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1.
Eur Heart J ; 43(47): 4872-4883, 2022 12 14.
Article in English | MEDLINE | ID: mdl-36030464

ABSTRACT

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS AND RESULTS: The PRAETORIAN trial is an international, multicentre, randomized trial in which 849 patients with an indication for ICD therapy were randomized to receive an S- ICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections, and the need for invasive interventions. Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group, 49 complications occurred in 44 patients of which lead dysfunction was most frequent (HR: 0.69; P = 0.11). In both groups, half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared with the TV-ICD group (P < 0.001, P = 0.03, respectively). Significantly more complications required invasive interventions in the TV-ICD group compared with the S-ICD group (8.3% vs. 4.3%, HR: 0.59; P = 0.047). CONCLUSION: This secondary analysis shows that lead-related complications and systemic infections are more prevalent in the TV-ICD group compared with the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision-making in clinical practice.


Subject(s)
Death, Sudden, Cardiac , Defibrillators, Implantable , Humans , Treatment Outcome , Defibrillators, Implantable/adverse effects
2.
Am Heart J ; 253: 53-58, 2022 11.
Article in English | MEDLINE | ID: mdl-35850242

ABSTRACT

This was a head-to-head comparative study on different electrocardiogram (ECG)-based smartwatches and devices for atrial fibrillation detection. We prospectively included 220 patients scheduled for electrical cardioversion and recorded ECGs with 3 different devices (Withings Move ECG, Apple Watch 5, Kardia Mobile 6-leads) as well as the standard 12-lead ECG (gold standard), both before and after cardioversion. All atrial fibrillation detection algorithms had high accuracy (sensitivity and specificity: 91-99%) but were hampered by uninterpretable recordings (20-24%). In cardiologists' interpretation, the 6-lead device was superior (sensitivity 99%, specificity 97%) to both single-lead smartwatches (P < .05) for atrial fibrillation detection.


Subject(s)
Atrial Fibrillation , Algorithms , Atrial Fibrillation/diagnosis , Electric Countershock , Electrocardiography , Humans , Sensitivity and Specificity
3.
Circulation ; 145(5): 321-329, 2022 02.
Article in English | MEDLINE | ID: mdl-34779221

ABSTRACT

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.


Subject(s)
Arrhythmias, Cardiac/therapy , Defibrillators, Implantable/standards , Aged , Arrhythmias, Cardiac/diagnosis , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
4.
Earths Future ; 9(7): e2020EF001882, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34435072

ABSTRACT

This study provides a literature-based comparative assessment of uncertainties and biases in global to world-regional scale assessments of current and future coastal flood risks, considering mean and extreme sea-level hazards, the propagation of these into the floodplain, people and coastal assets exposed, and their vulnerability. Globally, by far the largest bias is introduced by not considering human adaptation, which can lead to an overestimation of coastal flood risk in 2100 by up to factor 1300. But even when considering adaptation, uncertainties in how coastal societies will adapt to sea-level rise dominate with a factor of up to 27 all other uncertainties. Other large uncertainties that have been quantified globally are associated with socio-economic development (factors 2.3-5.8), digital elevation data (factors 1.2-3.8), ice sheet models (factor 1.6-3.8) and greenhouse gas emissions (factors 1.6-2.1). Local uncertainties that stand out but have not been quantified globally, relate to depth-damage functions, defense failure mechanisms, surge and wave heights in areas affected by tropical cyclones (in particular for large return periods), as well as nearshore interactions between mean sea-levels, storm surges, tides and waves. Advancing the state-of-the-art requires analyzing and reporting more comprehensively on underlying uncertainties, including those in data, methods and adaptation scenarios. Epistemic uncertainties in digital elevation, coastal protection levels and depth-damage functions would be best reduced through open community-based efforts, in which many scholars work together in collecting and validating these data.

5.
Europace ; 23(7): 1003-1015, 2021 07 18.
Article in English | MEDLINE | ID: mdl-33822029

ABSTRACT

AIMS: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients. METHODS AND RESULTS: Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55-71), 62% male] agreed that the FibriCheck® app was easy to use (94%). CONCLUSION: Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.


