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Sökning: WFRF:(Hirsch Jan)

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1.
  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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2.
  • Alimena, Juliette, et al. (författare)
  • Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
  • 2020
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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4.
  • Berg, Lotta, et al. (författare)
  • Yttrande från SLUs vetenskapliga råd för djurskydd om hållande av hund och katt
  • 2018
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Detta yttrande är skrivet på uppdrag av Jordbruksverket i samband med verkets översyn av föreskrifterna för hund och katt. För att Jordbruksverkets föreskrifter ska vara väl förankrade i den senaste forskningen önskar verket inhämta underlag från det vetenskapliga rådet för djurskydd vid Sveriges lantbruksuniversitet, specifikt gällande områdena rörelsebehov, social kontakt och avvänjning.
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5.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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6.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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7.
  • Plejert, Charlotta, 1973- (författare)
  • To fix what’s not broken : repair strategies in non-native and native english conversation
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The thesis investigates conversations involving native speakers and non-nativespeakers of English. The non-native speakers partaking in the study have a welldeveloped knowledge of the foreign language. The study is particularly concernedwith the function and interactional relevance of repair strategies that interlocutorsemploy when they talk to each other. The results of the analyses highlight issuessuch as participants’ self-representations as competent speakers, the notion “nonnativeness”,and language learning, relating to current developments within conversationanalytic research on second/foreign language conversations. Comparisonsbetween non-native and native speakers are made, highlighting similarities as wellas di¡erences in participants’ use of repair strategies.The study adopts a conversation analytic framework but is also in¤uenced bystudies of second/foreign language acquisition. Conversation analytic research has,until recently, dealt with conversations involving non-native speakers who have alimited or intermediate command of the second/foreign language. Repair behavioursof advanced foreign language users are thus a little investigated area. Whereasnon-native speakers with limited experience in using the second/foreign languageoften employ repair in order to solve problems that are related to their linguisticknowledge, such as ¢nding or knowing words and constructing utterances that areunderstandable in the context in which they occur, this thesis shows how an increasedknowledge of the foreign language involves a shift in focus as repair is carriedout, i.e. repair is used to address problems of a linguistic as well as of a socialnature. Since an increased knowledge of a foreign language is accompanied by an increasein the range of jobs that repair strategies do, “doing repair” is an importantpart of the development of non-native speakers’ interactional and linguistic competence.
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8.
  • Bengtsson, Ewert, 1948-, et al. (författare)
  • Detection of Malignancy-Associated Changes Due to Precancerous and Oral Cancer Lesions: A Pilot Study Using Deep Learning
  • 2018
  • Ingår i: CYTO2018.
  • Konferensbidrag (refereegranskat)abstract
    • Background: The incidence of oral cancer is increasing and it is effecting younger individuals. PAP smear-based screening, visual, and automated, have been used for decades, to successfully decrease the incidence of cervical cancer. Can similar methods be used for oral cancer screening? We have carried out a pilot study using neural networks for classifying cells, both from cervical cancer and oral cancer patients. The results which were reported from a technical point of view at the 2017 IEEE International Conference on Computer Vision Workshop (ICCVW), were particularly interesting for the oral cancer cases, and we are currently collecting and analyzing samples from more patients. Methods: Samples were collected with a brush in the oral cavity and smeared on glass slides, stained, and prepared, according to standard PAP procedures. Images from the slides were digitized with a 0.35 micron pixel size, using focus stacks with 15 levels 0.4 micron apart. Between 245 and 2,123 cell nuclei were manually selected for analysis for each of 14 datasets, usually 2 datasets for each of the 6 cases, in total around 15,000 cells. A small region was cropped around each nucleus, and the best 2 adjacent focus layers in each direction were automatically found, thus creating images of 100x100x5 pixels. Nuclei were chosen with an aim to select well preserved free-lying cells, with no effort to specifically select diagnostic cells. We therefore had no ground truth on the cellular level, only on the patient level. Subsets of these images were used for training 2 sets of neural networks, created according to the ResNet and VGG architectures described in literature, to distinguish between cells from healthy persons, and those with precancerous lesions. The datasets were augmented through mirroring and 90 degrees rotations. The resulting networks were used to classify subsets of cells from different persons, than those in the training sets. This was repeated for a total of 5 folds. Results: The results were expressed as the percentage of cell nuclei that the neural networks indicated as positive. The percentage of positive cells from healthy persons was in the range 8% to 38%. The percentage of positive cells collected near the lesions was in the range 31% to 96%. The percentages from the healthy side of the oral cavity of patients with lesions ranged 37% to 89%. For each fold, it was possible to find a threshold for the number of positive cells that would correctly classify all patients as normal or positive, even for the samples taken from the healthy side of the oral cavity. The network based on the ResNet architecture showed slightly better performance than the VGG-based one. Conclusion: Our small pilot study indicates that malignancyassociated changes that can be detected by neural networks may exist among cells in the oral cavity of patients with precancerous lesions. We are currently collecting samples from more patients, and will present those results as well, with our poster at CYTO 2018.
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9.
  • Beniczky, Sándor, et al. (författare)
  • Standardized computer-based organized reporting of EEG : SCORE - Second version
  • 2017
  • Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 128:11, s. 2334-2346
  • Tidskriftsartikel (refereegranskat)abstract
    • Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.
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10.
  • Blomqvist, G, et al. (författare)
  • Association between development of lower lip cancer and tobacco habits
  • 1991
  • Ingår i: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 49:10, s. 1044-1047; discussion 1048
  • Tidskriftsartikel (refereegranskat)abstract
    • Tobacco use is considered to increase the risk of tumor induction. The purpose of this case-controlled investigation was to assess the association of tobacco habits and development of squamous cell carcinoma of the lower lip. Sixty-one patients treated for lower lip cancer, aged between 42 and 90 years, were studied. Age- and sex-matched healthy controls showed a similar exposure to tobacco in years and a comparable distribution of tobacco habits. Although the mean exposure factor (duration times exposure) was greater in the tumor group, no intimate correlation between lip cancer and tobacco was demonstrated. However, an increased, although small, occurrence of herpes labialis lesions was found in cancer patients. The hypothesis is presented that smokers experiencing recurrent herpes simplex virus 1 (HSV-1) infections are more liable to tumor initiation, which issue will be subjected to a future study.
