| 1. |
- Scheer, Vendela, 1967-, et al.
(author)
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The pencil eraser swab technique to quantify Cutibacterium acnes on shoulder skin
- 2021
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In: Journal of Bone and Joint Infection. - Göttingen, Germany : Copernicus publications. - 2206-3552. ; 6:9, s. 451-456
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Journal article (peer-reviewed)abstract
- Introduction: Cutibacterium acnes is the most common cause of postoperative infections in orthopaedic shoulder surgery and is hard to eradicate with current measures. Newer strategies focus on reducing bacterial load on the skin before surgery. Several previous studies have used a large number of both described and undescribed sampling techniques. The purpose of this study was to compare three previously described swab techniques to obtain bacterial cultures: Levine's (L) technique, the Z technique and the pencil eraser swab (PES) technique. Methods: Three consecutive skin swabs were collected from the right shoulder, on 15 healthy male volunteers, using Levine's technique, Z technique and PES technique from each participant. To determine the number of living bacteria, serial dilutions were made, and after culturing for 5 d, viable count (VC) was expressed as CFU/mL (with CFU representing colony-forming unit). Results: The PES technique yielded significantly higher VC than the two others. PES: median 3700 CFU/mL, L: 200 CFU/mL and Z: 220 CFU/mL ( p=0.003). There was no significant difference between the methods regarding the number of positive cultures. PES: 14/15, L: 11/15 and Z: 12/15. Conclusions: There is a need to harmonise sampling techniques of C. acnes in order to compare the efficacy of different measures to reduce the bacterial load on the skin before and during surgery. Of the three tested methods, the PES technique is simple and produces the highest bacterial counts.
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| 2. |
- Scheer, Vendela, 1967-
(author)
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Perioperative Strategies to Prevent Surgical Site Infection After Shoulder Surgery
- 2022
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Doctoral thesis (other academic/artistic)abstract
- In Sweden, about 18 000 patients undergo shoulder surgery each year. The current surgical site infection (SSI) rate after planned shoulder surgery is 0,3-5 %, which means that approximately 300 people are affected each year in Sweden. Treatment of deep SSIs always involves at least one reoperation followed by long-lasting treatment with antibiotics. In addition to pain and reduced mobility, an SSI can also have a negative effect on mental health. It is not possible to pinpoint exactly what causes an SSI. However, in today´s modern operating theatres with ultra clean air, tightly woven gowns, and surgical practice that strictly adheres to aseptic guidelines, SSIs after orthopaedic surgery are predominately caused by bacteria from the patient’s skin.The aim of this thesis was to evaluate perioperative strategies to prevent surgical site infection after shoulder surgery, focusing on bacterial burden on the skin. Cutibacterium acnes (C. acnes), a skin commensal, thrives in the sebaceous glands and causes most infections after shoulder surgery. Despite strict standardised preoperative preparation with 0.5% chlorhexidine solution in 70% ethanol, studies have shown that C. acnes are only partially eradicated. Topical treatment with benzoyl peroxide (BPO) over several months has been used to treat acne vulgaris for more than 50 years.In two randomised studies, we compared prophylactic topical treatment with BPO (applied five times over a period of 48 hours before surgery), with a control group with no BPO treatment. In the BPO group, the burden of C. acnes prior to incision and at the end of the surgery decreased significantly.When studying the effects of skin preparation, the technique and method used to capture the microbiome while maintaining the skin’s barrier, is crucial. In a pilot study, we developed a novel Pencil Eraser Swab-technique (PES) and compared this with two established swab techniques. The PES-technique was found to be significantly better, both in terms of sensitivity in detecting C. acnes and in quantification of viable bacteria.Following closure of a surgical incision, the wound is re-epithelialised within 24-72 hours. Choice of dressing is usually a question of personal preference and tradition rather than evidence based. The degree of colonisation of bacteria beneath wound dressings with different occlusive properties is not known. To investigate this, we compared three wound dressings of varying permeability on healthy skin. After 48 hours we found that recolonisation of bacteria was significantly higher beneath the semipermeable and occlusive wound dressings, than beneath the airy (gauze) dressing.Perioperative reduction of the bacterial burden on the skin is important in the fight against surgical site infection. A reliable technique to capture bacteria is essential when evaluating different methods.
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| 3. |
- Bergman-Jungeström, Malin, 1967-, et al.
(author)
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Association between CYP17 gene polymorphism and risk of breast cancer in young women
- 1999
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 84, s. 350-353
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Journal article (peer-reviewed)abstract
- Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T→C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1–3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1.9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41–1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women.
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| 4. |
- Bergman-Jungeström, Malin, 1967-, et al.
