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  • 1.
    Bengtsson, Ewert
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control. Uppsala university.
    Wieslander, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Forslid, Gustav
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Wählby, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Runow Stark, Christina
    Kecheril Sadanandan, Sajith
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Detection of Malignancy-Associated Changes Due to Precancerous and Oral Cancer Lesions: A Pilot Study Using Deep Learning2018In: CYTO2018 / [ed] Andrea Cossarizza, 2018Conference paper (Refereed)
    Abstract [en]

    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.

  • 2. Blomqvist, G
    et al.
    Hirsch, Jan M
    Department of Oral Surgery, University of Göteborg, Sweden.
    Alberius, P
    Association between development of lower lip cancer and tobacco habits1991In: Journal of oral and maxillofacial surgery (Print), ISSN 0278-2391, E-ISSN 1531-5053, Vol. 49, no 10, p. 1044-1047; discussion 1048Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Blomstrand, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Gullbrandsson, Lotta
    Eklund, Benny
    Kildal, Morten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Telemedicine: a complement to traditional referrals in oral medicine2012In: Telemedicine journal and e-health, ISSN 1530-5627, E-ISSN 1556-3669, Vol. 18, no 7, p. 549-553Article in journal (Refereed)
    Abstract [en]

    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.

  • 4. Bratel, J
    et al.
    Berggren, U
    Hirsch, Jan M
    Oral Surgery, University of Göteborg, Sweden.
    Electric or manual toothbrush?: A comparison of the effects on the oral health of mentally handicapped adults1988In: Clinical preventive dentistry, ISSN 0163-9633, Vol. 10, no 3, p. 23-26Article in journal (Refereed)
  • 5. Bächli, Heidi
    et al.
    Leiggener, Christoph
    Gawelin, Petter
    Audigé, Laurent
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Zeilhofer, Hans-Florian
    Hirsch, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Buitrago-Téllez, Carlos
    Skull base and maxillofacial fractures: two centre study with correlation of clinical findings with a comprehensive craniofacial classification system2009In: Journal of Cranio-Maxillofacial Surgery, ISSN 1010-5182, E-ISSN 1878-4119, Vol. 37, no 6, p. 305-11Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Dérand, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Virtual bending of mandibular reconstruction plates using a computer-aided design2009In: Journal of oral and maxillofacial surgery (Print), ISSN 0278-2391, E-ISSN 1531-5053, Vol. 67, no 8, p. 1640-1643Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Edman, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Odontology & Maxillofacial Surgery. Administrative Center for Public Dental Service, Falun, Sweden.
    Runow Stark, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Odontology & Maxillofacial Surgery. Department of Maxillofacial Surgery and Orofacial Medicine, Folktandvården, Karlskrona, Region Blekinge, Karlskrona, Sweden.
    Basic, Vladimir
    Pathology and Cytology Region Dalarna Falun Sweden;Department of Natural Science and Biomedicine, School of Health and Welfare Jönköping University Jönköping Sweden.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division Vi3.
    Hirsch, Jan-Michaél
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Odontology & Maxillofacial Surgery. Department of Research & Development, Folktandvården, Stockholm AB, Region Stockholm, Stockholm, Sweden.
    Dental hygienists and dentists as providers of brush biopsies for oral mucosa screening2023In: International Journal of Dental Hygiene, ISSN 1601-5029, E-ISSN 1601-5037, Vol. 21, no 3, p. 524-532Article in journal (Refereed)
    Abstract [en]

    Background

    Oral 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.

    Aim

    The 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.

    Methods

    Participants 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.

    Results

    Out 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.

    Conclusion

    Dentists 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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  • 8. Eliasson, Alf
    et al.
    Narby, Birger
    Ekstrand, Karl
    Hirsch, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Johansson, Anders
    Wennerberg, Ann
    A 5-Year Prospective Clinical Study of Submerged and Nonsubmerged Paragon System Implants in the Edentulous Mandible2010In: International Journal of Prosthodontics, ISSN 0893-2174, E-ISSN 1139-9791, Vol. 23, no 3, p. 231-238Article in journal (Refereed)
    Abstract [en]

    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. Int J Prosthodont 2010;23:231-238.

  • 9. Esposito, M
    et al.
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Lekholm, U
    Thomsen, P
    Biological factors contributing to failures of osseointegrated oral implants. (I): Success criteria and epidemiology1998In: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 106, no 1, p. 527-551Article in journal (Refereed)
    Abstract [en]

    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.

  • 10. Esposito, M
    et al.
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Lekholm, U
    Thomsen, P
    Biological factors contributing to failures of osseointegrated oralimplants. (II): Etiopathogenesis1998In: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 106, no 3, p. 721-764Article in journal (Refereed)
    Abstract [en]

    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.

  • 11. Esposito, M
    et al.
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Lekholm, U
    Thomsen, P
    Failure patterns of four osseointegrated oral implant systems1997In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 8, no 12, p. 843-847Article in journal (Refereed)
    Abstract [en]

    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.

  • 12. Farzad, Payam
    et al.
    Messo, Elias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Högteknologi revolutionerar kraniomaxillofacial kirurgi: Datornavigation ger bättre precision och färre komplikationer2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 38, p. 2362-2365Article in journal (Refereed)
    Abstract [sv]

    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.

  • 13. Hedner, E
    et al.
    Vahlne, A
    Bergström, T
    Hirsch, Jan M
    Department of Oral Surgery, University of Gothenburg, Sweden.
    Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues1993In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 22, no 5, p. 214-220Article in journal (Refereed)
    Abstract [en]

    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.