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11.
  • Blomstrand, Lena, et al. (författare)
  • Telemedicine : a complement to traditional referrals in oral medicine
  • 2012
  • Ingår i: Telemedicine journal and e-health. - : Mary Ann Liebert Inc. - 1530-5627 .- 1556-3669. ; 18:7, s. 549-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction:Introducing telemedicine into clinical practice has not been without difficulties. Within the framework of the European Union project "Health Optimum," telemedicine consultations with specialists at the Department of Oral & Maxillofacial Surgery at Uppsala University Hospital (Uppsala, Sweden) have been offered to dentists in the public dental health service. The aim is to streamline the consultation process, improve/develop the skills of the participating dentists and dental hygienists, and save time and money for patients, healthcare authorities, and society.Subjects and Methods:Patient records are collected in a database for demonstration and discussion, and the system is also available for referrals. Both medical and dental photographs and x-rays are digitized in the same system. These can be viewed during telemedicine rounds and by the consultants at the hospital prior to a consultation. Secure, interactive conferencing software is used, which provides a quick, easy, and effective way to share video and data over the Internet. Both parties can demonstrate different parts of an image using a pointer or a drawing system. Conference phones are presently used for verbal communication.Results:Ten patients were discussed during telemedicine rounds (3 males and 7 females), all of whom would normally have been referred to a specialist. As a result of the telemedicine round, 2 were referred to a specialist, whereas diagnoses were made for the other 8, and treatment was suggested. The dental health clinic could thus provide treatment without the need for referral to a consultant.Conclusions:The telemedicine system described here allows patient care to be provided rapidly and more economically. Future plans include "live" rounds using a videocamera, providing the possibility to relay real-time information about the intraoral situation. A camera is being developed and should preferably be permanently installed chair side.
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  • Buitrago-Téllez, C. H., et al. (författare)
  • A comprehensive classification of mandibular fractures : a preliminary agreement validation study
  • 2008
  • Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0901-5027 .- 1399-0020. ; 37:12, s. 1080-8
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluates a comprehensive classification system for mandibular fractures based on imaging analysis. The AO/ASIF scheme, defining three fracture types (A, B, C), three groups within each type (e.g. A1, A2, A3) and three subgroups within each group (e.g. A1.1, A1.2, A1.3) with increasing severity from A1.1 (lowest) to C3.3 (highest) was used. The mandible is divided into two vertical units (I and V), two lateral horizontal units (II and IV) and one central unit (III) comprising the symphyseal and parasymphyseal region. Type A fractures are non-displaced, type B are displaced and type C are multifragmentary/defect injuries. Groups and subgroups are further defined in the classification system. Two classification sessions using semi-automatic software with 7 and 9 surgeons were performed to evaluate 100 fracture cases in the first session and 50 in the second. Inter-observer reliability and individual rater's accuracy were evaluated by kappa coefficient and latent class analysis, respectively. The analysis of inter-observer agreement for the detailed coding showed kappa coefficients around 0.50 with higher agreement among raters in the vertical units. This system allows standardization of documentation of mandibular fractures, although improvement in the definition of categories and their application is required.
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16.
  • Bächli, Heidi, et al. (författare)
  • Skull base and maxillofacial fractures : two centre study with correlation of clinical findings with a comprehensive craniofacial classification system
  • 2009
  • Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 37:6, s. 305-11
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: A comprehensive classification based on high resolution computed tomography (CT) of the whole craniofacial region was correlated with clinical findings of combined skull base and maxillofacial fractures. MATERIAL AND METHODS: In a study of two clinical centres, 70 patients with such injuries were admitted at the Universities of Basel (n=29) and Uppsala (n=41). Clinical signs (rhinorrhoea, periorbital haematoma and pneumencephalus) and surgical versus conservative treatment were correlated with a cranio-maxillofacial injury severity score (CMF-ISS) calculated from the classification system. Fracture classifications were decided in consensus on the basis of CT and semiautomatic classification software. The classification system defined 3 fracture types (A, B, C), 3 groups (A1, A2, A3), and 3 subgroups (A1.1, A1.2, A1.3) with increasing severity from A1.1 (lowest) to C3.3 (highest). RESULTS: Of 70 patients, 43 were operated upon and 27 conservatively treated. The operated patients had significantly higher severity scores than non-operated. Patients with or without periorbital haematoma do not differ significantly in the severity score. The severity of the CMF-ISS score was significantly associated (two sample T-test P<0.01) with the occurrence of pneumencephalus, rhinorrhoea and treatment approach. CONCLUSION: Based on our present results, this system seems to be clinical useful for operative decisions and interventions.
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17.
  • Cesaro, Simone, et al. (författare)
  • Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study
  • 2009
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 49:2, s. 233-240
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. Methods. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. Results. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (Pp. 01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P < .001 and P = .001, respectively). Conclusions. Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.
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  • Damman, Peter, et al. (författare)
  • Long-Term Cardiovascular Mortality after Procedure-Related or Spontaneous Myocardial Infarction in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome : A Collaborative Analysis of Individual Patient Data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)
  • 2012
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 125:4, s. 568-576
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient-pooled dataset of the FRISC-II, ICTUS and RITA-3 (FIR) NSTE-ACS trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated with the Kaplan-Meier method, hazard ratios (HR) were calculated with time-dependent Cox proportional-hazards models. Adjustments were made for the variables associated with long-term outcomes. Of the 5467 patients, 212 endured a procedure-related MI within 6 months after enrolment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who endured a procedure-related MI and comparable to patients without a procedure-related MI (HR 0.66, 95%CI: 0.36-1.20, P=0.17). In patients who endured a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2% and higher than patients without a spontaneous MI (HR 4.52, 95%CI: 3.37-6.06, P<0.001). These HRs did not materially alter after risk adjustments. CONCLUSIONS: Five-year follow-up of NSTE-ACS patients from the three FIR trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast there was a substantially raised long-term mortality after a spontaneous MI.