(author)
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Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women
- 2001
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 85:6, s. 859-862
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Journal article (peer-reviewed)abstract
- Oestrogen exposure has long been considered to be a main risk factor of breast cancer. More recently, interest has also focused on the possible carcinogenic influence from oestrogen metabolites, such as catechol oestrogens. O-methylation, catalysed by Catechol-O-Methyltransferase (COMT), is one pathway by which the potentially carcinogenic catechol oestrogens can be inactivated. The gene coding for COMT protein contains a single-nucleotide polymorphism (SNP), resulting in an amino acid shift Val Met, which has been shown to determine high- and low-activity configuration of the enzyme. We hypothesized that the low-activity allele, COMTMet, may be implicated in early onset breast cancer. In the present case–control study, including 126 young breast cancer patients ( 36 years) and 117 healthy female blood donors, we analysed the association between COMTMet genotype and risk of breast cancer. No significant difference in the frequency of low-/high-activity alleles was found between cases and controls, indicating that the polymorphism, as a single factor, may not contribute to breast carcinogenesis in young women.
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| 5. |
- Bergman, Malin, 1967-, et al.
(author)
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Flaxseed and its lignans inhibit estradiol-induced growth, angiogenesis, and secretion of vascular endothelial growth factor in human breast cancer xenografts in vivo
- 2007
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:3, s. 1061-1067
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Journal article (peer-reviewed)abstract
- Purpose: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, which is crucial in cancer progression. We have previously shown that estradiol (E2) increases VEGF in breast cancer. Phytoestrogens are potential compounds in breast cancer prevention and treatment by poorly understood mechanisms. The main phytoestrogens in Western diet are lignans, and flaxseed is a rich source of the mammalian lignans enterodiol and enterolactone.Experimental Design: In the present study, ovariectomized mice were treated with continuous release of E2. MCF-7 tumors were established and mice were fed with basal diet or 10% flaxseed, and two groups that were fed basal diet received daily injections with enterodiol or enterolactone (15 mg/kg body weight).Results: We show that flaxseed, enterodiol, and enterolactone counteracted E2-induced growth and angiogenesis in solid tumors. Extracellular VEGF in vivo, sampled using microdialysis, in all intervention groups was significantly decreased compared with tumors in the basal diet group. Our in vivo findings were confirmed in vitro. By adding enterodiol or enterolactone, E2-induced VEGF secretion in MCF-7 cells decreased significantly without agonistic effects. The increased VEGF secretion by E2 in MCF-7 cells increased the expression of VEGF receptor-2 in umbilical vein endothelial cells, suggesting a proangiogenic effect by E2 by two different mechanisms, both of which were inhibited by the addition of lignans.Conclusions: Our results suggest that flaxseed and its lignans have potent antiestrogenic effects on estrogen receptor-positive breast cancer and may prove to be beneficial in breast cancer prevention strategies in the future.
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| 6. |
- Bergman, Malin, 1967-
(author)
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Genetic polymorphism and breast cancer risk in young women
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Breast cancer is the most common malignancy among women in the western world. Although the disease is rare in young women, it is one of the main causes of death at young age. The early onset breast cancer has demonstrated more aggressive pathological features than the late onset disease. These observations have raised the hypothesis that the biological background may differ between age categories.Breast carcinogenesis is a micro-evolutionary process that requires accumulation of DNA-damage and other epigenetic changes that promote cell survival and proliferation. The complexity of the disease makes it difficult to identify specific risk factors. Nevertheless, a large and compelling body of epidemiological and experimental data suggests that the cumulative dose of oestrogen is one key factor in the aetiology. Also, substantial data indicates that oxidative stress, from phosphorylation or other metabolic processes, is involved in the development of breast cancer. In young women, there is a strong genetic influence of breast cancer risk and beside mutations in highly penetrant genes, polymorphisms in a number of crucial genes may modify an individual's risk. Such modifier genes, associated with a more modest risk and high prevalence in the population, may contribute to a large proportion of the disease in the population. Identification of such predisposing polymorphisms may be an important step forward in identifiying individuals at risk. In the present thesis genetic polymorphisms in four different genes and their relation to early onset breast cancer, were analysed.In the first study, a polymorphism with a TaqI restriction site in the vitamin D3 receptor (VDR) gene was studied. VDR and its ligand, 1,25(OH)2D3, have been suggested to be important factors for differentiation of the breast epithelium and may suppress mammary tumorigenesis. The presence of a TaqI restriction site has been shown to correlate with increased transcriptional activity and mRNA stability of VDR, as well as high serum levels of 1,25(OH)2D3 and this high receptor activity may be protective against breast cancer. In the present study VDR TaqI polymorphism did not predict risk of early onset breast cancer. However, the results indicate an association between lymph node metastasis and genotype. In the second study, a promoter polymorphism in the CYP17 gene, which may influence the oestrogen synthesis, has been analysed. The polymorphism was correlated to the risk of early onset breast cancer, and the risk increased in a dose dependent manner. The fmdings indicated also a trend for risk allele carriers to have ER-negative and large tumours. Oestrogens are metabolized to potentially carcinogenic catecholoestrogens, which could be inactivated by and O-methylation, catalysed by Catechol-O-methyltransferase (COMT). This gene contains a variant which encode for a protein with decreased activity and is therefore predicted to be a risk allele. In the third study, the investigation of allele frequencies of the polymorphic COMT gene did not show any epidemiological evidences of implication in breast cancer. Finally; increasing numbers of studies indicate an important role for MnSOD in a number of cancer cell types. A genetic variant of MnSOD results in a less efficient transport into the mitochondria which may lead to an insufficient scavenging of free radicals. In this study, the mitochondrial targeting polymorphism was associated with risk of breast cancer in young women.In conclusion, genetic polymorphism in crucial genes may have impact on the risk of early onset breast cancer. Furthermore, some genotypes seems to influences the progression and outcome of the disease.