  • 14. Hedner, E
    et al.
    Vahlne, A
    Hirsch, Jan M
    Department of Oral Surgery, University of Gothenburg, Gothenburg, Sweden.
    Primary herpes simplex virus (type 1) infection delays healing of oral excisional and extraction wounds in the rat1990In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 19, no 10, p. 471-476Article in journal (Refereed)
    Abstract [en]

    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.

  • 15. Hedner, E
    et al.
    Vahlne, A
    Kahnberg, K E
    Hirsch, Jan M
    Department of Oral Surgery, University of Göteborg, Sweden.
    Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction1993In: Journal of oral and maxillofacial surgery (Print), ISSN 0278-2391, E-ISSN 1531-5053, Vol. 51, no 4, p. 370-376; discussion 377Article in journal (Refereed)
    Abstract [en]

    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.

  • 16.
    Hillbertz, Nicolette Salmon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Jalouli, Miranda M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Viral and Molecular Aspects of Oral Cancer2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 10, p. 4201-4212Article, review/survey (Refereed)
    Abstract [en]

    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).

  • 17.
    Hirsch, Jan M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Ahlström, U
    Henrikson, P A
    Heyden, G
    Peterson, L E
    Periapical surgery1979In: International journal of oral surgery, ISSN 0300-9785, Vol. 8, no 3, p. 173-185Article in journal (Refereed)
    Abstract [en]

    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.

  • 18.
    Hirsch, Jan M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Brånemark, P I
    Fixture stability and nerve function after transposition and lateralization of the inferior alveolar nerve and fixture installation1995In: British Journal of Oral & Maxillofacial Surgery, ISSN 0266-4356, E-ISSN 1532-1940, Vol. 33, no 5, p. 276-281Article in journal (Refereed)
    Abstract [en]

    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.

  • 19.
    Hirsch, Jan M
    et al.
    Department of Oral & Maxilla-Facial Surgery, University of Göteborg, Sweden.
    Ericsson, I
    Maxillary sinus augmentation using mandibular bone grafts and simultaneous installation of implants: A surgical technique1991In: Clinical Oral Implants Research, ISSN 0905-7161, E-ISSN 1600-0501, Vol. 2, no 2, p. 91-96Article in journal (Refereed)
    Abstract [en]

    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.

  • 20.
    Hirsch, Jan M
    et al.
    Departments of Oral Surgery, Clinical Pharmacology, and Pulmonary Medicine, Sahlgrens University Hospital, Göteborg, Sweden.
    Hedner, J
    Wernstedt, L
    Lundberg, J
    Hedner, T
    Hemodynamic effects of the use of oral snuff1992In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 52, no 4, p. 394-401Article in journal (Refereed)
    Abstract [en]

    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.

  • 21.
    Hirsch, Jan M
    et al.
    Department of Oral Surgery, Faculty of Odontology, Gothenburg, Sweden.
    Heyden, G
    Thilander, H
    A clinical, histomorphological and histochemical study on snuff-induced lesions of varying severity1982In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 11, no 5, p. 387-398Article in journal (Refereed)
    Abstract [en]

    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.

  • 22.
    Hirsch, Jan M
    et al.
    Department of Oral Surgery, University of Gothenburg, Sweden.
    Johansson, S L
    Effect of long-term application of snuff on the oral mucosa: an experimental study in the rat1983In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 12, no 3, p. 187-198Article in journal (Refereed)
    Abstract [en]

    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.

  • 23.
    Hirsch, Jan M
    et al.
    The Oral Surgery Emergency Clinic, Public Dental Health Service, and Dept. of Oral Surgery, University of Gothenburg, Sweden.
    Larsson, P A
    Johansson, S L
    The reversibility of the snuff-induced lesion: an experimental study in the rat1986In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 15, no 10, p. 540-543Article in journal (Refereed)
    Abstract [en]

    Snuff lesions were induced in 30 rats. Ten of the snuff-exposed rats were killed immediately after 13 months snuff exposure, as were the 10 control animals. Ten rats were killed 1 month and 10 rats 4 months after the snuff administration had ceased. The rats exposed to snuff for 13 months exhibited hyperplastic, hyperorthokeratotic epithelium with focal mild atypia, focal ulcerations and marked subepithelial fibrosis. These changes were markedly reduced or absent in rats exposed to snuff and killed after a snuff-free interval of 1 or 4 months. Similar differences between the test-groups were seen in the epithelium lining the gingival sulcus of the lower incisors. This area seems to be more sensitive to chemical exposure than the oral mucosa proper as more severe microscopical changes were seen here. Snuff exposure results in the development of a hyperplastic, reactive, reversible lesion of the oral mucosa, suggesting that snuff predominantly has promoting activity when administered for a relatively short interval of time.

  • 24.
    Hirsch, Jan M
    et al.
    Department of Oral Surgery, University of Göteborg, Sweden.
    Livian, G
    Edward, S
    Noren, J G
    Tobacco habits among teenagers in the city of Göteborg, Sweden, and possible association with dental caries1991In: Swedish Dental Journal, ISSN 0347-9994, Vol. 15, no 3, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Frome nine dental clinics within the Public Dental Service in the City of Göteborg, 2145 patients aged 14 to 19 answered a questionnaire concerning their tobacco habits. Tobacco was used in some form by 27 per cent of the patients and use increased with age. Smoking was more common among girls than among boys: 24 and 12 per cent, respectively. The statistical analyses showed that smoking as a habit and an increased number of cigarettes smoked per day are positively correlated with increases in the number of decayed, missing and filled teeth and the number of initially decayed proximal surfaces. Further, all caries epidemiological data were significantly higher among patients with tobacco habits compared to non-users. It can be concluded that there is a correlation between the tobacco habit and increased caries prevalence. However, dietary and oral habits have to be further elucidated before any definite conclusions can be made regarding the effect of the tobacco habit per se on the development of caries.