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20.
  • Damman, Peter, et al. (författare)
  • Timing of Angiography With a Routine Invasive Strategy and Long-Term Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome : A Collaborative Analysis of Individual Patient Data From the FRISC II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) Trials
  • 2012
  • Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 5:2, s. 191-199
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: This study sought to investigate long-term outcomes after early or delayed angiography in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS) undergoing a routine invasive management. Background The optimal timing of angiography in patients with nSTE-ACS is currently a topic for debate.Methods: Long-term follow-up after early (within 2 days) angiography versus delayed (within 3 to 5 days) angiography was investigated in the FRISC-II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) (FIR) nSTE-ACS patient-pooled database. The main outcome was cardiovascular death or myocardial infarction up to 5-year follow-up. Hazard ratios (HR) were calculated with Cox regression models. Adjustments were made for the FIR risk score, study, and the propensity of receiving early angiography using inverse probability weighting.Results: Of 2,721 patients originally randomized to the routine invasive arm, consisting of routine angiography and subsequent revascularization if suitable, 975 underwent early angiography and 1,141 delayed angiography. No difference was observed in 5-year cardiovascular death or myocardial infarction in unadjusted (HR: 1.06, 95% confidence interval [CI]: 0.79 to 1.42, p = 0.61) and adjusted (HR: 0.93, 95% CI: 0.75 to 1.16, p = 0.54) Cox regression models.Conclusions: In the FIR database of patients presenting with nSTE-ACS, the timing of angiography was not related to long-term cardiovascular mortality or myocardial infarction. (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes [ICTUS]; ISRCTN82153174. Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction [the Third Randomised Intervention Treatment of Angina Trials (RITA-3)]; ISRCTN07752711)
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21.
  • Damman, Peter, et al. (författare)
  • Usefulness of the Admission Electrocardiogram to Predict Long-Term Outcomes After Non-ST-Elevation Acute Coronary Syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials)
  • 2012
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 109:1, s. 6-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.
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22.
  • Dérand, Per, et al. (författare)
  • Imaging, virtual planning, design and production of patient specific implants and clinical validation in cranio-maxillo-facial surgery
  • 2012
  • Ingår i: Cranial maxillofacial Trauma and Reconstruction. - : SAGE Publications. - 1943-3875 .- 1943-3883. ; 5:3, s. 137-144
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes®, Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and mesh to replace resected bone that can function as a carrier for bone or bone substitutes were designed and tested during reconstructive maxillofacial surgery. A clinically fit, well within the requirements for what is needed and obtained using traditional free hand bending of commercially available devices, or even higher precision, was demonstrated in ablative surgery in four patients.
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23.
  • Dérand, Per, et al. (författare)
  • Virtual bending of mandibular reconstruction plates using a computer-aided design
  • 2009
  • Ingår i: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 67:8, s. 1640-1643
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The purpose of this study was to investigate the possibility of virtually designing and manufacturing a template for reconstruction plate bending, to be used during treatment of congenital or acquired bony entities. The outcome was compared with plates bent by the freehand approach in a stereolithographic skull model. MATERIALS AND METHODS: From a computed tomography examination, a polygon skull was created and the corresponding stereolithographic model retrieved. A polygon mesh of a Compact UniLock 2.4-mm plate was obtained from Synthes (Bettlach, Switzerland). The polygon plate was bent virtually around the mandible and rendered in all 3 dimensions, and a template was created. Five 10-hole plates were bent using this template, and five 10-hole plates were bent using a stereolithographic model as the template. The 2 groups were compared using the Wilcoxon signed rank test. P values less than .001 was considered to be statistically significant. RESULTS: No statistical difference was seen between the 2 methods. The median discrepancy between the 2 groups was 0.1 mm. CONCLUSION: Within the constraints of this investigation, by use of a virtually produced template based on a virtually planned reconstruction, it is possible to bend a reconstruction plate with the same degree of accuracy as that of the traditional freehand approach.
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24.
  • Edman, Kristina, 1958-, et al. (författare)
  • Dental hygienists and dentists as providers of brush biopsies for oral mucosa screening
  • 2023
  • Ingår i: International Journal of Dental Hygiene. - : John Wiley & Sons. - 1601-5029 .- 1601-5037. ; 21:3, s. 524-532
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundOral cancer is a severe and potentially fatal disease usually starting in the squamous epithelium lining the oral cavity. Together with oropharyngeal carcinoma, it is the fifth to sixth most common malignancy worldwide. To limit the increase in the global oral cancer incidence over the past two decades, the World Health Assembly adopted a resolution urging member states to integrate preventive measures such as engagement and training of dental personnel in screening, early diagnosis, and treatment into their national cancer control programs.AimThe aim of this study was to investigate if dental hygienists (DHs) and dentists (Ds) in general dental practice care can be entrusted to perform brush sampling of oral potentially malignant disorders (OPMDs), and to evaluate their level of comfort in performing brush biopsies.MethodsParticipants were five DHs and five Ds who received one day of theoretical and clinical training in oral pathology to identify OPMDs (leukoplakia [LP], erythroplakia [EP], and oral lichen planus [OLP]), and perform brush sampling for PAP cytology and high-risk human papillomavirus (hrHPV) analysis.ResultsOut of 222 collected samples, 215 were adequate for morphological assessment and hrHPV analysis. All the participants agreed that sample collection can be incorporated in DHs and Ds routine clinical duties, and most of them reported that sample collection and processing was easy/quite easy.ConclusionDentists and DHs are capable of collecting satisfactory material for cytology and hrHPV analysis. All the participating DHs and Ds were of the opinion that brush sampling could be handled routinely by DHs and Ds in GDP.
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25.