Subject(s)
Atrial Fibrillation , COVID-19 , Mobile Applications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/therapy , Communicable Disease Control , Female , Humans , Male , Middle Aged , Pandemics , Patient Outcome Assessment , SARS-CoV-2
6.
Eur Heart J Digit Health ; 2(3): 363-373, 2021 Sep.
Article in English | MEDLINE | ID: mdl-36713592

ABSTRACT

Aims: Within the TeleCheck-AF project, numerous centres in Europe used on-demand photoplethysmography (PPG) technology to remotely assess heart rate and rhythm in conjunction with teleconsultations. Based on the TeleCheck-AF investigator experiences, we aimed to develop an educational structured stepwise practical guide on how to interpret PPG signals and to introduce typical clinical scenarios how on-demand PPG was used. Methods and results: During an online conference, the structured stepwise practical guide on how to interpret PPG signals was discussed and further refined during an internal review process. We provide the number of respective PPG recordings (FibriCheck®) and number of patients managed within a clinical scenario during the TeleCheck-AF project. To interpret PPG recordings, we introduce a structured stepwise practical guide and provide representative PPG recordings. In the TeleCheck-AF project, 2522 subjects collected 90 616 recordings in total. The majority of these recordings were classified by the PPG algorithm as sinus rhythm (57.6%), followed by AF (23.6%). In 9.7% of recordings, the quality was too low to interpret. The most frequent clinical scenarios where PPG technology was used in the TeleCheck-AF project was a follow-up after AF ablation (1110 patients) followed by heart rate and rhythm assessment around (tele)consultation (966 patients). Conclusion: We introduce a newly developed structured stepwise practical guide on PPG signal interpretation developed based on presented experiences from TeleCheck-AF. The present clinical scenarios for the use of on-demand PPG technology derived from the TeleCheck-AF project will help to implement PPG technology in the management of AF patients.

7.
Nat Commun ; 8: 15697, 2017 06 15.
Article in English | MEDLINE | ID: mdl-28643784

ABSTRACT

Water scarcity is rapidly increasing in many regions. In a novel, multi-model assessment, we examine how human interventions (HI: land use and land cover change, man-made reservoirs and human water use) affected monthly river water availability and water scarcity over the period 1971-2010. Here we show that HI drastically change the critical dimensions of water scarcity, aggravating water scarcity for 8.8% (7.4-16.5%) of the global population but alleviating it for another 8.3% (6.4-15.8%). Positive impacts of HI mostly occur upstream, whereas HI aggravate water scarcity downstream; HI cause water scarcity to travel downstream. Attribution of water scarcity changes to HI components is complex and varies among the hydrological models. Seasonal variation in impacts and dominant HI components is also substantial. A thorough consideration of the spatially and temporally varying interactions among HI components and of uncertainties is therefore crucial for the success of water scarcity adaptation by HI.

8.
Sci Rep ; 6: 38495, 2016 12 09.
Article in English | MEDLINE | ID: mdl-27934888

ABSTRACT

Water scarcity is a rapidly growing concern around the globe, but little is known about how it has developed over time. This study provides a first assessment of continuous sub-national trajectories of blue water consumption, renewable freshwater availability, and water scarcity for the entire 20th century. Water scarcity is analysed using the fundamental concepts of shortage (impacts due to low availability per capita) and stress (impacts due to high consumption relative to availability) which indicate difficulties in satisfying the needs of a population and overuse of resources respectively. While water consumption increased fourfold within the study period, the population under water scarcity increased from 0.24 billion (14% of global population) in the 1900s to 3.8 billion (58%) in the 2000s. Nearly all sub-national trajectories show an increasing trend in water scarcity. The concept of scarcity trajectory archetypes and shapes is introduced to characterize the historical development of water scarcity and suggest measures for alleviating water scarcity and increasing sustainability. Linking the scarcity trajectories to other datasets may help further deepen understanding of how trajectories relate to historical and future drivers, and hence help tackle these evolving challenges.

9.
Neural Plast ; 2016: 4307694, 2016.
Article in English | MEDLINE | ID: mdl-27403345

ABSTRACT

We previously demonstrated that daily, hour-long training sessions significantly improved both locomotor (limb kinematics, gait, and hindlimb flexor-extensor bursting patterns) and nonlocomotor (bladder function and at-level mechanical allodynia) functions following a moderate contusive spinal cord injury. The amount of training needed to achieve this recovery is unknown. Furthermore, whether this recovery is induced primarily by neuronal activity below the lesion or other aspects related to general exercise is unclear. Therefore, the current study objectives were to (1) test the efficacy of 30 minutes of step training for recovery following a clinically relevant contusion injury in male Wistar rats and (2) test the efficacy of training without hindlimb engagement. The results indicate that as little as 30 minutes of step training six days per week enhances overground locomotion in male rats with contusive spinal cord injury but does not alter allodynia or bladder function. Thirty minutes of forelimb-only exercise did not alter locomotion, allodynia, or bladder function, and neither training protocol altered the amount of in-cage activity. Taken together, locomotor improvements were facilitated by hindlimb step training for 30 minutes, but longer durations of training are required to affect nonlocomotor systems.


