multiple sclerosis. In the current study, we investigated CIITA, DRB1*03:01 and risk of SLE using a multi-stage analysis. In stage 1, 9 CIITA variants were tested in 658 cases and 1363 controls (N=2021). In stage 2, rs4774 was tested in 684 cases and 2938 controls (N=3622). We also performed a meta-analysis of the pooled 1342 cases and 4301 controls (N=5643). In stage 1, rs4774(*)C was associated with SLE (odds ratio (OR)=1.24, 95% confidence interval (95% CI)=1.07-1.44, P=4.2 × 10(-3)). Similar results were observed in stage 2 (OR=1.16, 95% CI=1.02-1.33, P=8.5 × 10(-3)) and the meta-analysis of the combined data set (OR=1.20, 95% CI=1.09-1.33, P(meta)=2.5 × 10(-4)). In all three analyses, the strongest evidence for association between rs4774(*)C and SLE was present in individuals who carried at least one copy of DRB1*03:01 (P(meta)=1.9 × 10(-3)). Results support a role for CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01.

Cadmium, copper, iron, and zinc concentrations in kidneys of grey wolves, Canis lupus, from Alaska, Idaho, Montana (USA) and the Northwest Territories (Canada).

Cadmium, copper, iron, and zinc levels were measured in the kidneys of 115 grey wolves (Canis lupus) from Idaho, Montana and Alaska (United States), and from the Northwest Territories (Canada). No significant differences in the levels of iron or copper were observed between locations, but wolf kidneys from more northern locations had significantly higher cadmium levels (Alaska > Northwest Territories > Montana ≈ Idaho), and wolves from Alaska showed significantly higher zinc than other locations. Additionally, female wolves in Alaska had higher iron levels than males, and adult wolves in Montana had higher copper levels than subadults.

Radiation exposure in stent-grafting of abdominal aortic aneurysms.

In recent years, endovascular stent-grafting of abdominal aortic aneurysms has become more and more common. The radiation dose associated with these procedures is not well documented however. The aim of the present study was to estimate the radiation exposure and to simulate the effects of a switch from C-arm radiographic equipment to a dedicated angiographic suite. Dose-area product (DAP) was recorded for 24 aortic stent-grafting procedures. Based on these data, entrance surface dose (ESD) and effective dose were calculated. A simulation of doses at various settings was also performed using a humanoid Alderson phantom. The image quality was evaluated with a CDRAD contrast-detail phantom. The mean DAP was 72.3 Gy cm(2) at 28 min fluoroscopy time with a mean ESD of 0.39 Gy and a mean effective dose of 10.5 mSv. If the procedures had been performed in an angiographic suite, all dose values would be much higher with a mean ESD of 2.9 Gy with 16 patients exceeding 2 Gy, which is considered to be a threshold for possible skin injury. The image quality for fluoroscopy was superior for the C-arm whilst the angiographic unit gave better acquisition images. Using a C-arm unit resulted in doses similar to percutaneous coronary intervention (PCI). If the same patients had been treated using dedicated angiographic equipment, the risk of skin injury would be much higher. It is thus important to be aware of the dose output of the equipment that is used.

Dose-image optimisation in digital radiology with a direct digital detector: an example applied to pelvic examinations.

In diagnostic radiology increasing attention has been focused on dose reduction while maintaining a clinically good image quality. With the use of digital detectors balancing dose vs image quality is done differently than in film-screen radiography, since dose and image brightness are uncoupled in digital imaging. In this study a new direct digital detector (flat-panel detector) was used in a dose-image optimisation of a simulated pelvic examination. X-ray images were taken with a direct digital detector (DDD), of the pelvic of a phantom using varying tube current (varying stochastic noise). The entrance surface dose was measured for each image. These images were scored by two radiologists according to EU guidelines. A dose comparison was made with an older PCR system (storage phosphor plates). With decreasing tube current the noise in the images increased and the image with the lowest dose and still acceptable image quality was identified. The results showed that the entrance surface dose using the DDD decreased from 1.4 mGy (PCR value) to 0.48 mGy (DDD standard settings). Through the optimisation the dose could be further decreased to 0.24 mGy while still maintaining an acceptable image quality. A substantial dose reduction was obtained with this new direct digital detector. This simple but efficient optimisation approach is easily applicable to other examinations and both DDD and storage phosphor plate detectors.

Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up.

OBJECTIVES: This study evaluated the prognosis of patients resuscitated from ventricular tachycardia (VT) or ventricular fibrillation (VF) with a transient or correctable cause suspected as the cause of the VT/VF. BACKGROUND: Patients resuscitated from VT/VF in whom a transient or correctable cause has been identified are thought to be at low risk for recurrence and often receive no primary treatment for their arrhythmias. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients with a potentially transient or correctable cause of VT/VF were not eligible for randomization. The mortality of these patients was compared with the mortality of patients with a known high risk of recurrence of VT/VF in the AVID registry. RESULTS: Compared with patients having high risk VT/VF, those with a transient or correctable cause for their presenting VT/VF were younger and had a higher left ventricular ejection fraction. These patients were more often treated with revascularization as the primary therapy, more commonly received a beta-blocker, less often required therapy for congestive heart failure and less commonly received either an antiarrhythmic drug or an implantable cardioverter defibrillator. Nevertheless, subsequent mortality of patients with a transient or correctable cause of VT/VF was no different or perhaps even worse than that of the primary VT/VF population. CONCLUSIONS: Patients identified with a transient or correctable cause for their VT/VF remain at high risk for death. Further research is needed to define truly reversible causes of VT/VF. Meanwhile, these patients may require more aggressive evaluation, treatment and follow-up than is currently practiced.

Follow-up of patients with unexplained syncope and inducible ventricular tachyarrhythmias: analysis of the AVID registry and an AVID substudy. Antiarrhythmics Versus Implantable Defibrillators.

INTRODUCTION: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS: Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.

Image quality vs. radiation dose for a flat-panel amorphous silicon detector: a phantom study.

The aim of this study was to investigate the image quality for a flat-panel amorphous silicon detector at various radiation dose settings and to compare the results with storage phosphor plates and a screen-film system. A CDRAD 2.0 contrast-detail phantom was imaged with a flat-panel detector (Philips Medical Systems, Eindhoven, The Netherlands) at three different dose levels with settings for intravenous urography. The same phantom was imaged with storage phosphor plates at a simulated system speed of 200 and a screen-film system with a system speed of 160. Entrance surface doses were recorded for all images. At each setting, three images were read by four independent observers. The flat-panel detector had equal image quality at less than half the radiation dose compared with storage phosphor plates. The difference was even larger when compared with film with the flat-panel detector having equal image quality at approximately one-fifth the dose. The flat-panel detector has a very favourable combination of image quality vs radiation dose compared with storage phosphor plates and screen film.

Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation.

BACKGROUND: The purpose of this study was to determine how often accessory atrioventricular (AV) pathways (AP) cross the AV groove obliquely. With an oblique course, the local ventriculoatrial (VA) interval at the site of earliest atrial activation (local-VA) and the local-AV interval at the site of earliest ventricular activation (local-AV) should vary by reversing the direction of the paced ventricular and atrial wavefronts, respectively. METHODS AND RESULTS: One hundred fourteen patients with a single AP were studied. Two ventricular and two atrial pacing sites on opposite sides of the AP were selected to reverse the direction of the ventricular and atrial wavefronts along the annulus. Reversing the ventricular wavefront increased local-VA by >/=15 ms in 91 of 106 (91%) patients. With the shorter local-VA, the ventricular potential overlapped the atrial potential along a 17.2+/-8.5-mm length of the annulus. No overlap occurred with the opposite wavefront. Reversing the atrial wavefront increased local-AV by >/=15 ms in 32 of 44 (73%) patients. With the shorter local-AV, the atrial potential overlapped the ventricular potential along an 11.9+/-8.9-mm length of the annulus. No overlap occurred with the opposite wavefront. Mapping during longer local-VA or local-AV identified an AP potential in 102 of 114 (89%) patients. Catheter ablation eliminated AP conduction in all 111 patients attempted (median, 1 radiofrequency application in 99 patients with an AP potential versus 4.5 applications without an AP potential). CONCLUSIONS: Reversing the direction of the paced ventricular or atrial wavefront reveals an oblique course in most APs and facilitates localization of the AP potential for catheter ablation.

