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Aim We evaluated the role of placental pathology in predicting adverse outcomes for neonates born extremely preterm (EPT) before 28 weeks of gestation. Methods This was a prospective observational study of 123 extremely preterm singletons born in a hospital in western Norway, and the placentas were classified according to the Amsterdam criteria. The associations between histologic chorioamnionitis (HCA), by the presence or the absence of a foetal inflammatory response (FIR+ or FIR−), maternal vascular malperfusion (MVM) as a whole and adverse neonatal outcomes were evaluated by logistic regression analyses. Adverse outcomes were defined as perinatal death, necrotising enterocolitis (NEC), bronchopulmonary dysplasia (BPD), brain pathology by magnetic resonance imaging at term-equivalent age, retinopathy of prematurity and early-onset neonatal sepsis. The results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results HCA was associated with NEC (OR 12.2, 95% CI 1.1 to 137.1). HCA/FIR+ was associated with BPD (OR 14.9, 95% CI 1.8–122.3) and brain pathology (OR 9.8, 95% CI 1.4–71.6), but HCA/FIR− was not. The only neonatal outcome that MVM was associated with was low birthweight. Conclusion Placental histology provided important information when assessing the risk of adverse neonatal outcomes following EPT birth. publishedVersion

Purpose: To report intra- and postoperative surgical outcome using the bag-in-the-lens (BIL) technique in paediatric cataract surgery. Methods: In a retrospective case series, we studied the outcomes of children aged

PURPOSE To evaluate the results of surgical treatment in a large group of patients with trochlear nerve palsy, with emphasis on the self-grading effect of a standardized recession of the ipsilateral inferior oblique muscle. METHODS All patients who underwent first-time surgery for trochlear nerve palsy in the period 2005-2014 in our department (n = 114) were retrospectively evaluated regarding pre- and postoperative data, surgical procedure, and the need for reoperations. Mean follow-up time was 8.5 ± 13.8 months. RESULTS Among the 114 patients, 73 (64.0%) had a congenital palsy, 31 (27.2%) an acquired palsy, while in 10 cases (8.8%) the type of palsy was uncertain. A standardized recession of the ipsilateral inferior oblique muscle with reattachment at the lateral border of the inferior rectus muscle was carried out in 97.3% of the congenital palsies and in 80.5% of the acquired/uncertain group. In the total patient material, further surgery was needed in 15.8%. Among the patients who underwent a single standardized recession of the inferior oblique muscle, a significant correlation between preoperative vertical angle of deviation and the postoperative change in deviation was demonstrated (correlation coefficient -0.70, p

Purpose Androgen receptor (AR) expression is frequent in breast cancer and has been associated with good prognosis in several studies. The present study investigates AR-expression in relation to molecular subtypes, clinicopathological features and prognosis in 1297 primary tumours and 336 paired axillary lymph node metastases (LNM) from two cohorts of Norwegian patients. Methods Immunohistochemistry for AR was performed on tumours previously reclassified into molecular subtypes using immunohistochemistry and in situ hybridisation. Associations between AR-expression and clinical features were studied using Chi-square tests. Cumulative incidence of breast cancer death and Cox regression analyses were used to assess prognosis. Results AR-positivity was found in 78.0% of all cases, 84.9% of luminal and 45.1% of non-luminal tumours. The highest proportion of AR-positivity was found in Luminal B tumours, and the lowest in the Basal phenotype. Discordance in AR-status between primary tumours and lymph node metastases was observed in 21.4% of cases. A switch from AR− primary tumour to AR+ lymph node metastasis was seen in 60/72 discrepant cases. AR-expression in primary tumours was an independent and favourable prognostic marker (HR 0.70, 95% CI 0.55–0.90), particularly in the Luminal A subtype, and in grade 3 tumours. Conclusions AR is an independent predictor of good prognosis in BC, particularly in grade 3 and Luminal A tumours. Discordant AR-expression between primary tumour and LNM was observed in 21.4% of cases and most often there was a switch from AR− primary tumour to AR+ axillary LNM. This is a post-peer-review, pre-copyedit version of an article published in [Breast Cancer Research and Treatment] Locked until 14.8.2019 due to copyright restrictions. The final authenticated version is available online at: https://doi.org/10.1007/s10549-018-4904-x

Purpose: To determine ocular refraction, corneal thickness, corneal radius, corneal power, corneal astigmatism and intraocular pressure in patients before and immediately after repeated hyperbaric oxygen (HBO2) exposures twice a week during six weeks of HBO2 therapy. Methods: 23 patients received HBO2 therapy at 2.4 ATA for 90 minutes daily in monoplace chambers for six weeks, five days a week. The Topcon TRK-1P instrument was installed next to the hyperbaric chambers to record the ocular measurements. Results: A gross myopic shift developed at -0.95 ± 0.54 D (P < 0.001) in the right eye and -0.95 ± 0.53 D (P < 0.001) in the left eye during the six weeks of treatment. Myopic shift reversion, corneal thinning and reduced intraocular pressure appeared as immediate effects after a single HBO2 exposure, but resolved before the patients attended for the next measurement visit. Conclusions: Ocular variables were influenced by both cumulative and transient short-term effects during the HBO2 therapy. The short-term effects showed that the point of time for performing the ocular measurements after HBO2 exposure might influence the result and must be considered before making relevant comparisons among studies.