  • 25.
    Hirsch, Jan M
    et al.
    Department of Oral Surgery, University of Göteborg, Sweden.
    Svennerholm, B
    Vahlne, A
    Inhibition of herpes simplex virus replication by tobacco extracts1984In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 44, no 5, p. 1991-1997Article in journal (Refereed)
    Abstract [en]

    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.

  • 26.
    Hirsch, Jan M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thilander, H
    Snuff-induced lesions of the oral mucosa: an experimental model in the rat1981In: Journal of oral pathology, ISSN 0300-9777, Vol. 10, no 5, p. 342-353Article in journal (Refereed)
    Abstract [en]

    An experimental model in the white rat has been developed in order to study the influence of snuff on oral mucosa. A test canal in the lower lip, with one orifice buccally to the incisors and one on the lip side, was created by surgical means. The connection between the canal and the oral cavity was made to ensure the presence of saliva in the canal so that physiological conditions resembling those of the oral cavity were obtained. The canal was filled with snuff morning and night 5 days a week. The mean value for the maximal retention time of the snuff was 6 h. The animals tolerated the dose and time of exposure without signs of severe toxic symptoms. Histological examination of the canals after 9 months of exposure to snuff showed a mildly to moderately hyperplastic epithelium with hyperorthokeratosis. Locally deep proliferations of epithelium with acanthotic rete pegs could be seen. In the stratum basale hyperplasia with disturbed polarity and hyperchromatic nuclei and single mitosis were noted.

  • 27.
    Hirsch, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Odontology & Maxillofacial Surgery.
    Sandy, Ronak
    Hasséus, Bengt
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division Vi3.
    A paradigm shift in the prevention and diagnosis of oral squamous cell carcinoma.2023In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 52, no 9, p. 826-833Article in journal (Refereed)
    Abstract [en]

    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.

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  • 28.
    Hirsch, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Leiggener, C
    Messo, Elias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Acosta, Rojas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Krol, Z
    Buitrage-Tellez, CH
    Reconstruction of the temperomandibular joint with free fibula microvascular flaps without and with surgical guides2009In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 4, no Suppl 1, p. S226-S227Article in journal (Refereed)
  • 29.
    Hirsch, Jan-Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Wallström, Mats
    Carlsson, Anders-Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Oral cancer in Swedish snuff dippers2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 8, p. 3327-3330Article in journal (Refereed)
    Abstract [en]

    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.

  • 30.
    Hirsch, Jan-Michaél
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Odontology & Maxillofacial Surgery. Folktandvården Stockholms län AB, huvudkontoret, Forsknings- och utbildningsavd.
    Haj-Hosseini, Neda
    Linköpings universitet, Avdelningen för medicinsk teknik.
    Krüger Weiner, Carina
    Folktandvården Stockholms län AB, Eastmaninstitutet, Käkkirurgiska kliniken..
    Hasséus, Bengt
    Avd för oral medicin och patologi, inst för odontologi, Sahlgrenska akademin, Göteborgs universitet..
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Icke-invasiv kontroll av cellförändringar i munslemhinnan2021In: Tandläkartidningen, ISSN 0039-6982, no 9, p. 48-55Article, review/survey (Refereed)
  • 31.
    Huo, Jinxing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Dérand, Per
    Department of Oral and Maxillofacial Surgery, Skåne University Hospital.
    Rännar, Lars-Erik
    Sports Tech Research Centre, Mid Sweden University.
    Hirsch, Jan-Michaél
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Gamstedt, E. Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Failure location predictoin by finite element analysis for an additive manufactured mandible implant2015In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, no 9, p. 862-869Article in journal (Refereed)
    Abstract [en]

    In order to reconstruct a patient with a bone defect in the mandible, a porous scaffold attached to a plate, both in a titanium alloy, was designed and manufactured using additive manufacturing. Regrettably, the implant fractured in vivo several months after surgery. The aim of this study was to investigate the failure of the implant and show a way of predicting the mechanical properties of the implant before surgery. All computed tomography data of the patient were preprocessed to remove metallic artefacts with metal deletion technique before mandible geometry reconstruction. The three-dimensional geometry of the patient's mandible was also reconstructed, and the implant was fixed to the bone model with screws in Mimics medical imaging software. A finite element model was established from the assembly of the mandible and the implant to study stresses developed during mastication. The stress distribution in the load-bearing plate was computed, and the location of main stress concentration in the plate was determined. Comparison between the fracture region and the location of the stress concentration shows that finite element analysis could serve as a tool for optimizing the design of mandible implants.

  • 32.
    Huo, Jinxing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Mechanics.
    Hirsch, Jan M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Odontology & Maxillofacial Surgery.
    Gamstedt, E. Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Mechanics.
    Analytical Study of Stress Distributions around Screws in Flat Mandibular Bone under In-Plane Loading2023In: Bioengineering, E-ISSN 2306-5354, Vol. 10, no 7, article id 786Article in journal (Refereed)
    Abstract [en]

    A known complication for mechanically loaded bone implants is the instability due to screw loosening, resulting in infection and the non-union of fractures. To investigate and eventually prevent such bone degradation, it is useful to know the stress state in the bone around the screw. Considering only in-plane loadings and simplifying the mandibular bone into an orthotropic laminated plate, the analysis was reduced to a two-dimensional pin-loaded plate problem. An analytic model, based on the complex stress analysis, was introduced to the bone biomechanics field to obtain the stress distributions around the screw hole in the bone. The dimensionless normalized stresses were found to be relatively insensitive to the locations of the screw hole over the mandible. Parametric analyses were carried out regarding the friction coefficient and load direction. It was found that the load direction had a negligible influence. On the contrary, the friction coefficient had a significant effect on the stress distributions. Whether the screw was well bonded or not thus played an important role. The proposed analytic model could potentially be used to study bone failure together with stress-based failure criteria.