Subject(s)
Motor Activity/physiology , Physical Conditioning, Animal/methods , Recovery of Function/physiology , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/rehabilitation , Animals , Locomotion/physiology , Male , Rats , Rats, Wistar , Thoracic Vertebrae , Time Factors
10.
Mitig Adapt Strateg Glob Chang ; 20(6): 865-890, 2015.
Article in English | MEDLINE | ID: mdl-30197555

ABSTRACT

Managing flood risk, i.e. both the hazard and the potential consequences, is an important aspect of adapting to global change and has gained much traction in recent decades. As a result, a priori flood risk assessments have become an important part of flood management practices. Many methodologies have been set up, ranging from global risk assessments for the world as a whole, to local assessments for a particular stretch of a river/coast or small town. Most assessment frameworks generally follow a similar approach, but there are also notable differences between assessments at different spatial scales. This review article examines these differences, for instance those related to the methodology, use of assessments and uncertainties. From this review, future research needs are identified in order to improve flood risk assessments at different scales. At global/continental scale, there is a clear need for harmonised information on flood defences to improve assessments. Furthermore, inclusions of indirect economic effects at the macro-/meso-scale would give a better indication of the total effects of catastrophic flooding. At the meso-/micro-scale, there is an urgent need to improve our understanding of the effects of flooding on critical infrastructures, given their importance to society, the economy, emergency management and reconstruction. An overarching theme at all scales is the validation of flood risk assessments, which is often limited. More detailed post-disaster information would allow for improved calibration, validation and thus performance of flood risk models. Lastly, the link between spatial scales also deserves attention, for instance up- or downscaling methodologies.

11.
Sci Total Environ ; 438: 477-89, 2012 Nov 01.
Article in English | MEDLINE | ID: mdl-23032564

ABSTRACT

Reducing food losses and waste is considered to be one of the most promising measures to improve food security in the coming decades. Food losses also affect our use of resources, such as freshwater, cropland, and fertilisers. In this paper we estimate the global food supply losses due to lost and wasted food crops, and the resources used to produce them. We also quantify the potential food supply and resource savings that could be made by reducing food losses and waste. We used publically available global databases to conduct the study at the country level. We found that around one quarter of the produced food supply (614 kcal/cap/day) is lost within the food supply chain (FSC). The production of these lost and wasted food crops accounts for 24% of total freshwater resources used in food crop production (27 m(3)/cap/yr), 23% of total global cropland area (31 × 10(-3)ha/cap/yr), and 23% of total global fertiliser use (4.3 kg/cap/yr). The per capita use of resources for food losses is largest in North Africa & West-Central Asia (freshwater and cropland) and North America & Oceania (fertilisers). The smallest per capita use of resources for food losses is found in Sub-Saharan Africa (freshwater and fertilisers) and in Industrialised Asia (cropland). Relative to total food production, the smallest food supply and resource losses occur in South & Southeast Asia. If the lowest loss and waste percentages achieved in any region in each step of the FSC could be reached globally, food supply losses could be halved. By doing this, there would be enough food for approximately one billion extra people. Reducing the food losses and waste would thus be an important step towards increased food security, and would also increase the efficiency of resource use in food production.


Subject(s)
Agriculture/statistics & numerical data , Fertilizers/statistics & numerical data , Food Supply/statistics & numerical data , Internationality , Waste Products/analysis , Water Supply/statistics & numerical data , Conservation of Natural Resources , Food Supply/methods , Waste Products/adverse effects
12.
Domest Anim Endocrinol ; 33(4): 390-9, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17029675