We present a case of a young female with a slowly progressing visual impairment who was examined with multifocal visual evoked potentials and functional magnetic resonance imaging (fMRI) for underlying neuronal abnormality. The fMRI examination consisted of presenting black-and-white checkerboard stimuli, and her activation patterns were compared to the patterns from 4 normal-sighted subjects. The results showed clear differences in neuronal activation between the patient and the controls in the occipital and parietal lobes. Although we have shown neuronal correlates in a case of unexplained visual loss, it is still an open question as to whether this has an organic or functional cause, which should be the subject for future research.

Purpose To evaluate the outcome and late postoperative complications after lateral orbital wall decompression in a series of patients with thyroid eye disease (TED). Methods One hundred and three patients operated in the period 1999–2013 were invited to participate in the study, and 84 were included after a median (range) follow-up time of 124 (13–188) months. The patients were interviewed, and preoperative and postoperative data were collected from hospital records. Photographs (‘selfies’) were obtained from 64 patients. Wilcoxon signed-rank test was used to evaluate the change in pre- and postoperative data. Results On average, visual acuity was unchanged with a median value (range) of 1.0 (0.4–1.25) before to 1.0 (0–1.25) after surgery (p = 0.5). Intraocular pressure (IOP) was reduced from a median value (range) of 17 (9–26) to 15 (8–23) mmHg (p

BACKGROUND Due to failures in reporting and poor data security, the Norwegian Registry of Blindness was closed down in 1995. Since that time, no registration of visual impairment has taken place in Norway. All the other Nordic countries have registries for children and adolescents with visual impairment. The purpose of this study was to survey visual impairments and their causes in children and adolescents, and to assess the need for an ophthalmic registry.MATERIAL AND METHOD Data were collected via the county teaching centres for the visually impaired in the period from 2005 - 2010 on children and adolescents aged less than 20 years with impaired vision (n = 628). This was conducted as a point prevalence study as of 1 January 2004. Visual function, ophthalmological diagnosis, systemic diagnosis and additional functional impairments were recorded.RESULTS Approximately two-thirds of children and adolescents with visual impairment had reduced vision, while one-third were blind. The three largest diagnostic groups were neuro-ophthalmic diseases (37 %), retinal diseases (19 %) and conditions affecting the eyeball in general (14 %). The prevalence of additional functional impairments was high, at 53 %, most often in the form of motor problems or cognitive impairments.INTERPRETATION The results of the study correspond well with similar investigations in the other Nordic countries. Our study shows that the registries associated with teaching for the visually impaired are inadequate in terms of medical data, and this underlines the need for an ophthalmic registry of children and adolescents with visual impairment. Language: no

Published article Aims The aim of this study was to compare breast cancer specific survival (BCSS) for invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and, further, to evaluate critically the prognostic value of histopathological grading of ILC and examine E-cadherin as a prognostic marker in ILC. Methods and results The study comprised 116 lobular and 611 ductal breast carcinomas occurring between 1961 and 2008. All cases had been classified previously according to histopathological type and grade, stained for oestrogen receptor (ER), progesterone receptor (PR), antigen Ki67 (Ki67), epithelial growth factor receptor (EGFR), cytokeratin 5 (CK5) and human epidermal growth factor receptor 2 (HER2) and classified into molecular subtypes. For the present study, immunohistochemical staining for E-cadherin was performed. The Kaplan–Meier method and Cox proportional hazards models were used in the analyses. Grade 2 tumours comprised 85.3% of the lobular tumours and 51.9% of the ductal tumours. BCSS in ILC grade 2 was comparable to that of IDC grade 3. E-cadherin-negative ILC had a poorer prognosis compared to E-cadherin positive ILC and to IDC regardless of E-cadherin status. Conclusions The implication of histopathological grading may differ in ILC compared to IDC. E-cadherin may be useful in prognostication in ILC and thereby influence the determination of treatment strategies for this group of women This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made

Purpose To evaluate the outcome of endoscopic decompression in a series of patients with thyroid eye disease. Methods All 46 patients operated at our institution in the period 2001 to 2011 were invited for re-examination. Thirty-seven patients were included in the study and underwent a general otorhinolaryngological and ophthalmological examination. Nasal endoscopy, autoperimetry and a CT scan of the orbits and paranasal sinuses were performed. Preoperative and early postoperative data were obtained from hospital records. Re-examination was performed from 12 months to 9 years postoperatively. Paired t-test was used to evaluate the change in pre- and postoperative data. Image-guided surgery was used in two patients. Results Visual acuity improved from a median value (range) of 0.8 (0.05–1.25) to 1.0 (0.4–1.25) (p = 0.006). Intra-ocular pressure (IOP) was reduced from a median value (range) of 18 mmHg (10–27 mmHg) to 14 mmHg (8–24 mmHg) (p

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2-)], Luminal B (HER2+), HER2 subtype, basal-like phenotype (BP) and five-negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend , 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend , 0.002), Luminal B (HER2-) (ptrend , 0.02), Luminal B (HER2+) (ptrend , 0.06), and also for the HER2 subtype (ptrend , 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.