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  • 33. Ibrahim, S O
    et al.
    Johannessen, A C
    Idris, A M
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Vasstrand, E N
    Magnusson, B
    Nilsen, R
    Immunohistochemical detection of p53 in non-malignant and malignant oral lesions associated with snuff dipping in the Sudan and Sweden1996In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 68, no 6, p. 749-753Article in journal (Refereed)
    Abstract [en]

    Immunohistochemistry was used to examine the expression of p53 in pre-malignant oral lesions and oral squamous-cell carcinomas (SCCs) from Swedish and Sudanese snuff-dippers, as well as in pre-malignant oral lesions and oral SCCs from non-snuff-dippers from the Sudan, Sweden and Norway. Of the 14 SCCs from Sudanese snuff-dippers, 21% (3/14) expressed p53. Of the 14, 60 and 41 SCCs from non-snuff-dippers from the Sudan, Sweden and Norway, 64% (9/14), 65% (39/60) and 68% (28/41) expressed p53, respectively. A statistically significant difference in expression of p53 was found in SCCs from Sudanese snuff-dippers compared to those from non-snuff-dippers from all/or any of the 3 countries. None of the suspected pre-malignant oral lesions from Sudanese snuff dippers or non-snuff-dippers expressed p53. Only 2 out of the 15 oral fibro-epithelial hyperplastic lesions from Swedish snuff-dippers expressed p53. Some of the oral epithelial dysplastic lesions, as well as the carcinoma in situ lesions from Norwegian non-snuff-dippers, expressed p53, while the oral fibro-epithelial hyperplastic lesions did not. The low relative frequency of p53 expression found in oral SCCs from snuff-dippers compared to those from non-snuff-dippers might suggest differences in mechanisms of oncogenic action induced by snuff. Alternatively, the pathogenesis of malignant oral lesions from snuff-dippers may follow a p53-independent pathway. In view of the unusually high levels of the tobacco-specific nitrosamines (TSNA) found in the type of snuff used in the Sudan, investigations of p53 mutations or oncogenes are needed.

  • 34. Idris, AM
    et al.
    Ibrahim, SO
    Vasstrand, EN
    Johannessen, AC
    Lillehaug, JR
    Magnusson, B
    Wallstrom, M
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Nilsen, R
    The Swedish snus and the Sudanese toombak: are they different?1998In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 34, no 6, p. 558-566Article in journal (Refereed)
    Abstract [en]

    In Sweden, snuff (locally known as snus), was introduced since the year 1637. Presently, Sweden has the highest per capita consumption and sale figures of snuff in the world, and the habit is becoming increasingly popular. Snus is manufactured into a dry form used in the nasal cavity and a moist form used in the oral cavity. Snus manufactured for oral use is a moist ground tobacco of Dark Kentucky or Virginia species mixed with an aqueous solution of water and other blending ingredients. This form of snuff is found in two types: (1) loose and (2) portion-bag-packed. These are the most widely used. The loose moist form (1–2 g a quid) is the most popular type consumed by 73% of the males, followed by the portion-bag-packed form (0.5–1 g a quid), consumed by 13% of the males, while 14% of the males are mixed users. The majority of snus users place the quid in the vestibular area of the upper lip, and the prevalence among persons 15 years of age or older is 15.9% among males and 0.2% among females. The pH of snus has declined from a previous range of 8–9 to a range of 7.8–8.5, moisture content ranges 35–60% and nicotine content is in the order of 5–11 mg/g dry wt tobacco-specific N-nitrosamines (TSNAs) in micrograms (N′-nitrosonornicotine: NNN 5–9; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: NNK 1–2; N′-nitrosoanatabine: NAT 2–5). In the Sudan, snuff, locally known as toombak, was introduced approximately 400 years ago. It is always processed into a loose moist form, and its use is widespread in the country. Tobacco used for manufacture of toombak is of the species Nicotiana rustica, and the fermented ground powder is mixed with an aqueous solution of sodium bicarbonate. The resultant product is moist, with a strong aroma, highly addictive and its use is widespread particularly among males. Its pH range is 8–11, moisture content ranges 6–60% and nicotine content is from 8 to 102 mg/g dry wt, and TSNAs contents in micrograms (NNN 420–1 550; NNK 620–7 870; NAT 20–290). Snus and toombak dippers develop a clinically and histologically characteristic lesion at the site of dipping. Probably due to control of the TSNAs in snus, this type of snuff is associated with a lower risk of cancer of the oral cavity (relative risk: RR 5–6-fold), whereas the risk for cancer of the oral cavity among toombak users was high (RR 7.3–73.0-fold). In conclusion, the two snuff products significantly differ in many aspects. Most notable differences are tobacco species, fermentation and ageing, nicotine and TSNAs content, pH, expression of the p53 tumour supressor gene, and keratin types 13, 14, and 19. It was, therefore, the object of the present study to highlight the oral health hazards of toombak, and to compare it with snus regarding the aforementioned differences.