  • Ekstrand, Karl, et al. (författare)
  • Malignant tumors of the maxilla : virtual planning and real-time rehabilitation with custom-made R-zygoma fixtures and carbon-graphite fiber-reinforced polymer prosthesis
  • 2008
  • Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 10:1, s. 23-29
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oral cancer is a mutilating disease. Because of the expanding application of computer technology in medicine, new methods are constantly evolving. This project leads into a new technology in maxillofacial reconstructive therapy using a redesigned zygoma fixture. PURPOSE: Previous development experiences showed that the procedure was time-consuming and painful for the patients. Frequent episodes of sedation or general anesthetics were required and the rehabilitation is costly. The aim of our new treatment goal was to allow the patients to wake up after tumor surgery with a functional rehabilitation in place. MATERIALS AND METHODS: Stereolithographic models were introduced to produce a model from the three-dimensional computed tomography (CT). A guide with the proposed resection was fabricated, and the real-time maxillectomy was performed. From the postoperative CT, a second stereolithographic model was manufactured and in addition, a stent for the optimal position of the implants. Customized zygoma implants were installed (R-zygoma, Integration AB, Göteborg, Sweden). A fixed construction was fabricated by using a new material based on poly(methylacrylate) reinforced with carbon/graphite fibers and attached to the implants. On the same master cast, a separate obturator was fabricated in permanent soft silicon. RESULTS: The result of this project showed that it was possible to create a virtual plan preoperatively to apply during surgery in order for the patient to wake up functionally rehabilitated. CONCLUSION: From a quality-of-life perspective, it is an advantage to be rehabilitated fast. By using new computer technology, pain and discomfort are less and the total rehabilitation is faster, which in turn reduces days in hospital and thereby total costs.
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26.
  • Eliasson, Alf, 1959, et al. (författare)
  • A 5-year prospective clinical study of submerged and nonsubmerged Paragon system implants in the edentulous mandible.
  • 2010
  • Ingår i: The International journal of prosthodontics. - : Quintessence. - 0893-2174 .- 1139-9791. ; 23:3, s. 231-8
  • Forskningsöversikt (refereegranskat)abstract
    • PURPOSE: The aim of this investigation was to evaluate the clinical outcome of two different surgical protocols in the edentulous mandible: submerged and nonsubmerged. Further, the Paragon dental implant with a titanium plasma-sprayed surface was evaluated. MATERIALS AND METHODS: Twenty-nine consecutively treated patients with 168 implants supporting fixed prostheses were included. All but 3 patients were provided 6 implants, placed via nonsubmerged healing on one side and submerged healing on the other. Data were collected from patient records and radiographs. Twenty-four patients participated in the 5-year clinical follow-up examination. RESULTS: After 5 years, all patients still had their mandibular fixed prostheses in function. Cumulative survival rates were 100% for prostheses and 99.4% for implants. However, 3 implants fractured in 1 patient. One submerged implant was lost before loading but no further implants were lost during follow-up. The radiographic bone loss was small for all implants with a mean of 0.14 mm (standard deviation [SD]: 0.37) at 1 year and 0.42 mm (SD: 0.48) at 5 years for nonsubmerged implants and 0.17 mm (SD: 0.32) at 1 year and 0.51 mm (SD: 0.33) at 5 years for submerged implants. Nineteen implants (including the 3 that fractured) presented annual bone loss exceeding 0.2 mm after the first year, yielding a cumulative success rate of 86.2% after 5 years. CONCLUSION: Single-stage surgery was shown to have the same predictability as two-stage surgery in the anterior edentulous mandible. Paragon implants with a titanium plasma-sprayed surface showed a fracture rate of 2.2% and a success rate of 86.2% after 5 years.
  •  
27.
  •  
28.
  • Esposito, M, et al. (författare)
  • Biological factors contributing to failures of osseointegrated oral implants. (I) : Success criteria and epidemiology
  • 1998
  • Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 106:1, s. 527-551
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this review was to offer a critical evaluation of the literature and to provide the clinician with scientifically-based diagnostic criteria for monitoring the implant condition. The review presents the current opinions on definitions of osseointegration and implant failure. Further, distinctions between failed and failing implants are discussed together with the presently used parameters to assess the implant status. Radiographic examinations together with implant mobility tests seem to be the most reliable parameters in the assessment of the prognosis for osseointegrated implants. On the basis of 73 published articles, the rates of early and late failures of Brånemark implants, used in various anatomical locations and clinical situations, were analyzed using a metanalytic approach. Biologically related implant failures calculated on a sample of 2,812 implants were relatively rare: 7.7% over a 5-year period (bone graft excluded). The predictability of implant treatment was remarkable, particularly for partially edentulous patients, who showed failure rates about half those of totally edentulous subjects. Our analysis also confirmed (for both early and late failures) the general trend of maxillas, having almost 3 times more implant losses than mandibles, with the exception of the partially edentulous situation which displayed similar failure rates both in upper and lower jaws. Surgical trauma together with anatomical conditions are believed to be the most important etiological factors for early implant losses (3.60% of 16,935 implants). The low prevalence of failures attributable to peri-implantitis found in the literature together with the fact that, in general, partially edentulous patients have less resorbed jaws, speak in favour of jaw volume, bone quality, and overload as the three major determinants for late implant failures in the Brånemark system. Conversely, the ITI system seemed to be characterized by a higher prevalence of losses due to peri-implantitis. These differences may be attributed to the different implant designs and surface characteristics. On the basis of the published literature, there appears to be a number of scientific issues which are yet not fully understood. Therefore, it is concluded that further clinical follow-up and retrieval studies are required in order to achieve a better understanding of the mechanisms for failure of osseointegrated implants.
  •  
29.