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| 7. |
- Bergman, Malin, 1967-, et al.
(author)
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Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women
- 2005
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In: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 131:7, s. 439-444
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Journal article (peer-reviewed)abstract
- Purpose: Manganese superoxide dismutase (MnSOD) is one of the major enzymes implicated in the cellular defence against reactive oxygen species. Low expression of MnSOD has been observed in different cancer tissues and several reports have shown that overexpression of MnSOD inhibits growth in various human cancer cells. These observations suggest that MnSOD is involved in carcinogenesis. A polymorphism (Ala-9Val) in the mitochondrial targeting sequence (MTS) of the MnSOD gene has been proposed to affect protein localization and thereby influence cellular defence against superoxide radicals.Methods: In the present case-control study, including 118 early onset breast cancer patients (≤36 years) and 174 age-matched controls, the MTS polymorphism and loss of heterozygosity (LOH) in the locus of MnSOD were analysed.Results: We found that individuals with MnSODVal/Val and MnSODVal/Ala genotypes showed an increased risk of breast cancer (OR, 2.7; 95% CI, 2.2–5.5, p=0.01, OR, 3.0; 95%CI, 1.4–6.5, p=0.002). Moreover, 45% of the informative cases expressed allelic loss at the chromosomal locus of the MnSOD gene. No correlation was found between LOH and the genotype.Conclusion: The present study suggests that MnSOD may be implicated in breast carcinogenesis in young women.
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| 8. |
- Gentile, Massimiliano, et al.
(author)
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p53 and survival in early onset breast cancer : analysis of gene mutations, loss of heterozygosity and protein accumulation
- 1999
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In: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 35:8, s. 1202-1207
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Journal article (peer-reviewed)abstract
- The p53 protein has proven to be central in tumorigenesis by its cell cycle regulatory properties and both gene mutations and protein accumulation have been associated with poor prognosis in breast cancer. The present study was undertaken to investigate the prognostic significance of gene mutations, p53 protein accumulation and of loss of heterozygosity (LOH) at the TP53 locus in young (age <37 years) breast cancer patients. In total, gene mutations were found in 21 of the 123 patients (17%), LOH in 20 of the 47 informative cases (43%) and protein accumulation in 47 of the 102 available cases (46%). Log rank analysis revealed no significant association between survival and TP53 mutations (in general), p53 protein accumulation or LOH. However, missense mutations localised to the zinc binding domain were significantly (P=0.0007) associated with poorer prognosis. As indicated in this as well as other studies, p53 protein accumulation is frequently found in young breast cancer patients, but this protein overexpression appears to be of minor significance for survival. Nevertheless, the present report also suggests that specific mutations contribute substantially to tumour aggressiveness.
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| 9. |
- Jerevall, Piiha-Lotta, 1980-, et al.
(author)
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Sulfotransferase1A1 and risk of postmenopausal breast cancer
- 2005
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 25:3 C, s. 2515-2517
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Journal article (peer-reviewed)abstract
- The detoxification enzyme sulfotransferase1A1 (SULT1A1) is implicated in the inactivation of estrogens and the activation of promutagens andprocarcinogens. SULT1A1 activity varies among individuals, and this difference in phenotype is, in part, controlled by genetic polymorphism (Arg→His in codon 213). It is hypothesized that the His allele contributes to the risk of postmenopausal breast cancer. Frequencies of the Arg/His alleles were estimated in 229 postmenopausal breast cancer patients and 227 age-matched controls using a PCR-RFLP assay. Allele frequencies and genotype distributions were not statistically different between postmenopausal breast cancer patients and the population-based controls, i.e. neither of the alleles is associated with an increased risk of breast cancer in the present study.
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| 10. |
- Lundin, Anna-Carin, et al.
(author)
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Association of breast cancer progression with a vitamin D receptor gene polymorphism
- 1999
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 59:10, s. 2332-2334
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Journal article (peer-reviewed)abstract
- The vitamin D3 receptor gene (VDR) contains a TaqI RFLP that is associated with increased VDR mRNA stability, increased serum levels of 1α,25-dihydroxyvitamin D3 (1,25-D3), and decreased risk for prostate cancer. Determination of the TaqI genotype, in a group of young women with breast cancer (n = 111; age, <37 years) and a control population (n = 130), revealed no overall association to risk for breast cancer. However, patients without TaqI site (TT genotype) showed a significantly increased risk for lymph node metastasis (relative risk, 1.8, 95% confidence interval, 1.3- 2.6). Furthermore, a tendency toward an increased survival was found among estrogen receptor-positive, tamoxifen-treated patients who were homozygous for the TaqI site (P = 0.075). We conclude that polymorphism in the VDR gene may influence tumor progression and tamoxifen treatment response in early- onset breast carcinomas.
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