  • 35.
    Jalouli, Jamshid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Ibrahim, Salah O.
    Mehrotra, Ravi
    Jalouli, Miranda M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sapkota, Dipak
    Larsson, Per-Anders
    Hirsch, Jan M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India2010In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 130, no 11, p. 1306-1311Article in journal (Refereed)
    Abstract [en]

    Conclusion: There is a high prevalence of human papilloma viruses (HPV) in oral submucous fibrosis (OSMF) and the etiologic implication of this finding warrants further studies. Objective: The prevalence of oral squamous cell carcinoma (OSCC) and OSMF is high in India, and the diseases are partly attributed to high consumption of betel quid containing areca nut and tobacco. This study investigated the prevalence of HPV, herpes simplex virus (HSV), and Epstein-Barr virus (EBV) DNA in two groups of patients using betel quid with tobacco, those with OSMF (n = 12) and those with OSCC (n = 62). Methods: DNA was extracted from all the samples and viral genome was examined by PCR/DNA sequencing. HPV-positive samples were analyzed separately for the high-risk types HPV 16 and 18. Results: HPV DNA, HSV DNA, and EBV DNA were detected in 11 (91%), 1 (8%), and 3 (25%) of the 12 samples from patients with OSMF compared with 15 (24%), 3 (5%), and 18 (29%), respectively, from 62 patients with OSCC. HPV 16 and 18 DNA was detected in 8/12 (67%) in the OSMF group and 10/62 (16%) in the OSCC group. The difference between presence of HPV DNA in OSMF and OSCC groups was statistically significant, while the difference between HSV and EBV DNA content in OSMF and OSCC groups was insignificant.

  • 36.
    Jalouli, Miranda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hasséus, Bengt
    Öhman, Jenny
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Nested PCR for detection of HSV-1 in oral mucosa2015In: Medicina Oral, ISSN 1698-4447, E-ISSN 1698-6946, Vol. 20, no 6, p. E664-E669Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC).

    MATERIAL AND METHODS: We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing.

    RESULTS: HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant.

    CONCLUSIONS: We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected.

  • 37.
    Jalouli, Miranda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Ibrahim, Salah O.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Comparison Between Single PCR and Nested PCR in Detection of Human Papilloma Viruses in Paraffin-embedded OSCC and Fresh Oral Mucosa2015In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 29, no 1, p. 65-70Article in journal (Refereed)
    Abstract [en]

    Background: Infection with human papilloma virus (HPV) has been implicated as one of the risk factors for the development of oropharyngeal cancer. Many different HPV tests exist, and information regarding their specific technical, analytical, and clinical properties is increasing. Aim: This study aimed to compare the level of detection of HPV using two reliable polymerase chain reaction (PCR) methods, nested PCR (NPCR) and single PCR (SPCR), in archival paraffin-embedded oral squamous cell carcinoma (OSCC) samples and fresh oral mucosa specimens. Materials and Methods: The presence of HPV genome in two groups of tissue samples was analyzed: (i) 57 paraffin-embedded OSCC samples from Sudan and (ii) eight healthy fresh oral mucosal samples from Swedish volunteers. The specimens were tested by SPCR with primer pair MY9/MY11 and NPCR using GP5+/GP6+ primer sets. Results: Eighteen (32%) out of the 57 paraffin-embedded OSCC samples, and five (62%) out of the eight fresh clinically healthy samples were found to be HPV-positive with NPCR. With SPCR, four (7%) out of the paraffin-embedded OSCC samples were HPV-positive. A statistically significant difference between HPV-positive and -negative samples was found when comparing NPCR and SPCR in OSCC and fresh oral mucosa (p<0.0001). The comparative test between SPCR and NPCR showed 100% sensitivity and 69% specificity for OSCC. Conclusion: The use of the GP5+/GP6+ nested PCR increased the positivity rate, efficiency rate and sensitivity of HPV detection in oral samples significantly and should be considered as the method of choice.

  • 38.
    Jalouli, Miranda M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sapkota, Dipak
    Ibrahim, Salah O.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hirsch, Jan-M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Differential Expression of Apoptosis, Cell Cycle Regulation and Intermediate Filament Genes in Oral Squamous Cell Carcinomas Associated with Toombak Use in Sudan2011In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 31, no 10, p. 3345-3351Article in journal (Refereed)
    Abstract [en]

    Previously we used microarray genomic hybridization technology to explore genome-wide profiles of chromosomal aberrations in samples of oral squamous cell carcinomas (OSCCs) and paired normal controls. Based on these findings, 9 genes related to apoptosis, cell cycle regulation and intermediate filament proteins were selected and their differential expression status was examined by real-time quantitative RT-PCR in 26 samples of Sudanese OSCCs and their matched normal controls. The findings were correlated with the habit of toombak use. The mRNA levels of Bcl2, keratin 1, keratin 13 and p53 were significantly lower and the level of survivin was significantly higher in the OSCC samples of the toombak users compared to their paired control samples. A significant down-regulation in keratin I and keratin 13 expression levels was found in the OSCC samples of the non-toombak users compared to their normal control samples. The differential expression of genes related to apoptosis, cell cycle regulation and types I and II keratin could be useful diagnostic markers and provide valuable information for the understanding of oral malignancy in relation to toombak use.