ABSTRACT

The present research was conducted to model potential mechanisms through which IGFBPs might be affected by a key proinflammatory response initiating cytokine tumor necrosis factor (TNF-)-alpha. Madin-Darby bovine kidney epithelial (MDBK) cells, known to release IGFBPs in response to several stimuli, were grown under several conditions and challenged with forskolin (F) or recombinant TNF-alpha for 24h. Forskolin increased IGFBP-3 gene expression and media content of BP-3 protein. TNF-alpha increased basal and augmented F-mediated IGFBP-3 gene expression. However, TNF-alpha effects on the measurable media content of IGFBPs were influenced by culture conditions; in the absence of added protease inhibitors (PIs) or sufficient media albumin concentration (high BSA, 1mg/ml), the effect of TNF-alpha was to decrease (P<0.02) measurable IGFBPs. In the presence of PI and high BSA, media IGFBP-3 levels were shown to be increased by TNF-alpha consistent with the gene expression data. Changes in media IGFBP-3 protease activity were examined further to explain the observed effects of TNF-alpha on production and destruction of IGFBPs in media. When recombinant human IGFBP-3 (500 ng/ml) was added to PI-free, low BSA 100 microg/ml) media from TNF-treated MDBK cells, less than 10% of the BP-3 was recognizable by Western blot in 30 min; conversely, inclusion of High BSA and PI in media resulted in attenuation of the protease effect on the IGFBPs. The data suggest that the MDBK model of cellular response to proinflammatory stimulus is affected by culture conditions and that TNF-alpha affects media content of IGFBPs through effects on IGFBP gene expression coupled with degradation of IGFBPs via enhanced proteolytic enzyme release.


Subject(s)
Insulin-Like Growth Factor Binding Proteins/metabolism , Kidney/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Animals , Cattle , Cell Line , Gene Expression/drug effects , Humans , Insulin-Like Growth Factor Binding Protein 2/genetics , Insulin-Like Growth Factor Binding Protein 3/genetics , Insulin-Like Growth Factor Binding Proteins/genetics , Kidney/drug effects , Recombinant Proteins
13.
J Gastroenterol Hepatol ; 16(6): 599-606, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11422610

ABSTRACT

BACKGROUND AND AIMS: Hepatic steatosis has been shown to be associated with lipid peroxidation and hepatic fibrosis in a variety of liver diseases including non-alcoholic fatty liver disease. However, the lobular distribution of lipid peroxidation associated with hepatic steatosis, and the influence of hepatic iron stores on this are unknown. The aim of this study was to assess the distribution of lipid peroxidation in association with these factors, and the relationship of this to the fibrogenic cascade. METHODS: Liver biopsies from 39 patients with varying degrees of hepatic steatosis were assessed for evidence of lipid peroxidation (malondialdehyde adducts), hepatic iron, inflammation, fibrosis, hepatic stellate cell activation (alpha-smooth muscle actin and TGF-beta expression) and collagen type I synthesis (procollagen alpha1 (I) mRNA). RESULTS: Lipid peroxidation occurred in and adjacent to fat-laden hepatocytes and was maximal in acinar zone 3. Fibrosis was associated with steatosis (P < 0.04), lipid peroxidation (P < 0.05) and hepatic iron stores (P < 0.02). Multivariate logistic regression analysis confirmed the association between steatosis and lipid peroxidation within zone 3 hepatocytes (P < 0.05), while for hepatic iron, lipid peroxidation was seen within sinusoidal cells (P < 0.05), particularly in zone 1 (P < 0.02). Steatosis was also associated with acinar inflammation (P < 0.005). alpha-Smooth muscle actin expression was present in association with both lipid peroxidation and fibrosis. Although the effects of steatosis and iron on lipid peroxidation and fibrosis were additive, there was no evidence of a specific synergistic interaction between them. CONCLUSIONS: These observations support a model where steatosis exerts an effect on fibrosis through lipid peroxidation, particularly in zone 3 hepatocytes.


Subject(s)
Fatty Liver/metabolism , Iron Overload/metabolism , Lipid Peroxidation , Liver Cirrhosis/metabolism , Membrane Proteins , Actins/metabolism , Adult , Fatty Liver/pathology , Female , HLA Antigens/genetics , Hemochromatosis , Hemochromatosis Protein , Hepatocytes , Histocompatibility Antigens Class I/genetics , Humans , Immunohistochemistry , Iron/metabolism , Iron Overload/pathology , Liver Cirrhosis/pathology , Male , Malondialdehyde/metabolism , Middle Aged , Procollagen/metabolism , Transforming Growth Factor beta/metabolism
14.
Dev Dyn ; 219(3): 368-80, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11066093

