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- Sundell, Anna Lena, 1970-
(författare)
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Children with orofacial clefts : dental caries and health-related quality of life
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. The current understanding on caries and enamel developmental defects prevalence and frequency, caries risk, health-related quality life (HRQoL) and stress response in young children with cleft lip and/or palate (CL/P) are sparse. In this thesis these aspects were investigated in 5- and 10- year-old children with CL/P in comparison to non-cleft children in the same ages.Design. The studies in this thesis have a cross-sectional case-control design. Participants. The study group consisted of 139 children with CL/P (80 children aged 5 years and 59 aged 10 years) and 313 non-cleft controls (144 children aged 5 years and 169 aged 10 years).Method. Caries was scored according to International Caries Detection and Assessment System (ICDAS II) and developmental enamel defects were measured as presence and frequency of hypoplasia and hypomineralization. Oral hygiene was assessed using Quigley-Hein plaque index. Stimulated saliva samples were analyzed for mutans streptococci, lactobacilli, buffering capacity and secretion rates. Information regarding children’s oral hygiene routines, dietary habits and fluoride exposure were collected with questionnaires. Caries risk was evaluated with algorithm-based software, Cariogram while HRQoL was perceived with KIDSCREEN-52. Stress response was analyzed with cortisol concentration in saliva at three different time points using a commercial competitive radioimmunoassay.Results. Caries prevalence (36% versus 18%) and caries frequency (1.2 dmfs versus 0.9 dmfs) was significantly higher in 5-year-old children with CL/P in comparison to non-cleft controls. In 10-yearolds no significant difference was found between children with CL/P and non-cleft controls in caries prevalence (47% versus 38%) or in caries frequency (0.7 DMFS versus 0.5 DMFS). Children with CL/P had significantly higher prevalence of enamel defects, higher counts of salivary lactobacilli and less good oral hygiene. The odds of being categorized with high caries risk were elevated in children with CL/P. Children with CL/P had similar HRQoL and salivary cortisol concentrations as non-cleft controls. However, 10-year-old boys with CL/P had significantly higher cortisol concentrations in the evening than non-cleft boys.Conclusions. Preschool children with CL/P seem to have more caries in the primary dentition than non-cleft controls. Children with CL/P had increased odds of being categorized as high caries risk individuals compared to controls. Some of the contributing factors seem to be higher prevalence of enamel defects, impaired oral hygiene and elevated salivary lactobacilli. Furthermore, as measured with the help of cortisol concentrations in saliva, children with CL/P were not more stressed than noncleft controls and their HRQoL was comparable to a European norm population. It appears that regular comprehensive preventive oral care in children with CL/P is effective in preventing caries development in permanent teeth. However, children with CL/P are at risk of caries development and preventive oral care should be implemented and started earlier than today.
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- Wilms, Torben, 1973-
(författare)
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Squamous cell carcinoma of the head and neck, focusing on Epstein-Barr-virus, programmed cell death ligand 1 and serum lipoproteins
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Squamous cell carcinoma of the head and neck (SCCHN)comprises a large group of tumours including the oral cavity and nasopharyngealarea, and typically affects older males in association with alcohol/tobacco usage.Within the oral cavity, the mobile tongue is the most common site for tumourdevelopment. The incidence of squamous cell carcinoma of the oral tongue(SCCOT) is increasing in younger people, which has been suggested to associatewith other than the traditional risk factors for this disease. Two common humanoncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV)are connected to certain types of SCCHN, in oropharynx and nasopharynxrespectively. The receptor programmed cell death 1 (PD)-1 and its ligandprogrammed cell death ligand 1 (PD-L1) are particularly relevant in immunecheckpoint control, and elevated levels have been seen in various cancer types. Alink between hyperlipidemia and cancer risk has previously been suggested. Theaim of this thesis was to investigate risk factors and prognostic features forSCCHN, by focusing on EBV, PD-L1 and serum lipoproteins.Materials and methods: Ninety-eight cases of SCCOT and 15 cases of tonsillarsquamous cell carcinoma were examined for the presence of EBV-encodedribonucleic acids (EBERs), EBV deoxyribonucleic acid (DNA) and the proteinEBV-encoded nuclear antigen-1 (EBNA-1), using in situ hybridisation,polymerase chain reaction (PCR) and immunohistochemistry respectively. Onehundred and one cases of SCCOT were examined for expression of PD-L1 intumour and surrounding immune cells using Ventana SP263immunohistochemistry assay and a QuickScore (QS) method. An estimation oftumour-infiltrating immune cells was also performed in 25 of the patients.Circulating