We describe an adolescent Peruvian male with marked, aggressive ingrowth of conjunctiva (pterygium-like) over the cornea associated with keloid formation on his distal limbs. He has in addition camptodactyly of all fingers and to some extent of his toes, and unusual skin pigmentations. He resembles an earlier described family from Norway in which a mother and two children showed a similar combination of signs. We present the follow-up of the Norwegian family. The entity resembles the Penttinen syndrome but can be differentiated due to the early aging in the latter, which is lacking in the presently reported entity. We suggest naming this entity ocular pterygium-digital keloid dysplasia. The condition follows likely an autosomal dominant pattern of inheritance.

Background: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886–1977. Methods: A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886–1928 and 1929–1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs. Results: Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2−) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50–54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8–6.9 and 2.5; 95% CI, 1.2–5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3–0.5), Luminal B (HER2−; HR 0.5; 95% CI, 0.3–0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2–0.9). Conclusions: We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2−) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype. Impact: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625–34. ©2016 AACR.

Purpose. To examine the optical components of phakic and pseudophakic eyes during hyperbaric oxygen (HBO) therapy, and to quantify their relative impact on ocular refractive changes. Methods. HBO therapy was given to 16 phakic and six pseudophakic patients for 90 min daily at a pressure of 240 kPa, 5 d a week for 20 days. An eye examination was performed on the first day of HBO therapy and repeated when the patients had completed 19 days of the treatment. Refractive error, best-corrected visual acuity, corneal power, radius, thickness and volume, anterior chamber depth, axial length, lens opacity, and intraocular pressure were measured in all patients. Serum glucose, glycosylated hemoglobin, serum electrolytes, and protein were measured in the phakic patients. Results. In the phakic group, a significant myopic shift (0.50 D) occurred in 26 (81%) single eyes during the treatment. The median myopic shift was 0.63 D (min 0.25 D/max 1.88 D) in the OD, and 0.69 D (min 0.38 D/max 2.25 D) in the OS. No myopic shift appeared in the pseudophakic patients; the median refractive changes were 0.06 D (min 0.13 D/max 0.25 D) in the OD and 0.13 D (min 0.00 D/max 0.25 D) in the OS. Intraocular pressure, serum electrolytes, glucose, and glycosylated hemoglobin remained unchanged. Conclusions. Myopic shifts occurred in phakic but not in pseudophakic eyes during HBO therapy. The myopic shifts must be attributed to changes in the crystalline lens. (Optom Vis Sci 2011;88:1–●●●)

The distribution of cell types in the pituitary gland was studied in a consecutive autopsy series of men over 40 years of age. Among 166 individuals, not previously subjected to prostatic surgery or oestrogen treatment, the proportion of PAS-positive cells was higher in men with hyperplasia or neoplasia of the prostate than among individuals showing a histologically normal prostate. PAS-positive cell counts were negatively influenced by several factors related to wasting disease, while acidophil cells apparently increased in conditions of acute and severe stress. Using multiple regression analysis, benign prostatic hyperplasia was selected as the only one among histological diagnoses which significantly reduced the variability of PAS-positive cell proportion, even when the negative influence of other factors had been accounted for. PAS-positive cell counts did not effectively discriminate between the various forms of abnormal prostatic growth encountered. The data presented indirectly give support to the concept of some form of endocrine derangement in the ageing male.

Eighty patients with senile cataract were subjected to a planned extracapsular cataract extraction (ECCE) with implantation of a posterior chamber intraocular lens. Retrobulbar anesthesia was administered by injection of 4 mg lidocaine 2% with adrenalin. In 40 patients 150 I.U. hyaluronidase (Kinetin®) was added to the anesthesia. The hyaluronidase group had a significantly lower frequency of iris prolapse, and deeper anterior chamber, both before and after expression of the lens nucleus. Possible mechanisms explaining the beneficial effect of hyaluronidase in extracapsular cataract surgery are discussed.

Epikeratophakia for keratoconus was done in 11 mentally retarded patients, using fresh, free-hand made lamellar grafts. The mean follow-up period was 31.5 months. The grafts remained clear and well adapted in 7 cases (63.6%). Necrosis of the lower part of the graft occurred in 3 eyes (27.3%), and was probably caused by persisting epithelial defects. Only one of these grafts had to be removed. Despite concurrent eye diseases, such as cataract and possible amblyopia, an improved overall visual function was reported in 5 of the 11 patients (45.5%). No vision-threatening complications related to the epikeratophakia surgery was found.