ABSTRACT

FGF5 is expressed in the mesenchyme and skeletal muscle of developing and adult mouse limbs. However, the function of FGF5 during development of the limb and limb musculature is unknown. To elucidate the inherent participation of FGF5 during limb organogenesis, a retroviral delivery system (RCAS) was used to overexpress human FGF5 throughout developing hind limb of chicken embryos. Misexpression of the soluble growth factor severely inhibited the formation of mature myocytes. Limbs infected with RCAS-FGF5 contained smaller presumptive muscle masses as evidenced by a decrease in MyoD and myosin heavy chain expressing cells. In contrast, ectopic expression of FGF5 significantly stimulated proliferation and expansion of the tenascin-expressing, connective-tissue fibroblast lineage throughout the developing limb. Histological analysis demonstrated that the increase in tenascin immunostaining surrounding the femur, ileum, and pubis in the FGF5 infected limbs corresponded to the fibroblasts forming the stacked-cell perichondrium. Furthermore, pulse labeling experiments with the thymidine analog, BrdU, revealed that the increased size of the perichondrium was attributable to enhanced cell proliferation. These results support a model whereby FGF5 acts as a mitogen to stimulate the proliferation of mesenchymal fibroblasts that contribute to the formation of connective tissues such as the perichondrium, and inhibits the development of differentiated skeletal muscle. These results also contend that FGF5 is a candidate mediator of the exclusive spatial patterning of the hind limb connective tissue and skeletal muscle.


Subject(s)
Connective Tissue/embryology , Fibroblast Growth Factors/physiology , Muscle, Skeletal/embryology , Animals , Animals, Genetically Modified , Cell Division , Chick Embryo , Extremities/embryology , Fibroblast Growth Factor 5 , Fibroblast Growth Factors/genetics , Fibroblasts/cytology , Gene Expression Regulation, Developmental , Humans , In Situ Hybridization , Mice , MyoD Protein/genetics , MyoD Protein/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction
15.
Int J Cancer ; 87(5): 734-40, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10925369

ABSTRACT

Alcohol is a recognized risk factor for upper aerodigestive tract (UAT) cancers, but the mechanism by which alcohol causes cancer remains obscure. Ethanol is oxidized to acetaldehyde (the suspected carcinogenic agent in alcohol) by alcohol dehydrogenases (ADHs) and cytochrome P-4502E1 (CYP2E1), both of which exhibit great inter-individual variability in activity. The hypothesis that these polymorphisms influence susceptibility to alcohol-related cancers remains poorly documented. We investigated whether ADH(3) and CYP2E1 DraI and RsaI genotypes modified the risk of UAT cancers among 121 oral cavity/pharyngeal cancer patients, 129 laryngeal cancer patients, and 172 controls, all French Caucasians. Cancer risks and gene-alcohol interactions were analyzed by unconditional logistic regression, accounting for potential confounders. ADH(3) genotype was not associated with UAT cancer. In contrast, a 2-fold risk of oral cavity/pharyngeal (OR = 2.0, 95% CI 1.0-3.9) and laryngeal (OR = 1.8, 95% CI 1.0-3.5) cancers was observed for carriers of the CYP2E1 DraI C variant allele compared with other individuals. The risk associated with the CYP2E1 RsaI c2 variant allele also increased for oral cavity/pharyngeal cancer (OR = 2.6, 95% CI 1.0-6. 6). The effects of ADH(3) or CYP2E1 genotype and alcohol or tobacco were independent. The highest risk of oral cavity/pharyngeal cancer was observed among the heaviest drinkers (>80 g/day) with the CYP2E1 DraI C allele (OR = 5.8, 95% CI 1.9-18.2) or the CYP2E1 RsaI c2 allele (OR = 7.2, 95% CI 1.4-38.2) compared with lighter drinkers with other genotypes. Our study suggests that CYP2E1 genotype modifies the risk of UAT cancers, but due to the low frequency of CYP2E1 variant alleles, large-scale studies are needed to confirm our findings.