levels of PD-L1 were measured using an electrochemiluminescenceassay platform in serum from 30 patients. Finally, serum samples from 106patients and 28 healthy controls were investigated for levels of total cholesterol,low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides andlipoprotein(a).Results: In the first study, using an in situ hybridisation kit no EBER transcriptswere detected. No EBV DNA was identified with PCR analysis, andimmunohistochemistry for EBNA-1 was also negative. In the second study, highertumour cell PD-L1 levels were found in females than males (p = 0.019). Forpatients with low PD-L1 in tumour cells, better survival was shown in males thanfemales (overall survival p = 0.021, disease-free survival p = 0.020). Tumourinfiltrating natural killer (NK) T cells, immature dendritic cells (DCs) and M1macrophages correlated positively with tumour cell PD-L1 (p < 0.05). In the laststudy, the only lipoprotein showing significant difference in concentration iiibetween healthy controls and patients was HDL (p = 0.012). Kaplan-Meiersurvival curves showed that patients with high levels of total cholesterol or LDLhad better survival than patients with normal levels (p = 0.028 and p = 0.007respectively). Adjusting for the effects of age at diagnosis, TNM stage and weightchange, multivariate Cox regression models showed LDL to be an independentprognostic factor for both overall (p = 0.010) and disease-free survival (p =0.018).Conclusion: We excluded EBV as a potential player in SCCOT in both old andyoung patients and highlight the importance of appropriate controls for EBVencoded RNA in-situ hybridization (EBER-ISH) when investigating EBV inhuman diseases. Regarding PD-L1, our data supported the significance of genderon tumour cell PD-L1 expression and demonstrated combined effects of genderand PD-L1 levels on clinical outcome in patients with SCCOT. Data also indicatedthe involvement of specific immune cell types in PD-L1-regulated immuneevasion. Looking at serum lipoproteins, we found high LDL levels to be beneficialfor survival outcome in patients with SCCHN. Furthermore, the use of cholesterollowering medicine for prevention or management of SCCHN needs to be carefullyevaluated.
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| 6. |
- Walladbegi, Java
(författare)
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Preclinical Studies for Cryoprevention of Oral Mucositis
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oral mucositis (OM) is a debilitating adverse effect, with a prevalence of up to 80% in patients with cancer who are conditioned with high-dose chemotherapy prior to hematopoietic stem cell transplantation. In its mildest form, OM is characterized by erythema. However, as it worsens, it can give rise to painful ulcerations in the oral mucosa. This may lead to an increased need for analgesics (and sometimes intravenous morphine) for pain relief, and there is an increased risk of systemic infections. Overall, OM-related complications entail increased health care costs. In fact, despite its frequency, impact on patients, and healthcare and economic burdens, current literature indicates few evidence-based interventions with confirmed efficacy for the prevention of OM. In response to this gap in the knowledge, a novel intraoral cooling device has been developed. The long-term goal of the research described in this thesis is to establish an effective and well-tolerated method for cryoprevention of OM. The specific aims of this thesis were to: (i) investigate whether cooling, using a constant low temperature, is effective for oral tissue preservation; (ii) develop an animal model to study the early events which precede OM; (iii) assess the effectiveness of a novel intraoral cooling device as a cryopreventive method; (iv) evaluate whether local cooling affects the oral hemodynamics; and (v) establish how a research protocol should be designed for a randomized controlled trial to evaluate cryoprevention of OM. Oral tissue preservation was better at lower temperatures (Study I). Proinflammatory cytokines were significantly upregulated (Study II). Several promising results were obtained with the intraoral cooling device (Study III). Local cooling may elicit other mechanisms in the oral mucosa than previously suggested that may be of importance for the prevention of OM (Study IV). A research protocol, to assess cryoprevention of OM, should be established through multidisciplinary collaborations and should include both objective- and subjective assessments (Study V). In conclusion, this thesis is the first to focus on the prevention of OM using an alternative cryotherapeutic technique. The work is mainly concerned with preclinical studies to identify the ideal temperature for the prevention of OM. Furthermore, this thesis demonstrates the tolerability and cooling efficacy of the intraoral cooling device and shows that cooling may elicit other mechanisms in the oral mucosa than previously suggested. However, despite its promising capacity, the randomized controlled trial will elucidate the definite role of the intraoral cooling device in cryoprevention.
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| 7. |
- Bazargani, Farhan, 1969
(författare)
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Acute inflammation in peritoneal dialysis. Experimental studies in rats. Characterization of regulatory mechanisms.