Background and Objective Bruises are currently evaluated by visual inspection, and little is known about the first phase after injury. The temporal development of fresh injuries must be accurately described to be able to age bruises in a reliable manner. Color changes in a bruise caused by hemoglobin breakdown products will depend on the severity of the trauma, and thus on the local immune response in the skin. It is therefore important to relate the nature of the impact to the temporal tissue responses. Materials and Methods Controlled injuries were inflicted on anesthetized domestic pigs. Trauma was induced either by a pendulum device, or by paintballs released using pressurized air. The speed of the projectiles was recorded using a high speed camera. Biopsies and reflection spectra (400–850 nm) were collected from normal and bruised skin. The experiments were approved by the national animal research authority. Results The temporal development of the injury was found to depend strongly on the weight and speed of the object. Low speed, blunt objects did not cause persistent skin changes. However, deep muscular bleeding could be found in most cases. High speed, light weight objects caused a rapidly developing bruise. These bruises were fully developed within 15–20 minutes. No deep muscular hemorrhages were observed in those cases. White blood cells (neutrophilic granulocytes) could be found in biopsies from high speed injuries. The amount of white blood cells depended on the time between injury and collection of the biopsies. Conclusion Further investigations utilizing a larger range of object weight and velocities are required to be able to fully classify minor traumatic injuries. Preliminary results indicate that this can be achieved by controlled experiments using a porcine model. Reflectance spectroscopy was found to be a useful tool to study immediate skin reactions to the trauma. Lasers Surg. Med. © 2007 Wiley-Liss, Inc.

A 58-year-old man presented with a change in vision during hyperbaric oxygen (HBO) therapy. Subsequent follow-up visits showed a hypermetropic shift, which succeeded the myopic shift after each of two series of HBO treatments. The maximal refractive amplitude was 3.00 D (range -1.37 D to +1.62 D) in the right eye and 2.75 D (range -1.25 D to + 1.50 D) in the left eye. Refraction stabilized after 1.5 years at +0.62 D and +0.50 D to pretreatment values in the right and left eye, respectively. The findings are discussed with regard to possible changes in the structure of the lens.

Background and Objectives Aging of injuries on a victim's body is an important aspect of forensic medicine. Currently, visual assessment and colorimetry based on empirical criteria are the most common techniques for this task, although the results are uncertain. A trauma causing localized vessel damage will rapidly result in a pool of blood in subcutaneous tissues. The color of the bruise is, however, primarily due to hemoglobin transport into dermis and secondarily to its breakdown products. This transport is analyzed in terms of hemoglobin diffusion followed by clearance by macrophage activity, lymphatic flow, and conversion to breakdown products such as bilirubin. The color of a bruise is caused by hemoglobin and hemoglobin breakdown products. The color will change with time, and such color changes can be recorded using reflectance spectroscopy. The aim of this study was to develop a mathematical model to describe blood diffusion within bruised skin, and to use this method to retrieve the age of a bruise from measured skin reflectance. Study Design/Materials and Methods An analytic model was established to describe the development and fading of bruise color. The model, which is based on Darcy's law of convection flow and Fick's law of diffusion, describes the distribution of blood and hemoglobin breakdown products within a hematoma as a function of time after injury. The initial phase after injury is described by a convective extravascular blood flow in subcutaneous tissues, and further development of the bruise is described by diffusion and breakdown of whole erythrocytes and hemoglobin in dermis. Experimental data were used to verify the model. Reflection spectra in the 400–850 nm wavelength range were collected from normal and bruised skin using an integrating sphere setup. The subjects were adult patients admitted to the Department of cardiothoracic surgery, St. Olav's Hospital, Trondheim, Norway. The skin hematomas were caused by external trauma, cardiothoracic examinations, or surgery. Results Preliminary results show that measured and simulated skin reflectance agrees well. The model predicts the age of a hematoma with an accuracy of approximately 1 day. The accuracy of the method depends on precise information of skin thickness in the injured area. The quality of the estimates from the model will thus be enhanced if a reliable measure of skin thickness is collected concurrently with the reflection measurement. Conclusions The time development of a skin hematoma is described with good accuracy by the implemented model. The analytic method provides a theoretical basis for developing an apparatus to determine the age of injuries in forensic medicine. Lasers Surg. Med. 38:277–289, 2006. © 2006 Wiley-Liss, Inc.