  • Esposito, M, et al. (författare)
  • Biological factors contributing to failures of osseointegrated oralimplants. (II) : Etiopathogenesis
  • 1998
  • Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 106:3, s. 721-764
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present review is to evaluate the English language literature regarding factors associated with the loss of oral implants. An evidence-based format in conjunction, when possible, with a meta-analytic approach is used. The review identifies the following factors to be associated with biological failures of oral implants: medical status of the patient, smoking, bone quality, bone grafting, irradiation therapy, parafunctions, operator experience, degree of surgical trauma, bacterial contamination, lack of preoperative antibiotics, immediate loading, nonsubmerged procedure, number of implants supporting a prosthesis, implant surface characteristics and design. Excessive surgical trauma together with an impaired healing ability, premature loading and infection are likely to be the most common causes of early implant losses. Whereas progressive chronic marginal infection (peri-implantitis) and overload in conjunction with the host characteristics are the major etiological agents causing late failures. Furthermore, it appears that implant surface properties (roughness and type of coating) may influence the failure pattern. Various surface properties may therefore be indicated for different anatomical and host conditions. Finally, the histopathology of implant losses is described and discussed in relation to the clinical findings.
  •  
30.
  • Esposito, Marco, et al. (författare)
  • Differential diagnosis and treatment strategies for biologic complications and failing oral implants : a review of the literature
  • 1999
  • Ingår i: International Journal of Oral & Maxillofacial Implants. - 0882-2786 .- 1942-4434. ; 14:4, s. 473-490
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this article was to review the literature on differential diagnosis and treatment of biologic complications and failing implants. All types of publications, with the exception of abstracts, published in English up to December 1998, were included. A multi-layered search strategy was used. Controlled clinical trials (CCTs) were searched in the Cochrane Oral Health Group's Specialized Register of Trials. This database contains all CCTs identified in MEDLINE and EMBASE. PubMed was searched using various key words and the "related articles" feature. All identified publications were obtained and none were excluded. Infection, impaired healing, and overload are considered the major etiologic factors for the loss of oral implants. Only a few clinical and animal investigations were found that tested the validity of the proposed therapeutic approaches. The treatment of failing implants is still based mainly on empirical considerations, often derived from periodontal research, from data extrapolated from in vitro findings, or from anecdotal case reports performed on a trial-and-error basis.
  •  
31.
  • Esposito, M, et al. (författare)
  • Failure patterns of four osseointegrated oral implant systems
  • 1997
  • Ingår i: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 8:12, s. 843-847
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this metanalysis was to investigate possible differences in failure patterns among four different osseointegrated oral implant systems. Only systems with a supposed scientific validation, based on long-term follow-up studies, were selected for this analysis, i.e. the Brånemark system, the Calcitek Integral system, the Interpore IMZ system and the Straumann ITI system. While several prospective reports could be found on the Brånemark system, only a few retrospective investigations concerning the ITI and the IMZ systems were available. No data on the Integral system could be employed. Despite these limitations, a substantial difference in failure patterns among various implant systems was observed. The Brånemark implants showed a higher incidence of early failures, though sharply decreasing over time. On the contrary, IMZ implant characterized by rougher surfaces displayed a lower incidence of early failures, but showed constant or increased failure rates over time. For the ITI implants, for example, a higher prevalence of late failures, attributable to chronic bacterial infection (peri-implantitis), was observed when compared to the Brånemark system. With the exception of the latter implant system, prospective long-term follow-up studies, using similar and well-defined success criteria, are needed for the others to confirm the current preliminary findings.
  •  
32.
  • Farzad, Payam, et al. (författare)
  • Högteknologi revolutionerar kraniomaxillofacial kirurgi : Datornavigation ger bättre precision och färre komplikationer
  • 2009
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:38, s. 2362-2365
  • Tidskriftsartikel (refereegranskat)abstract
    • Inom kraniofacial kirurgi pågår en högteknologisk utveckling. Datorstödd och datornavigerad kirurgi är områden som i dag utvecklas snabbt. Nyttan med dessa teknologier är framför allt förbättrad precision och förutsägbarhet med minskad risk för komplikationer och totalt mindre morbiditet. Virtuell planering av rekonstruktioner kan nu göras i och med att datortomografin utvecklats från analog till digital teknik. En ideal simulering av det tilltänkta ingreppet görs sedan på en datorarbetsstation. Osteotomier, förflyttningar av bensegment eller inpassning av biomaterial kan simuleras oändligt antal gånger. Med hjälp av individuellt producerade guider i stereolitografi eller med en navigator överförs den virtuella planen till operationssituationen.
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33.
  • Haj-Hosseini, Neda, 1980-, et al. (författare)
  • Early Detection of Oral Potentially Malignant Disorders: A Review on Prospective Screening Methods with Regard to Global Challenges
  • 2024
  • Ingår i: Journal of Maxillofacial & Oral Surgery. - New Delhi, India : Springer Science and Business Media LLC. - 0972-8279 .- 0974-942X. ; 23:1, s. 23-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral cancer is a cancer type that is widely prevalent in low-and middle-income countries with a high mortality rate, and poor quality of life for patients after treatment. Early treatment of cancer increases patient survival, improves quality of life and results in less morbidity and a better prognosis. To reach this goal, early detection of malignancies using technologies that can be used in remote and low resource areas is desirable. Such technologies should be affordable, accurate, and easy to use and interpret. This review surveys different technologies that have the potentials of implementation in primary health and general dental practice, considering global perspectives and with a focus on the population in India, where oral cancer is highly prevalent. The technologies reviewed include both sample-based methods, such as saliva and blood analysis and brush biopsy, and more direct screening of the oral cavity including fluorescence, Raman techniques, and optical coherence tomography. Digitalisation, followed by automated artificial intelligence based analysis, are key elements in facilitating wide access to these technologies, to non-specialist personnel and in rural areas, increasing quality and objectivity of the analysis while simultaneously reducing the labour and need for highly trained specialists.
  •  
34.