- 2005
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Ingår i: Swedish Dental Journal. Supplement. - Göteborg : Göteborg University. - 0348-6672. ; 171, s. 1-57
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The predominant problems associated with peritoneal dialysis (PD) are ultrafiltration failure and peritonitis. PD maintains a state of intraperitoneal inflammation that affects the structure and function of the peritoneal membrane, potentially impairing ultrafiltration efficiency. Paradoxically, some PD fluids also have anti-inflammatory properties that may compromise the immune defense against peritonitis. This anti-inflammatory feature is mostly due to the glucose degradation products (GDPs), formed during heat-sterilization and storage of PD fluids. The main purpose of the present thesis was to study regulatory mechanisms behind the acute intraperitoneal inflammatory response in PD in the presence and absence of experimental peritonitis. Rats were exposed to a single dose of heat- or filter sterilized PD fluids either as an i.p. injection or as an infusion through an indwelling catheter, with or without supplementations, or pretreatment of the animals. The dwell fluid was analyzed zero, two and four hours later concerning activation of the complement and coagulation cascades, neutrophil recruitment and respiratory burst, ultrafiltration volumes, cytokine-induced neutrophil chemoattractant (CINC-1), rat mast cell protease 2 (RMCP-2), glucose, urea and histamine concentrations and ex vivo/in vitro intraperitoneal chemotactic activity.Exposure to filter sterilized PD fluid alone induced intraperitoneal complement activation and coagulation, neutrophil recruitment and increased the levels of CINC-1 during the dwell. Intraperitoneal concentrations of the mast cell markers histamine and RMCP-2 changed little during the dwells and did not indicate mast cell activation. Low molecular weight heparin (LMWH) and C5 blockade improved ultrafiltration. Pretreatment with cobra venom factor, known decomplementing agent, blocked the CINC-1 release and the neutrophil recruitment and improved ultrafiltration. In combination with experimental peritonitis, heat sterilized PD fluid compared to filter sterilized, inhibited the CINC-1 release and the recruitment of neutrophils to the peritoneal cavity without affecting the intraperitoneal complement activation.The results of the present thesis indicate that addition of LMWH to the PD fluid improves ultrafiltration, probably by blocking C5a activity. C5 blockade seems to improve ultrafiltration by a mechanism that involves a reduction in glucose transport, possibly by reducing C5 induced vasodilation. Complement activation is an early step in the acute reaction to PD and probably mediates the downstream events that lead to the recruitment of inflammatory cells to the peritoneal cavity. The cells involved in the release of CINC-1 later in this sequence are probably the mesothelial cells. During experimental peritonitis, heat sterilized PD fluids inhibited the neutrophil respiratory burst response of intraperitoneal neutrophils. Heat sterilized PD fluids also inhibit the recruitment of neutrophils to the peritoneal cavity by a mechanism independent of complement activation but probably depending on cytokine CINC-1 release during peritonitis.
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| 10. |
- Johansson, Gunvi, 1950-
(författare)
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On Oral Health-Related Quality of Life in Swedish Young Adults
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Young adults in Sweden have grown up with dental care free of charge until the age of twenty. Their self-perceived oral health has been reported as being good, but rapid changes in society have led to a weaker economic situation for many young adults, which may influence their dental attendance and priorities concerning oral health and oral health care. The overall aim of this thesis was to explore the views of young adults on dental care, oral health and Oral Health-Related Quality of Life (OHRQoL).The thesis is based on four scientific papers which all apply a qualitative approach. In Paper I, the views of young adults on dental care were explored. Paper II investigated the views of young adults on their oral health and OHRQoL. In Paper III, measures of OHRQoL were described and analysed from a public health perspective, and in Paper IV, the views of young adults on the relevance of three measures of OHRQoL were explored. In Paper I, II, and IV, data collection was performed through qualitative interviews. The selection of informants was strategic with reference to age (21-29 years), sex and education. For Paper III, a literature search for OHRQoL measures was made in the PubMed database. The data in Paper I was analysed in accordance with the constant comparative method (inspired by Grounded Theory), and in Papers II, III and IV, qualitative content analysis was used.The results showed that young adults were satisfied with the dental care that they had received but reported specific views and demands on dental care (Paper I). They perceived their oral health as good, but an array of oral health problems was described (Paper II). The young adults’ perceived control of their OHRQoL depended on their future prospects of oral health, in relation to their perceptions of their past and present oral health. In Paper III, the search for measures of OHRQoL in the PubMed database generated 22 measures. The measures were analysed with regard to their theoretical framework and in relation to four principles of health promotion. Some elements of public health principles were found in all the measures, but most of them originated in disease-oriented theories. The occurrence of oral problems was reflected in young adults’ views on the measures of OHRQoL (Paper IV). The analysed measures were deemed to have both advantages and disadvantages but to be fairly equal.The conclusions are that young adults’ OHRQoL was dependent on their earlier experiences of dental care and their former and present oral health, as well as their future prospects regarding oral health. Elements of public health principles were present to a varying degree in all the measures of OHRQoL. Young adults regarded the frequently used measures of OHRQoL as being equal. The measures were mainly disease-oriented and no specific measures had been developed for young adults.
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