Objective: To compare the frequencies of pelvic lymphocele formation after laparoscopic and open pelvic lymph node dissection in patients with prostate cancer. Material and Methods: A total of 132 patients operated on with pelvic lymph node dissection (PLND) underwent CT scanning of the abdomen and pelvis at a median of 29 days postoperatively. Open pelvic lymph node dissection (OPLND) was performed in 94 patients (71%) and 38 patients (29%) were operated on using a laparoscopic technique (LPLND). The frequency and size of pelvic lymphoceles were registered. Lymphoceles with a horizontal diameter of

Background. At the turn of 2007/2008, four Norwegian men died after ingestion of commercially available supposedly denatured ethanol. Material and methods. The four deaths are presented and discussed. Results. Methanol concentrations, consistent with lethal methanol poisoning, were detected in blood and urine for all four. The imbibed mixture was subsequently shown to contain a 70/30 mixture of methanol/ethanol. Interpretation. The events emphasize the importance of investigating methanol findings from deceased to identify the source, and that investigations are instigated promptly to prevent further exposure. Language: no

Image-guided localized proton MR spectroscopy (MRS) of normal breasts and breast tumors (ductal and undifferentiated carcinomas) was performed using a dedicated double breast coil. In vivo 1H MR spectra from 10 normal volunteers showed signals from water and lipids only, even in breasts with small contribution of fatty breast tissue. In the spectra from 6 of the 12 examined patients, an intense signal assigned to choline compounds was detected. The signal was also detected at lower levels in the remaining patients. This study shows that in vivo 1H MRI/MRS examinations of breast tumors can be performed within an examination time of 45 to 60 minutes. Signals from breast tumor metabolites may be detected using in vivo 1H MRS.

PURPOSE To report a previously undescribed hereditary conjunctivo-corneal dystrophic disease associated with keloid formation in a woman and her two sons. METHODS We have been able to follow the affected members of the family with clinical examinations over many years. In addition, they have been examined with chromosome analyses and X-ray examination of their hands. RESULTS The mother and the oldest son have both shown a very similar clinical development, with fibrovacular tissue gradually covering the cornea, leading to severe visual loss in both eyes. In the youngest boy, the condition started at a later age, and to date only one eye is affected. All three patients have developed keloid scars on their hands. CONCLUSION The described condition seems to represent a previously unreported, autosomal dominant inherited disease. A congenital defect in the cell differentiation of the limbus region is discussed as a possible pathogenesis.

Norway had until recently no organized screening programme for cervical cancer, but opportunistic screening was common. This study focuses on the effectiveness of treatment of pre-malignant cervical conditions (CIN III) on cervical-cancer incidence in the county of Sor-Trondelag in Norway, prior to the introduction of organized mass screening. The study is based on cervical-cancer incidence rates during the years 1965-92 and treatment data for CIN III. The expected number of cervical-cancer cases prevented due to early intervention was expressed in a regression model with 2 unknown parameters: the probability, p, of cancer development in case of CIN III, and the time lag, t, between treatment and when clinical cancer would otherwise have been diagnosed. The estimated probability that a patient treated for CIN III would have developed cervical cancer if not treated was found to be approximately 20%, and the mean time delay was around 16 years. In the last period of study (1988-92), the incidence was reduced by nearly 40% of what would have been expected without early intervention. Based on equal treatment rates as in 1990, parameter estimates were used to predict future incidence reduction. Maximum effectiveness will be achieved around the year 2005, with a nearly 70% reduction. Opportunistic screening and treatment of CIN III seems to have had considerable influence on cervical-cancer incidence. The costs, however, are substantial over-treatment, since our results indicate that 4 of 5 women treated for CIN III would not progress into the invasive state.

Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes. We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2−) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype. We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype. The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.

Tobacco smoking has been reported to be associated with increased risk of cardiovascular disease and cancer, particularly of the lungs. In spite of extensive research on the health effects of tobacco smoking, the substances in tobacco smoke exerting these negative health effects are not completely known. Nicotine is the substance giving the subjective pleasure of smoking as well as inducing addiction. For the first time we report the effect on the rat of long-term (two years) inhalation of nicotine. The rats breathed in a chamber with nicotine at a concentration giving twice the plasma concentration found in heavy smokers. Nicotine was given for 20 h a day, five days a week during a two-year period. We could not find any increase in mortality, in atherosclerosis or frequency of tumors in these rats compared with controls. Particularly, there was no microscopic or macroscopic lung tumors nor any increase in pulmonary neuroendocrine cells. Throughout the study, however, the body weight of the nicotine exposed rats was reduced as compared with controls. In conclusion, our study does not indicate any harmful effect of nicotine when given in its pure form by inhalation.

Publshed article Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2−); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan–Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade (c) The Author(s) 2013. This article is published with open access at Springerlink.com

The aim of the study was to compare the histological outcome of the cone specimens with the diagnoses of the preoperative biopsies, to assess the distribution of histological features consistent with human papillomavirus (HPV) infection and, finally, to analyse the impact of cellular HPV features on classification of cervical intraepithelial neoplasia (CIN). The study comprised a population of 317 women treated for CIN by laser conization during the period 1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their corresponding cones) were studied retrospectively for CIN classification and examined for morphological signs of HPV infection. For presentation of the results, we used a modified terminology for CIN. Low-grade (LG) CIN included borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN III. The blinded histopathological review revealed HG CIN both in the preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions were found in the preoperative biopsies and their corresponding cone specimens in 6% of the study population. HPV features were present in 65% of the preoperative biopsies, and were most prevalent in women under 29 years of age (p < 0.001). Thirteen percent of the total biopsy material was downgraded. The downgrading was most prevalent among original CIN II (p = 0.009) and HPV-negative biopsies (p < 0.001). This study demonstrates that CIN lesions are frequently associated with HPV features, which are significantly more prevalent in the youngest women. Concomitant HPV features do not influence the CIN classification.