Unexpectedly high defibrillation thresholds in an active can implantable cardioverter defibrillator system.

This case report describes a patient undergoing defibrillator generator replacement in whom the defibrillation thresholds were significantly higher with a can-active system than with a non-active can system.

Electrical storm presages nonsudden death: the antiarrhythmics versus implantable defibrillators (AVID) trial.

BACKGROUND: Electrical storm, multiple temporally related episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), is a frequent problem among recipients of implantable cardioverter defibrillators (ICDs). However, insufficient data exist regarding its prognostic significance. METHODS AND RESULTS: This analysis includes 457 patients who received an ICD in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial and who were followed for 31 +/- 13 months. Electrical storm was defined as > or = 3 separate episodes of VT/VF within 24 hours. Characteristics and survival of patients surviving electrical storm (n = 90), those with VT/VF unrelated to electrical storm (n = 184), and the remaining patients (n = 183) were compared. The 3 groups differed in terms of ejection fraction, index arrhythmia, revascularization status, and baseline medication use. Survival was evaluated using time-dependent Cox modeling. Electrical storm occurred 9.2 +/- 11.5 months after ICD implantation, and most episodes (86%) were due to VT. Electrical storm was a significant risk factor for subsequent death, independent of ejection fraction and other prognostic variables (relative risk [RR], 2.4; 95% confidence interval [CI], 1.3 to 4.2; P = 0.003), but VT/VF unrelated to electrical storm was not (RR, 1.0; 95% CI, 0.6 to 1.7; P = 0.9). The risk of death was greatest 3 months after electrical storm (RR, 5.4; 95% Cl, 2.4 to 12.3; P = 0.0001) and diminished beyond this time (RR, 1.9; 95% CI, 1.0 to 3.6; P=0.04). CONCLUSIONS: Electrical storm is an important, independent marker for subsequent death among ICD recipients, particularly in the first 3 months after its occurrence. However, the development of VT/VF unrelated to electrical storm does not seem to be associated with an increased risk of subsequent death.

Transseptal left heart catheterization for cardiac ablation procedures.

UNLABELLED: Transseptal left heart catheterization has been performed as an alternative to the retrograde approach since 1958. However, this procedure can result in life-threatening complications, some of which may occur because of insufficient anatomical landmarks. Accordingly, we sought to assess the safety and efficacy of a new transseptal left heart catheterization technique designed for ablation procedures. Specifically, we examined whether electrode catheters could be used as anatomical landmarks, permitting identification of the aortic root and other critical structures. RESULTS: One hundred and eight consecutive patients underwent transseptal left heart catheterization under biplane fluoroscopy during catheter ablation. Electrode catheters positioned in the right atrial appendage, His bundle region, and coronary sinus were used as anatomical landmarks to guide the transseptal unit to the fossa ovalis. The angles of the right anterior and left anterior oblique projections were selected in each patient based on the orientation of the His bundle and coronary sinus catheters. Transseptal left heart catheterization was successfully performed in all patients without complications. In contrast to previous reports, the direction of the needle at the successful puncture site in the last 96 patients varied substantially: 2 o'clock in 13 patients (13 %); 3 o'clock in 43 patients (45 %); and 4 o'clock in 40 patients (42 %). CONCLUSION: The use of electrode catheters as anatomical landmarks and biplane fluoroscopy facilitates transseptal catheterization. This approach can be used safely during catheter ablation procedures.

Digital radiography of scoliosis with a scanning method: initial evaluation.

PURPOSE: To evaluate the radiation dose, image quality, and Cobb angle measurements obtained with a digital scanning method of scoliosis radiography. MATERIALS AND METHODS: Multiple images were reconstructed into one image at a workstation. A low-dose alternative was to use digital pulsed fluoroscopy. Dose measurements were performed with thermoluminescent dosimeters in an Alderson phantom. At the same time, kerma area-product values were recorded. A Monte Carlo dose calculation also was performed. Image quality was evaluated with a contrast-detail phantom and visual grading system. Angle measurements were evaluated with an angle phantom and measurements obtained on patient images. RESULTS: The effective radiation dose was 0.087 mSv for screen-film imaging, 0.16 mSv for digital exposure imaging, and 0.017 mSv for digital fluoroscopy; the corresponding kerma area-product values were 0.43, 0.87, and 0.097 Gy. cm(2), respectively. The image quality of the digital exposure and screen-film images was about equal at visual grading, whereas fluoroscopy had lower image quality. The angle phantom had lower angle values with digital fluoroscopy, although the difference in measured angles was less than 0.5 degrees. The patient images showed no difference in angles. CONCLUSION: The described digital scanning method has acceptable image quality and adequate accuracy in angle measurements. The radiation dose required for digital exposure imaging is higher than that required for screen-film imaging, but that required for digital fluoroscopy is much lower.