  • 39.
    Jalouli, Miranda M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Öhman, J
    Hasseús, B
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Association of Human Papilloma Virus infection in healthy oral mucosa, oral dysplasia and oral squamous cell carcinoma2015In: Journal of Oral Health and Dental Management, ISSN 1583-5588, Vol. 14, no 5Article in journal (Refereed)
    Abstract [en]

    Aims: Human papillomavirus (HPV) is an important risk factor for development of oral cancer; however, the integrational status of the virus into the host DNA association between HPV infection and oral squamous cell carcinoma (OSCC) is still uncertain has not been investigated to the same extent. The objective of the present study was to investigate the prevalence of consensus HPV, and HPV-16 and its integration status, in healthy oral mucosa, oral epithelial dysplasia (OED), and OSCC samples.Materials and Methods: The study material consisted of 26 fresh, normal oral mucosa samples, and 53 and 27 paraffin-embedded OED and OSCC samples, respectively. The specimens were DNA extracted and investigated for the presence of HPV, and HPV-16 and its integration status, by polymerase chain reaction (PCR) and DNA sequencing.Results: Thirty-eight (72%) of the 53 paraffin-embedded OED samples, 16 (59%) of the 27 OSCC samples, and 12 (46%) of the 26 control samples were found to be HPV-DNA positive, with nested PCR (NPCR). Further, HPV-16 was detected in 31 (82%), 15 (94%), and 0 (0%) HPV-positive OED cases, HPV-positive OSCC cases, and controls, respectively. Integration was observed in 26/31 (84%) and 13/15 (87%) of the HPV-16-positive OED and OSCC cases, respectively. A statistically significant difference was found comparing prevalence of HPV-16 in controls with that in both OED and OSCC samples (P<0.005). A statistically significant difference was also found comparing prevalence of integrated and episomal viral forms comparing OED and OSCC samples (P<0.005).Conclusion: The high prevalence of HPV and high-risk HPV-16 in OED and OSCC samples suggests a potential aetiologic role for the virus in OSCC.

  • 40. Johansson, P
    et al.
    Berggren, U
    Hakeberg, M
    Hirsch, Jan M
    Department of Endodontology and Oral Diagnosis, University of Göteborg, Sweden.
    Measures of dental beliefs and attitudes: their relationships with measures of fear1993In: Community Dental Health, ISSN 0265-539X, Vol. 10, no 1, p. 31-39Article in journal (Refereed)
    Abstract [en]

    Emergency dental and fearful dental patients were questioned in order to investigate the relationship between dental fear and different dental beliefs. The instruments used were the dental anxiety scale and the dental beliefs survey. The study also evaluated a Swedish version of the beliefs survey. The mean anxiety scale scores were 9.4 for emergency and 16.8 for fearful patients. The average beliefs survey item values ranged from 1.6 to 2.6 and 1.7 to 3.8 among the two groups respectively. There were clinical meaningful and statistically significant correlations between the anxiety scale and the beliefs survey. Each of the four dimensions of the beliefs survey (communication, control, belittlement and trust), also correlated with the anxiety scale of which the most clearly defined was belittlement.

  • 41. Johansson, S L
    et al.
    Hirsch, Jan M
    Department of Oral Surgery, University of Göteborg, Göteborg, Sweden.
    Johnson, D R
    Effect of repeated oral administration of tobacco snuff on natural killer-cell activity in the rat1991In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 36, no 6, p. 473-476Article in journal (Refereed)
    Abstract [en]

    The possible immune effect of oral snuff was investigated. In male adult rats, oral snuff given for 15 weeks significantly decreased NK-cell activity in peripheral blood against murine NK cell-sensitive target cells (YAC-1 lymphoma).

  • 42. Johansson, S L
    et al.
    Hirsch, Jan M
    Department of Oral Surgery, University of Göteborg, Sweden.
    Larsson, P A
    Saidi, J
    Österdahl, B G
    Snuff-induced carcinogenesis: effect of snuff in rats initiated with 4-nitroquinoline N-oxide1989In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 49, no 11, p. 3063-3069Article in journal (Refereed)
    Abstract [en]

    A canal in the lower lip to function as a reservoir for snuff was surgically created in 150 male Sprague-Dawley rats. The animals were randomized into five groups of 30 each: Group I received snuff twice a day, 5 days a wk; Group II was painted with propylene glycol (solvent control) on the hard palate 3 times a wk during 4 wk; Group III underwent painting on the hard palate with 4-nitroquinoline N-oxide (4-NQO) dissolved in propylene glycol, 3 times a wk for 4 wk; Group IV received 4-NQO as in Group III followed by snuff application as in Group I; and Group V received a cotton pellet dipped in saline twice a day, 5 days a wk. Treatment continued for up to 108 wk. There was no significant difference in mean survival time between the groups. Squamous cell tumors of the lip, oral and nasal cavities, esophagus, and forestomach were seen only in Groups I, III, and IV. Nine tumors of these organs were found in Group I (six carcinomas and three papillomas), nine in Group III (seven carcinomas and two papillomas), and ten in Group IV (eight carcinomas and two papillomas). The difference between each of these groups and the control groups (II and V) with regard to tumor incidence is statistically significant (P less than 0.05). In Group I, four oral cavity or lip carcinomas were found in 29 rats, a significant difference in relation to control rats (P less than 0.05). In addition, hyperplastic lesions of the lip, palate, and forestomach were significantly more common in Groups I and IV compared with Groups II, III, and V. The study has shown that snuff and 4-NQO by themselves have the potential to induce malignant tumors. Initiation with 4-NQO followed by snuff did not significantly enhance tumor formation.

  • 43.
    Kharazmi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Carlsson, Anders-Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Modig, Maria
    Bjornstad, Lillemor
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Surgical approach to snus-induced injury of the oral mucosa2014In: Journal of Oral Science, ISSN 1343-4934, E-ISSN 1880-4926, Vol. 56, no 1, p. 91-94Article in journal (Refereed)
    Abstract [en]

    Snus (Swedish moist snuff) causes lesions in the oral mucosa at the location where pinches are regularly placed. In addition, some patients develop irreversible local gingival recession and sometimes ulcers with perforations to the roots. Such injuries lead to denuded roots that are at risk for caries and periodontal disease, with subsequent esthetic consequences. Therapy for irreversible local gingival recession is currently lacking. In the present report, we describe two cases of successful surgical treatment for irreversible lesions caused by snus.