Increases in signal intensity enhancement were measured in defined regions of interest (ROIs) to allow distinction between malignant and benign tumors with dynamic gadolinium-enhanced magnetic resonance (MR) mammography. Twenty patients with palpable breast lesions (15 malignant, five benign) underwent MR mammography. The dynamic gradient-echo sequence was performed with intravenous bolus injection of gadopentetate dimeglumine and consisted of 25 images with a time resolution of 30 seconds. Contrast enhancement was calculated by comparing user-defined ROIs on pre- and postcontrast images. An increase in signal intensity of 70% or more on the 1-minute postcontrast image was used as the criterion of malignancy. MR mammographic results correlated with histopathologic findings in all patients when the defined ROI was in the most enhancing part of the tumor. For the ROI in areas of submaximal enhancement or when the ROI surrounded the whole lesion, only five and nine tumors, respectively, fulfilled the malignancy criterion. All malignant tumors showed large variations in signal intensity enhancement that depended on the position of the ROI in the tumor. Dynamic, gadolinium-enhanced MR mammography allows distinction of benign from malignant breast tumors when the selected ROI is in the most enhancing part of the lesion.

The routine use of dilatation and curettage (D&C) is questioned as a standard procedure for endometrial sampling. Instruments have been developed in order to simplify the procedure. The aim of the present study was to estimate the sensitivity to detect malignancy/premalignancy by histological examination of endometrial samples obtained by microcurettage using a disposable plastic curette, Gynoscann. The histological examination of the combined microcurettage and D&C material was defined as the true diagnosis. All patients undergoing diagnostic D&C at the two participating hospitals were included in the study. The endometrial samples were evaluated at the Department of Pathology as part of their routine work. The microcurettage samples were re-examined independently by two pathologists (observer 1 and observer 2) who did not have access to the rest of the tissue material nor the diagnosis given previously. A total of 902 patients were enrolled in the study. Endometrial cancer was found in four women below 50 years of age. None of these were detected by histological examination of the Gynoscann obtained sample. Among women aged 50 and above, samples from 16 women turned out to have endometrial cancer. The microcurettage samples were correctly classified as malignant/premalignant by observer 1 in 13 cases and by observer 2 in 14 cases. We conclude that diagnostic D&C among women 50 years and below cannot be replaced by histological examination of Gynoscann samples without the risk of overlooking significant pathology.

Purpose: Progress in neonatal care has caused an increased survival of children born extremely preterm. The aims of this study were to examine the long-term visual function and ocular development in an unselected cohort of extremely preterm infants and relate the results to neonatal morbidity and long-term neurodevelopmental outcome. Methods: All children with gestational age of 22–27 completed weeks or birth weight of 500–999 g born in the years 1999–2000 in two counties of Western Norway (n = 52) were invited to an eye examination that included visual acuity, refractive error, binocular function, accommodative amplitude and fundus examination. Cognitive function was assessed with the WPSSI-R test and motor abilities with the ABC movement test. Results: Neonatal morbidities and neurodevelopmental outcome were known for all, while 37 of the 52 children underwent the eye examination. None were blind or visually impaired, but 46% had subnormal visual acuity (logMAR ‡0.1). Ninety per cent were emmetropic or slightly hypermetropic (0 to +3D), while 10% had manifest and 51% latent strabismus. Performance IQ on the WPSSI-R test and ABC total score were associated with best visual acuity (p = 0.03 and p < 0.01, respectively). In a multiple linear regression model, visual acuity in the best eye was significantly associated with performance IQ (p = 0.03) and ABC total score (p = 0.02). Conclusion: This study suggests a more favourable long-term prognosis on important ocular and visual parameters in survivors of extreme prematurity than expected from similar reports on children born less prematurely and that performance IQ and motor function are related to visual acuity.

Forensic medicine is a field of medicine where technology plays an increasingly important role in securing and evaluating evidence in, for example, child abuse cases and cases of domestic violence. Methods from chemistry and biological sciences have found a wide application within forensic medicine. Optical technologies like microscopy are also widely used. Despite this, in vivo or post mortem optical diagnostics by spectroscopy have traditionally not had an important role in clinical or forensic examinations. Forensic medical optics as a field might include all kinds of optical analysis for use within forensic science. This includes everything from microscopic techniques to methods for examination of evidence from a crime scene. This chapter will, however, focus on the use of optical diagnostics for examining skin, with a focus on identification, characterization and age determination of minor traumatic injuries like skin bruises.

The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated.Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study.Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66% (n = 41) and 22% (n = 12), respectively (p0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score ≥ 8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p0.0001.Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.