  • Hasséus, B., et al. (författare)
  • Immunotoxic effects of smokeless tobacco on the accessory cell function of rat oral epithelium
  • 1997
  • Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 105:1, s. 45-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Smokeless tobacco (ST) is known to adversely effect the oral mucosa, but knowledge about the influence on immune defence is limited. Few studies have investigated the effect of ST on the local immune response. In the present study, we have assessed the effect of a crude Swedish moist snuff (SS) extract, alkaloids, and nitrosamines on T-cell mitogenic response to Con A using epithelial cells, including Langerhans cells, of the rat oral mucosa as accessory cells. SS extract at a concentration of 4% reduced the T-cell proliferation by 50% (IC50 = 4%). Pretreatment of either oral epithelial cells or T-cells with SS extract also gave a significant inhibition of T-cell proliferation. This effect was not obtained following preincubation with SS components as alkaloids and different tobacco-specific nitrosamines (TSNA). None of the tested compounds were found to possess any mitogenic properties. This in vitro study showed that SS extract can evoke an immunosuppressive effect on mitogen-driven T-cell proliferation using cells from oral epithelium as accessory cells. This effect was more pronounced when SS extract was employed compared to when the single SS components were used alone.
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35.
  • Hedner, E, et al. (författare)
  • Primary herpes simplex virus (type 1) infection delays healing of oral excisional and extraction wounds in the rat
  • 1990
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 19:10, s. 471-476
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of acute herpes simplex virus type 1 (HSV-1) infection on the healing process of intraoral wounds and tooth extraction sockets in the rat was studied. A standardized size of the buccal mucosa was excised and molars were extracted and a HSV-1 suspension was topically applied. The virus infected wounds were clinically characterized by erythema and swelling and histologically by heavy inflammation cell infiltrate and abscesses during the first week. The acute HSV-1 infection was found to significantly delay healing of both types of wounds by 3 days. Antiviral treatment with acyclovir (ACV) decreased the degree of inflammation and improved healing of the infected wounds. The present results indicate a delayed and disturbed healing of wounds in the oral cavity in the presence of HSV-1. The findings may have a clinical significance for primary or latent HSV-1 infections in conjunction with surgical intervention in the oral cavity.
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36.
  • Hedner, E, et al. (författare)
  • Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction
  • 1993
  • Ingår i: Journal of oral and maxillofacial surgery (Print). - 0278-2391 .- 1531-5053. ; 51:4, s. 370-376; discussion 377
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was designed to evaluate a possible association between reactivated herpes simplex virus type 1 (HSV-1) infection after lower third molar extraction and development of dry socket (DS). The HSV-1 antibody response was analyzed before and after tooth removal by enzyme-linked immunosorbent assay and immunoblotting in 208 patients. History of previous possible oral herpes reactivation was evaluated by a questionnaire that was based on self-rated frequency of oral cold sores. Tobacco users were identified. The anatomic proximity of the root apex to the mandibular nerve canal was classified radiographically before extraction. Fifteen patients (7%) developed DS after tooth extraction. Eleven of the 15 DS patients (73%) were HSV seropositive as compared with 7 of 15 (47%) in the matched control group. Seven of the 11 seropositive DS patients have shown HSV-1 reactivation by an increase of specific polypeptides, predominantly gB, gC, gD and ICP 4 and 6, in the immunoblot test. No change in HSV-1 reactivity was observed in control sera. DS patients reported a high frequency of oral cold sores (64%) compared with the controls (33%). Tobacco use was not found to influence the frequency of cold sores or the development of DS. A close radiographic proximity between the mandibular canal and root apex was more common (P < .05) in DS patients. The results indicate that extraction of a mandibular third molar could be a possible cause of reactivation and recurrence of an HSV-1 infection. The serum antibody response, the anatomical nerve/root proximity, and the history of oral cold sores reflect an association between HSV-1 and DS after tooth extraction.
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37.
  • Hedner, E, et al. (författare)
  • Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues
  • 1993
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 22:5, s. 214-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Tooth extraction in rats was used to trigger a latent HSV-1 infection. HSV-1 was inoculated unilaterally in the rat palates. Eight weeks later two molars were removed bilaterally. The trigeminal ganglia were co-cultivated and HSV-1 was isolated from 63% of the ganglia on the infected sides but from only 11% on control sides. The immune response pattern was analysed by immunoblotting of rat serum, and strong reactivity to HSV-1 specific cell polypeptides and glycoproteins (ICP6, gC, pgC, gD) was seen after reactivation. The extraction sockets were histopathologically evaluated and showed healing on the infected side in 26% compared to 63% in contralateral control sockets. The effect of acyclovir (ACV) treatment was elucidated and was found to influence the subsequent development of antibodies and to promote healing of the sockets. Vesiculation in intra- and subepithelial tissue was present on the infected side in 58% but in only 12% of ACV-treated animals. The present study in rats has shown that a latent HSV-1 infection can be established and reactivated by tooth extraction. Reactivation resulted in delayed healing of sockets on the latently infected side but not on the contralateral control side. HSV-1 reactivation was demonstrated serologically by immunoblotting. Healing was significantly promoted by administration of ACV, which also supports the contention that HSV-1 interferes with the healing process.
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38.
  • Hillbertz, Nicolette Salmon, et al. (författare)
  • Viral and Molecular Aspects of Oral Cancer
  • 2012
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:10, s. 4201-4212
  • Forskningsöversikt (refereegranskat)abstract
    • Squamous cell carcinoma (SCC) is the most common epithelial malignancy in the oral cavity. SCCs and their variants constitute over 90% of oral malignancies, and the disease is associated with poor prognosis. OSCC is a complex malignancy where environmental factors, virus infections, and genetic alterations most likely interact, and thus give rise to the malignant condition. Herein, we review the available literature regarding high-risk factors such as alcohol and tobacco usage; discuss the roles of human papillomaviruses (HPV), the Epstein-Barr virus, and the human herpes simplex virus (HSV); and evaluate several candidate genes associated with the condition: p53, p16(INK4) and p21(WAF1/CIP1) survivin, B-cell lymphoma-2 (BCL-2), keratins, Fibroblast growth factor 3 (FGF3), FGF4, FGF19, Oral cancer overexpressed gene 1 (ORAOV1), and Cyclin D1 (CCND1).
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39.