Characterization of reentrant circuit in macroreentrant right atrial tachycardia after surgical repair of congenital heart disease: isolated channels between scars allow "focal" ablation.

BACKGROUND: The purpose of this study was to characterize the circuit of macroreentrant right atrial tachycardia (MacroAT) in patients after surgical repair of congenital heart disease (SR-CHD). METHODS AND RESULTS: Sixteen patients with atrial tachycardia (AT) after SR-CHD were studied (atrial septal defect in 6, tetralogy of Fallot in 4, and Fontan procedure in 6). Electroanatomic right atrial maps were obtained during 15 MacroATs in 13 patients, focal AT in 1 patient, and atrial pacing in 2 patients without stable AT. A large area of low bipolar voltage (/=2 scars forming narrow channels. Ablation within the channels eliminates MacroAT.

A simpler, more robust method for the analysis of 8-oxoguanine in DNA.

The oxidized DNA base 8-oxoguanine has been commonly measured by enzymatic digestion of DNA to nucleosides followed by high-performance liquid chromatography (HPLC) separation of the adduct 8-oxodeoxyguanosine. There has recently been an enormous debate surrounding the validity of this approach, from which it has become clear that artifactual oxidation of the native base to 8-oxoguanine can occur at numerous stages in sample preparation. Hence, we have designed an alternative protocol to traditional enzymatic digestion of DNA which (i) limits the potential for artifactual oxidation, (ii) speeds up the assay markedly, (iii) increases the assay's sensitivity moderately, and (iv) addresses criticisms that have been raised concerning the efficiency of DNA digestion by nucleases. In short, we use the Escherichia coli repair enzyme formamidopyrimidine (Fapy) glycosylase to release the base 8-oxoguanine from full-length DNA, then separate 8-oxoguanine from high molecular weight molecules by ultrafiltration (10,000 Da exclusion) and analyze the base adduct by reverse-phase HPLC. Benefits of this approach include (i) rapid removal of the roughly million-fold molar excess of unaltered bases from the sample, (ii) reduction in the length of enzymatic incubations and the number of steps, (iii) elimination of high temperature incubation, (iv) a very clean chromatographic separation, and (v) rapid elution of the analyte and correspondingly greater throughput. Using this improved method, we have followed the induction of 8-oxoguanine in the DNA of peroxide-treated HeLa cells, an experiment that had proved cumbersome with traditional methods.

Nationwide standardisation and evaluation of scintigraphic gastric emptying: reference values and comparisons between subgroups in a multicentre trial.

By means of a standardised procedure, reference values for scintigraphic gastric emptying were established. The influence of gender, age, menstrual cycle, body mass index (BMI) and smoking habits was also evaluated. Eight centres recruited 20 healthy subjects each. The meal consisted of a technetium-99m labelled omelet (1,300 kJ) and of 150 ml unlabelled soft drink. Geometric means of frontal and dorsal acquisitions were utilised in a linear fit model for determination of the linear emptying rate, and by using the intercepts of the regression line with the 90% and 50% levels, the lag phase and half-emptying time, respectively, were defined. All individuals showed an initial lag phase and subsequent linear emptying. Because of a longer lag phase and a slower linear emptying rate, premenopausal women had a slower gastric emptying than postmenopausal women and men of all ages. The gastric emptying rate increased with age in the women, mainly due to a shortened lag phase, while the emptying rate remained almost unchanged with age in the males. There were no significant differences in results between the centres. The menstrual cycle, BMI and smoking habits did not affect emptying. In conclusion, the fact that the results showed a slower gastric emptying rate in younger women compared with older women and men indicates that it is necessary to use separate reference values for fertile females.