Subject(s)
Alcohol Drinking/adverse effects , Aldehyde Oxidoreductases/genetics , Cytochrome P-450 CYP2E1/genetics , Laryngeal Neoplasms/genetics , Mouth Neoplasms/genetics , Pharyngeal Neoplasms/genetics , Aldehyde Oxidoreductases/metabolism , Case-Control Studies , Cocarcinogenesis , Cytochrome P-450 CYP2E1/metabolism , Female , Genetic Predisposition to Disease , Genotype , Humans , Laryngeal Neoplasms/chemically induced , Laryngeal Neoplasms/enzymology , Male , Middle Aged , Mouth Neoplasms/chemically induced , Mouth Neoplasms/enzymology , Pharyngeal Neoplasms/chemically induced , Pharyngeal Neoplasms/enzymology , Polymorphism, Genetic , Risk Factors , Smoking/adverse effects
17.
Neurosurgery ; 43(6): 1445-8; discussion 1448-9, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9848859

ABSTRACT

OBJECTIVE AND IMPORTANCE: Infundibula (IFs) are funnel-shaped symmetrical enlargements that occur at the origins of cerebral arteries and are apparent on 7 to 25% of otherwise normal angiograms. They are frequently considered as normal anatomic variants of no pathogenic significance. CLINICAL PRESENTATION: We report the case of a ruptured posterior communicating artery aneurysm that had developed at the site of a previously known IF in a 49-year-old hypertensive woman. She had a poor conscious level at admission, with widespread subarachnoid hemorrhage and obstructive hydrocephalus. INTERVENTION: The patient was immediately ventilated, and an external ventricular drain was inserted. The aneurysm was successfully clipped; however, secondary hemorrhage occurred both before and during craniotomy. She developed marked hypernatremia and subsequently died. CONCLUSION: This is the 11th case of IF-to-aneurysm progression reported. It suggests that in certain cases, serial investigations may be indicated with IFs to detect aneurysm formation and preempt rupture.


Subject(s)
Aneurysm, Ruptured/pathology , Cerebral Arteries/pathology , Intracranial Aneurysm/pathology , Carotid Arteries/pathology , Cerebral Arteries/anatomy & histology , Craniotomy , Disease Progression , Drainage , Fatal Outcome , Female , Humans , Hydrocephalus/etiology , Hydrocephalus/surgery , Hypernatremia/etiology , Hypertension/complications , Intracranial Aneurysm/surgery , Middle Aged , Recurrence , Rupture, Spontaneous , Subarachnoid Hemorrhage/etiology
18.
Accid Anal Prev ; 30(4): 455-67, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9666242

ABSTRACT

Nine-hundred and seventy-three police road-accident files describing overtaking accidents were sampled from the headquarters of Nottinghamshire Constabulary, England, for the years 1989-1993. Salient facts were extracted from each case, including the exact manoeuvre involved, the principle explanatory factors, the driver(s) most at fault, and the drivers' ages. Two kinds of reliability measure for case interpretations. indicated high levels of consistency. Two induced exposure measures were used, comparing driver involvement in a given type of overtaking accident with involvement in overtaking accidents in general, and comparing the age profiles of the drivers most at fault with those of the other drivers involved. Ten types of overtaking accident were distinguished, and three are discussed in detail: collision with a right-turning vehicle (the most common injury-accident for overtakers), which tends to occur either because a young driver makes a faulty overtaking decision, or an older driver makes a faulty right turn; head-on collision, which affects all age groups roughly in proportion to exposure; and the 'return-and-lose-control' accident, which is associated particularly with young drivers. The study illustrates the 'structured judgement method' of accident causation research, in which human interpreters are used to ascribe causes and processes to individual cases, but orthodox research techniques are used to standardise procedures, and to assess and ensure reliability.


Subject(s)
Accidents, Traffic , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Decision Making , England , Humans , Middle Aged
20.
J Pediatr Orthop B ; 7(2): 141-3, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9597591

ABSTRACT

A review of magnetic resonance imaging (MRI) performed to exclude the presence of spinal dysraphism in children presenting with lower limb pathology is unrewarding in the absence of abnormal neurology. Over a 5-year period, 29 children ages 2 weeks to 15 years with a mean age of 6 years presenting with lower limb abnormalities were referred for MRI of the spine to exclude an occult neurologic cause for the deformities. More than one limb abnormality, for example pes cavus and limb length discrepancy, was present in 93% of the children, and 11 children had severe or recurrent talipes equinovarus deformity. Only two children (7%), both of whom had abnormal limb neurology, had abnormal MRI scans. In the absence of a demonstrable neurologic deficit in the lower limb, there appears to be no advantage in requesting MRI of the spine in children presenting with lower limb abnormality.


Subject(s)
Musculoskeletal Diseases/complications , Spinal Dysraphism/diagnosis , Child , Child, Preschool , Clubfoot/complications , Female , Humans , Infant , Leg , Leg Length Inequality/complications , Magnetic Resonance Imaging , Male , Retrospective Studies
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