  • Hirsch, Jan, et al. (författare)
  • A paradigm shift in the prevention and diagnosis of oral squamous cell carcinoma
  • 2023
  • Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 52:9, s. 826-833
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Oral squamous cell carcinoma (OSCC) is a widespread disease with only 50%-60% 5-year survival. Individuals with potentially malignant precursor lesions are at high risk.Methods: Survival could be increased by effective, affordable, and simple screening methods, along with a shift from incisional tissue biopsies to non-invasive brush biopsies for cytology diagnosis, which are easy to perform in primary care. Along with the explainable, fast, and objective artificial intelligence characterisation of cells through deep learning, an easy-to-use, rapid, and cost-effective methodology for finding high-risk lesions is achievable. The collection of cytology samples offers the further opportunity of explorative genomic analysis.Results: Our prospective multicentre study of patients with leukoplakia yields a vast number of oral keratinocytes. In addition to cytopathological analysis, whole-slide imaging and the training of deep neural networks, samples are analysed according to a single-cell RNA sequencing protocol, enabling mapping of the entire keratinocyte transcriptome. Mapping the changes in the genetic profile, based on mRNA expression, facilitates the identification of biomarkers that predict cancer transformation.Conclusion: This position paper highlights non-invasive methods for identifying patients with oral mucosal lesions at risk of malignant transformation. Reliable non-invasive methods for screening at-risk individuals bring the early diagnosis of OSCC within reach. The use of biomarkers to decide on a targeted therapy is most likely to improve the outcome. With the large-scale collection of samples following patients over time, combined with genomic analysis and modern machine-learning-based approaches for finding patterns in data, this path holds great promise.
  •  
40.
  •  
41.
  • Hirsch, Jan-Mikael, et al. (författare)
  • A clinical evaluation of the Zygoma fixture: one year of follow-up at 16 clinics.
  • 2004
  • Ingår i: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 62:9 Suppl 2, s. 22-9
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To evaluate treatment outcome with Zygoma fixtures (Nobel Biocare, Göteborg, Sweden) with regard to fixture survival, patient satisfaction, and function of prosthesis replacement. MATERIALS AND METHODS: The treatment outcome of 76 patients treated with 145 Zygoma fixtures at 16 centers was evaluated. Patient's and dentist's evaluations of the functional and aesthetic outcome of the treatment were assessed at delivery of prosthesis and at the 1-year follow-up visit. At the 1-year follow-up visit, the status of the peri-implant mucosa around the abutments and the amount of plaque were registered. RESULTS: Sixty-six of the 76 patients, with 124 Zygoma fixtures supporting the prosthetic restorations, were evaluated at the 1-year follow-up. The overall survival rate for the Zygoma fixtures was 97.9% after 1-year of follow-up. Eighty percent of the patients were fully satisfied with both aesthetic and functional outcome at the time of prosthetic insertion and at the 1-year follow-up. All reported data from the dentists, with the exception of one restoration with several abutment screw loosenings, scored from acceptable to excellent for the aesthetic and functional outcome of the treatment. The status of peri-implant mucosa was recorded as normal in approximately 60% of the sites. Plaque, when present, was more often detected on the palatal surfaces compared with the buccal surfaces. CONCLUSION: This 1-year follow-up of Zygoma fixtures has shown good results with an acceptable number of minor complications and a majority of satisfied patients.
  •  
42.
  • Hirsch, Jan M, et al. (författare)
  • A clinical, histomorphological and histochemical study on snuff-induced lesions of varying severity
  • 1982
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 11:5, s. 387-398
  • Tidskriftsartikel (refereegranskat)abstract
    • The oral lesions in 50 habitual snuff-dippers were graded on a four-point scale. The patients' tobacco and drinking habits were studied by means of a questionnaire. From each patient a biopsy was taken for histomorphological and histochemical analysis. A correlation between snuff habits and the clinical degrees was found, as well as between the snuff habits and certain superficial and deeply located cell changes. The incidence of keratinized lesions, sialadenitis and slight dysplasia (based on subjective evaluation under a light microscope) was higher than previously reported. Presence of dysplastic changes could not be predicted by means of the parameters which characterise the snuff habit or from the clinical grade. The histomorphological and histochemical results were interpreted as showing that the mucosa react to snuff inducing hyperplasia in the basal cell layers. In the surface layer indications of lethal damage were found. The overall stromal reaction to snuff was weak. However, the salivary glands and excretory ducts exhibited degenerative changes which were found to be more severe than the pathological changes in the surface epithelium.
  •  
43.
  • Hirsch, Jan M, et al. (författare)
  • Effect of long-term application of snuff on the oral mucosa : an experimental study in the rat
  • 1983
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 12:3, s. 187-198
  • Tidskriftsartikel (refereegranskat)abstract
    • The long-term effect of snuff exposure was studied in Sprague-Dawley rats using a surgically-created test canal in the lower lip to retain snuff. The rats received standard snuff (n = 42) and highly alkaline snuff (n = 10) for 9-22 months, whereupon they were killed. Untreated rats with identical test canals (n = 15) served as controls. A complete post-mortem examination was performed. One rat exposed to standard snuff for 9 months developed a squamous cell carcinoma of the oral cavity. However, exposure to standard snuff usually resulted in a mild to moderate hyperplasia of the epithelium, hyperorthokeratosis and acanthosis. Rats exposed to snuff for 18-22 months showed vacuolated cells penetrating deeper into the epithelium with hyperplastic and atrophic lesions. In a few rats, severe dysplastic changes developed in the crevicular epithelium. Rats exposed to alkaline snuff differed little from the first group except that there was focally atrophic and ulcerated epithelium and less fibrosis. Pathological findings outside the oral cavity were rare. Squamous cell hyperplasia of the forestomach was found in rats exposed to snuff for 18-22 months, possibly caused by ingested snuff. In conclusion, this study has shown that exposure of rats to snuff for 10-16 hours per day 5 days a week for most of their life-span resulted in lesions mainly restricted to the epithelium and the underlying connective tissue of the surgically created test canal.