  • 44. Khonsari, R H
    et al.
    Friess, M
    Nysjö, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Odri, G
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Nyström, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Messo, Elias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hirsch, Jan M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Cabanis, E A M
    Kunzelmann, K H
    Salagnac, J M
    Corre, P
    Ohazama, A
    Sharpe, P T
    Charlier, P
    Olszewski, R
    Shape and volume of craniofacial cavities in intentional skull deformations2013In: American Journal of Physical Anthropology, ISSN 0002-9483, E-ISSN 1096-8644, Vol. 151, no 1, p. 110-119Article in journal (Refereed)
    Abstract [en]

    Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.

  • 45.
    Koriakina, Nadezhda
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Sladoje, Natasa
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Ramqvist, Eva Darai
    Pathology and Cytology, Karolinska Institute, Stockholm, Sweden.
    Hirsch, Jan M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Runow Stark, Christina
    Public Dental Service, Södersjukhuset, Stockholm, Sweden.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Visualization of convolutional neural network class activations in automated oral cancer detection for interpretation of malignancy associated changes2019In: 3rd NEUBIAS Conference, Luxembourg, 2-8 February 2019, 2019, , p. 1Conference paper (Other academic)
    Abstract [en]

    Introduction: Cancer of the oral cavity is one of the most common malignancies in the world. The incidence of oral cavity and oropharyngeal cancer is increasing among young people. It is noteworthy that the oral cavity can be relatively easily accessed for routine screening tests that could potentially decrease the incidence of oral cancer. Automated deep learning computer aided methods show promising ability for detection of subtle precancerous changes at a very early stage, also when visual examination is less effective. Although the biological nature of these malignancy associated changes is not fully understood, the consistency of morphology and textural changes within a cell dataset could shed light on the premalignant state. In this study, we are aiming to increase understanding of this phenomenon by exploring and visualizing what parts of cell images are considered as most important when trained deep convolutional neural networks (DCNNs) are used to differentiate cytological images into normal and abnormal classes.

    Materials and methods: Cell samples are collected with a brush at areas of interest in the oral cavity and stained according to standard PAP procedures. Digital images from the slides are acquired with a 0.32 micron pixel size in greyscale format (570 nm bandpass filter). Cell nuclei are manually selected in the images and a small region is cropped around each nucleus resulting in images of 80x80 pixels. Medical knowledge is not used for choosing the cells but they are just randomly selected from the glass; for the learning process we are only providing ground truth on the patient level and not on the cell level. Overall, 10274 images of cell nuclei and the surrounding region are used to train state-of-the-art DCNNs to distinguish between cells from healthy persons and persons with precancerous lesions. Data augmentation through 90 degrees rotations and mirroring is applied to the datasets. Different approaches for class activation mapping and related methods are utilized to determine what image regions and feature maps are responsible for the relevant class differentiation.

    Results and Discussion:The best performing of the observed deep learning architectures reaches a per cell classification accuracy surpassing 80% on the observed material. Visualizing the class activation maps confirms our expectation that the network is able to learn to focus on specific relevant parts of the sample regions. We compare and evaluate our findings related to detected discriminative regions with the subjective judgements of a trained cytotechnologist. We believe that this effort on improving understanding of decision criteria used by machine and human leads to increased understanding of malignancy associated changes and also improves robustness and reliability of the automated malignancy detection procedure.

  • 46.
    Korytowska, Magdalena
    et al.
    NÄL Hosp, Publ Dent Serv, Clin Orofacial Med, Uddevalla, Sweden.
    Schwab, Gabriela
    Inst Trop Med Sao Paulo, Sch Med, Lab Virol, Sao Paulo, Brazil.
    Giglio, Daniel
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden.
    Hirsch, Jan-Micháel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Publ Dent Serv Reg Stockholm, Dept Res & Dev, Stockholm, Sweden.
    Holmberg, Erik
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden.
    Kjeller, Göran
    Univ Gothenburg, Inst Odontol, Sahlgrenska Acad, Dept Oral & Maxillofacial Surg, Gothenburg, Sweden.
    Sand, Lars
    Univ Oslo, Fac Odontol, Dept Oral Biol, Oslo, Oslo, Norway.
    Wallström, Mats
    Univ Gothenburg, Inst Odontol, Sahlgrenska Acad, Dept Oral & Maxillofacial Surg, Gothenburg, Sweden.
    Öhman, Jenny
    Univ Gothenburg, Inst Odontol, Sahlgrenska Acad, Dept Oral Med & Pathol, Gothenburg, Sweden.
    Braz-Silva, Paulo
    Inst Trop Med Sao Paulo, Sch Med, Lab Virol, Sao Paulo, Brazil; Univ Sao Paulo, Sch Dent, Dept Stomatol, Sao Paulo, Brazil.
    Hasséus, Bengt
    Univ Gothenburg, Inst Odontol, Sahlgrenska Acad, Dept Oral Med & Pathol, Gothenburg, Sweden; Publ Dent Hlth Serv, Clin Oral Med, Gothenburg, Sweden.
    Patient-reported pain after surgical removal of leukoplakia: an observational 1-year follow-up study2021In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 79, no 5, p. 383-389Article in journal (Refereed)
    Abstract [en]

    Objective

    Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL.