Imaging modalities like hyperspectral imaging create large amounts of data. Time efficient, automated analytic techniques are therefore required to enjoy the power of such methods. In this study it was investigated if hyperspectral imaging followed by automated noise filtering and statistical image analysis is a suitable method for characterization of the macroscopic structure of atherosclerotic lesions. Ten human aorta samples (6x8 cm) were collected during autopsy. Hyperspectral white light and fluorescence images and 5 – 6 biopsies were collected from each sample. The biopsies were stained (HES, Sudan red), and grouped according to histology. All images were noise filtered and normalized. Fluorescence spectra were collected from all biopsied regions, and used to compute average spectra for each histological group. Supervised classification was performed using Spectral angle mapping (SAM) with the average spectra as endmembers. K-means- and ISO-data clustering was used for unsupervised classification. The results show that noise filtering and normalization is essential for reliable classification. Supervised classification was in general found to perform better than unsupervised classification. However, the SAM results strongly depend on the variation in the spectra used to compute the average endmember spectra. The analysis show that fatty deposits, calcifications, connective tissue and hemoglobin can be identified. The lesions were found to have a complex structure where vulnerable regions could be found next to stabile regions within the same lesion. In conclusion hyperspectral imaging, automated filtering and -analysis was found to be a suitable tool to classify advanced atherosclerotic lesions.

Beck and Tews described the first practical cryptographic attack on IEEE 802.11i TKIP in November 2008, and this paper continues this line of protocol cryptanalysis. We show that their attack on TKIP can be used to create an ARP poisoning attack and a cryptographic DoS attack. Moreover, we are able to decrypt DHCP ACK packets, which are over 12 times longer than the ARP packet used by Beck and Tews. Our method of analysis recovers 596 bytes of keystream that can be used in new attacks on other control protocol messages.

Multiphoton microscopy is a techniques that fascilitates three dimensional imaging of intact, unstained tissue. Especially connective tissue has a relatively strong nonlinear optical response and can easily be imaged. Atherosclerosis is a disease where lipids accumulate in the vessel wall and there is a thickening of the intima by growth of a cap of connective tissue. The mechanical strength of this fibrous cap is of clinically importance. If the cap ruptures a thrombosis forms which can block a coronary vessel and therby causing myocardial infarction. Multiphoton microscopy can be used to image the fibrous cap and thereby determine the thickness of the cap and the structure of the connective fibres. This could possibly be developed into a diagnostic and clincal tool to monitor the vulnerability of a plaque and also to better understand the development of a plaque and effects of treatment. We have collected multiphoton microscopy images from atherosclerotic plaque in human aorta, both two photon excited fluorescens and second harmonic generated signal. The feasability of using this technique to determine the state of the plaque is explored.

Studies of immediate skin reactions are important to understand the underlying biological mechanisms involved in traumatic or chemical damage to the skin. In this study the spatial and spectral information provided by hyperspectral images was used to identify and characterize non-penetrating skin injuries in a porcine model. A hyperspectral imaging system (Hyspex, Norsk Elektro Optikk AS) was used to monitor the temporal development of minor skin injuries in an anesthetized Norwegian domestic pig. Hyperspectral data were collected in the wavelength range 400-1000 nm (VNIR), with a spectral sampling interval of 3.7 nm. The measurements were initiated immediately after inflicting the injury, and were repeated at least five times at each site with irregular frequency. The last measurement was performed 4 hours after injury. Punch biopsies (5 mm), were collected from adjacent normal skin, and at the center and the margin of each injury. The study was approved by the national animal research authority. The hyperspectral data were analyzed with respect to oxy- and deoxyhemoglobin, and erythema index. The skin biopsies were examined to determine the extent of skin damage in the bruised zones. Preliminary results show that hyperspectral imaging allows discrimination between traumatized skin and normal skin in an early phase. The extent and location of the hemorrhages can be determined from hyperspectral images. These findings might contribute to a better understanding of immediate skin reactions to minor trauma, and thereby the development of a better diagnostic modality for non-penetrating skin injuries in forensic medicine.

When performing intravascular spectroscopy there is always the possibility that there will be a thin layer of blood between the probe and the vessel wall. This will affect measurements espescially below 600 nm where blood absorption is strong (important for fluorescence and Raman measurements) and above 1400 nm where the water absorption is strong. Between these two regions (the theraputic window) the absorption is fairly low and can be neglected. This article explores the possibility of performing measurements outside the optical window by minimizing blood layer and increasing the excitation signal.