  •  
44.
  • Hirsch, Jan M, et al. (författare)
  • Fixture stability and nerve function after transposition and lateralization of the inferior alveolar nerve and fixture installation
  • 1995
  • Ingår i: British Journal of Oral & Maxillofacial Surgery. - : Elsevier BV. - 0266-4356 .- 1532-1940. ; 33:5, s. 276-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty-four posterior mandibular segments in 18 patients were operated on placing implants after mobilisation of the neurovascular bundle. Two different surgical techniques, transposition and lateralization was used. The overall survival rate of fixtures was 92.1%. Performing lateralization resulted in 100% success, while transposition resulted in 80% stable fixtures in the involved segments. The mean time to full restoration of nerve function was 3.8 weeks after lateralization and 5.7 weeks after tranposing the nerve. Three patients exhibited persisting slight hyposthesia, but all, subjectively negligible disturbances in nerve function.
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45.
  • Hirsch, Jan M, et al. (författare)
  • Hemodynamic effects of the use of oral snuff
  • 1992
  • Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 52:4, s. 394-401
  • Tidskriftsartikel (refereegranskat)abstract
    • The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.
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46.
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47.
  • Hirsch, Jan M, et al. (författare)
  • Inhibition of herpes simplex virus replication by tobacco extracts
  • 1984
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 44:5, s. 1991-1997
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex virus type 1 (HSV-1) has been associated with the genesis of leukoplakias, epithelial atypia, and oral cancer. Tobacco habits, such as snuff dipping, are also definitely correlated with this type of lesion. The normal cytolytic HSV-1 infection can, after in vitro inactivation, transform cells. Extracts of snuff were prepared and assayed for their ability to inhibit HSV-1 replication. Plaque formation assays of HSV-1 in the presence of snuff extract showed that a reduced number of plaques was formed. Different batches of one brand of snuff were tested for inhibition of herpes simplex virus (HSV) production. More than 99% inhibition of 24-hr HSV production was obtained with undiluted batches. The 1:5 dilutions of snuff had an inhibitory effect of 85% and 1:25 dilutions, 39%. In agreement, the attachment of the virus to the host cell and penetration of the virus to the cell nuclei were found to be inhibited as was the synthesis of viral DNA. Nicotine had an inhibitory effect, while aromatic additions to snuff were found to have no major inhibitory effect on HSV replication. Snuff extracts were prepared from different brands of snuff reported to contain high and low quantities of tobacco-specific N-nitrosamines. Brands with reported high levels of tobacco-specific N-nitrosamines had significantly greater ability to inhibit HSV replication. In conclusion, this study has shown that extracts of snuff have inhibitory effects on the production of cytolytic HSV-1 infections. A chronic snuff dipper keeps tobacco in the mouth for the major part of the day. Thus, virus shed in the oral cavity in connection with a reactivated latent HSV-1 infection has great possibilities of being affected by snuff or derivatives of snuff. It is suggested that an interaction between tobacco products and HSV-1 might be involved in the development of dysplastic lesions in the oral cavity.
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48.
  • Hirsch, Jan M, et al. (författare)
  • Maxillary sinus augmentation using mandibular bone grafts and simultaneous installation of implants : A surgical technique
  • 1991
  • Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 2:2, s. 91-96
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents a specific technique for maxillary sinus augmentation and simultaneous placement of implants in partially edentulous patients. In such patients, there is from time to time insufficient interarch distance for any type of onlay grafting. Health, non-smoking patients without previous or present sinus pathology, where the radiological and clinical examination revealed insufficient height and/or width of the remaining alveolar process in the posterior maxillary region, were selected. They were operated on using a mandibular bone graft obtained from the symphyseal region between the mental foramina and placed in the maxillary sinus. The recipient site was prepared by cutting in a rectangular shape the lateral sinus wall into the sinus lining. The bone wall was then separated towards the lateral nasal wall by rotating the inferior portion of the cut sinus wall medially. In the space thus created, the bone graft was placed. Fixtures were installed at the same session. The method described has proved to be uncomplicated to perform under local anesthesia and no major disadvantages for the patient or pre- or postoperative complications have so far been observed.
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49.
  • Hirsch, Jan-Michael, et al. (författare)
  • Oral Cancer in Swedish Snuff Dippers
  • 2012
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3327-3330
  • Tidskriftsartikel (refereegranskat)abstract
    • Over recent decades there has been debate over whether or not Swedish snuff is carcinogenic in humans. Animal studies and molecular biological and experimental studies have shown the carcinogenic potential of Swedish snuff, but this has not been proved in prospective randomized studies. We present a case series of patients with oral squamous cell carcinomas diagnosed at the sites where the patients had used Swedish snuff for several years. Sixteen male patients were referred to and treated at Oral and Maxillofacial Surgery Departments and Ear, Nose and Throat clinics at seven different hospitals in Sweden. The mean age of the patients at the time of diagnosis was 72.9 years and the mean time of snuff use prior to cancer diagnosis was 42.9 years. This case series shows that Swedish snuff may not be a harmless alternative to smoking.
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50.
  • Hirsch, Jan M, et al. (författare)
  • Periapical surgery
  • 1979
  • Ingår i: International journal of oral surgery. - 0300-9785. ; 8:3, s. 173-185
  • Tidskriftsartikel (refereegranskat)abstract
    • A retrospective study of 572 teeth treated with periapical surgery was undertaken in order to evaluate the influence of preoperative, operative and postoperative factors in the healing process as well as the operation method used. It was also the aim to assess whether the histophatological diagnosis of biopsies taken at the operation could be correlated to healing. Statistical analyses by the AID method and conventional cross-classification methods were performed. Factors of importance were found to be the extent of the destrucion, the operation method used, the bone surrounding the destruction, the quality of the orthograde root filling, the age of the patient, and the marginal bone buccally. The operation method was of importance in large destructions where root fillings were considered as not having properly sealed the canals, and when treating inflamed cysts. The histopathological diagnosis could not be ascribed any definite prognostic value.
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