    Methods

    Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up.

    Results

    Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022).

    Conclusion

    We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.

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  • 47.
    Kumar, Vinay V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hirsch, Jan M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Denture Guided Epithelial Regeneration: metod för att skapa keratiniserad gingiva i anslutning till implantat2020In: Tandläkartidningen, ISSN 0039-6982, no 10, p. 60-65Article in journal (Refereed)
  • 48. Larsson, P A
    et al.
    Hirsch, Jan M
    Department of Oral Surgery, University of Göteborg, S-413 46 Göteborg, Sweden.
    Gronowitz, J S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Medical Genetics.
    Vahlne, A
    Inhibition of herpes simplex virus replication and protein synthesis by non-smoked tobacco, tobacco alkaloids and nitrosamines1992In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 37, no 11, p. 969-978Article in journal (Refereed)
    Abstract [en]

    Inhibitory effects of snuff extract and the tobacco chemicals nicotine, anabasine, diethyl-N-nitrosamine (DEN), and the tobacco-specific nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on herpes simplex virus type 1 (HSV-1) replication in vitro and on HSV-1 protein synthesis in infected cells were analysed. Snuff extract and nicotine caused a significant reduction of HSV-1 attachment to cell membranes whereas anabasine, DEN, NNN and NNK did not affect adsorption of HSV-1. Virus production assays in the presence of snuff added after virus adsorption resulted in a significantly reduced production of virus at low multiplicities of infection (MOI), but at high MOI the inhibitory effect of snuff extract was less pronounced. DEN, NNN and NNK only affected virus production at toxic concentrations. Nicotine and anabasine reduced virus production in non-toxic doses but not at the concentrations present in snuff extract. In HSV-infected cells exposed to snuff extract, the immediate early (α-) infected cell proteins (ICPs) 4 and 27 (as well as the early (β-) ICPs 6 and 8) were markedly increased, whereas the late (γ-) ICPs 5, 11 and 29 were reduced. Nicotine had a less pronounced stimulating effect on the production of α-proteins but no detectable effect on production of β- or -γ-proteins. Anabasine, DEN, NNN and NNK did not affect HSV protein synthesis at non-toxic concentrations. Synthesis of thymidine kinase and DNA polymerase was significantly reduced by snuff extract. Also nicotine and anabasine affected thymidine kinase and DNA polymerase but only at toxic concentrations. The production of the cellular protein actin, which almost disappears a few hours after HSV-1 infection, remained at a significant level in HSV-infected cells exposed to snuff. Thus snuff extract blocks the replicative cycle of HSV at an early stage, which results in an increased production of α-proteins in the infected cells and in prolonged maintenance of cellular functions. This may be of importance for HSV-induced transformation and the development of HSV-associated tumours.

  • 49. Larsson, P A
    et al.
    Johansson, S L
    Hirsch, Jan M
    Oral Surgery, University of Göteborg, Sweden.
    Vahlne, A
    Effects of acyclovir on herpes simplex virus type 1 infection in mice treated with 12-O-tetradecanoylphorbol 13-acetate1989In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 70, no 7, p. 1773-1778Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to determine whether infectious herpes simplex virus type 1 (HSV-1) has tumorigenic properties and, if so, whether inhibition of the cytolytic replicative cycle of the virus after infection enhances tumour development. Eighty mice were subjected to repeated inoculation of HSV-1 on their upper lips after scarification, and systemic administration of acyclovir (ACV). 12-O-tetradecanoylphorbol 13-acetate (TPA) was used as the tumour promoter. The tumour incidence was compared to control groups each of 40 mice that were either not treated with ACV, not treated with TPA, not infected with HSV or only scarified. In the virus-infected group treated with ACV and TPA, 25% of the animals developed tumours. In the HSV-infected group treated with TPA only, 25% of the animals also developed tumours. The uninfected animals which were not treated with TPA developed tumours to a significantly lesser degree. In conclusion, the combined effects of HSV-1 and TPA, with or without ACV treatment, resulted in a significant increase in the number of tumours in comparison to the control groups.

  • 50. Larsson, P A
    et al.
    Johansson, S L
    Vahlne, A
    Hirsch, Jan M
    Department of Oral Surgery, University of Gothenburg, Sweden.
    Snuff tumorigenesis: effects of long-term snuff administration after initiation with 4-nitroquinoline-N-oxide and herpes simplex virus type 11989In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 18, no 4, p. 187-192Article in journal (Refereed)
    Abstract [en]

    The tumor promoting effects of snuff was studied in Lewis rats initiated with 4-nitroquinoline-N-oxide (4-NQO) and Sprague Dawley rats repeatedly inoculated with herpes simplex virus type 1 (HSV-1). The test substances were administered in a surgically created canal in the lower lips of the rats. There were 15 rats in each test group and 10 rats in the control group. In the groups treated with 4-NQO and 4-NQO + snuff, 8 and 12 tumors (5 and 9 malignant) were found, respectively. In the group subjected to HSV-1 only, 3 tumors were found (2 malignant), in the group subjected to snuff only, 4 tumors were found (3 malignant) and in the group subjected to the combination of HSV-1 and snuff, 13 tumors were found (7 malignant). In the control group only one malignancy was found. The study did not show any promoting effects of snuff in the oral cavity after initiation with 4-NQO. Neither was there any increase in the number of oral tumors in rats treated with HSV-1 and snuff. However, there was a marked increase in the number of malignant tumors outside the oral cavity in the group treated with HSV-1 and snuff, underlining the importance of interactions between these two agents in the development of malignant lesions.

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