To evaluate the histopathological outcome in patients with prostate cancer operated on with radical retropubic prostatectomy.A total of 167 patients with clinically organ-localized prostate cancer treated with open radical retropubic prostatectomy between 1996 and 2001 were divided into three equally sized consecutive cohorts (cohorts I-III). The prostatectomy specimens were re-examined by two pathologists with respect to pathological tumour stage, tumour grade and surgical tumour margins.The mean preoperative prostate-specific antigen (PSA) value was statistically significantly higher in cohort I compared to cohorts II and III: 13.2, 9.0 and 8.5 ng/ml, respectively (p0.05). The incidence of locally advanced (pT3a-3b) tumours was 44% in cohort I and 20% in both cohorts II and III (p0.05). The incidence of positive tumour margins was 58% in cohort I, compared to 30% in cohort II and 13% in cohort III (p0.05). The incidence of positive intracapsular tumour margins was 55% in cohort I, compared to 25% in cohort II and 8.9% in cohort III (p0.05). The incidence of positive tumour margins in the pT2 tumours in cohorts I-III was 57%, 26% and 8.9%, respectively (p0.05). Cohort III had significantly more low-grade tumours (Gleason score 4-6; 58.9%) compared to cohorts I (31.5%) and II (34%). There was a higher incidence of Gleason scoreor=7 in the pT3 tumours compared to the pT2 tumours (80% vs 46%) and in margin-positive compared to -negative tumours (69.6% vs 48.6%) (p0.05).The decline in pT3 tumours and positive tumour margins between cohorts I-III is probably due to a gradually more strict selection of patients for radical retropubic prostatectomy. The successive reduction in positive intracapsular tumour margins is most likely due to an improved surgical technique.

Many methods for detecting and measuring vulnerable atherosclerotic plaques have been proposed. These include reflection spectroscopy, thermography, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). This paper presents an analysis and a comparison of two of these methods, near-infrared reflection spectroscopy (NIRS) and thermography. Most of the published literature evaluate methods statistically. A more analytic approach will make it easier to compare the different methods and determine if the measured signal will be strong enough in a real measurement situation. This is the approach taken in this article. Eight samples of human aorta were examined by NIRS and subsequently prepared for histology. A total of 28 measurement points were selected. A measure of the lipid content based on reflection spectra is proposed. Comparisons of this lipid measure with histology show that the lipid content in the plaques yields relatively small changes in the value of this lipid-index. Reflectance spectra from models based on the diffusion approximation for total reflectance were simulated. Temperature measurements were performed on three Watanabe heritable hyperlipidemic (WHHL) rabbits and one New Zealand white (NZW) rabbit with a thermistor-type intravascular temperature sensor. The measurements gave no significant signals which correlated with the subsequent histology. A simple analytic model was developed which indicates that a temperature increase of more than 0.01-0.04 °C at the surface of a vessel wall, due to inflammation in a plaque, is unlikely. Such a small temperature difference will probably be obscured by normal variation in the vessel wall temperature.

Purpose: The aim of this study was to quantify ocular refractive changes after a standard hyperbaric oxygen (HBO) treatment protocol and to characterize the time period of recovery. Patients and Methods: Hyperbaric oxygen therapy was given for 90 min daily at a pressure of 240 kPa for 21 days. Oxygen was administered to 20 patients using an oronasal mask and to 12 patients using a hood. Follow-up examinations were carried out 2–4 days after treatment, and thereafter regularly for up to 10 weeks in both groups. Refraction was assessed automatically and by the monocular subjective refraction method. A subgroup of nine of the 20 patients to whom oxygen was administered by an oronasal mask underwent a separate eye examination, which included crystalline lens opacity measurements and LOCS III gradings. Results: In the patients given oxygen by mask, there was a significant myopic shift in the mean spherical equivalent, which was largest 2–4 days after treatment. The shift was � 0.55 � 0.40 D in the right eye and � 0.53 � 0.42 D in the left eye. In the patients given oxygen by hood, the largest shift was observed after 12–16 days, and was � 1.06 � 0.52 D in the right eye and � 1.10 � 0.57 D in the left eye. The refractive changes returned to baseline 6 weeks and 10 weeks after HBO treatment, respectively. No significant changes in crystalline lens transparency were revealed. Conclusions: The myopic shift after HBO therapy recovers within 10 weeks and may be more pronounced when patients are given oxygen using a hood compared with using an oronasal mask.

Determining the age of injuries is an important aspect of forensic medicine. Currently, visual inspection and colorimetric measurements are the most common techniques used to assess the age of bruises on a victim's body. Bruises are caused by trauma to the skin and vasculature, and the color will depend on the age, depth, and anatomic site of the hemorrhage. Breakdown products of hemoglobin e.g. biliverdin and bilirubin possess various colors, which can be determined spectrometrically. This study presents reflection spectra collected from bruises in otherwise healthy subjects. A total of 73 spectra of 25 bruises were measured on 13 individuals in the 400-850 nm wavelength region. All injuries were caused by sports activities such as judo and soccer. The bruises were classified according to visual appearance, bilirubin content, oxygenation, and age of the injury. Only bruises with known age and cause were included in the study. Spectral changes of each hematoma were recorded over several days. Preliminary results show large variation in the spectra, caused by differences in age and depth of the bruises. This data may provide a basis for developing an algorithm to determine the age of injuries in e.g. child abuse cases.

Purpose: To examine ocular biometric variables in subjects with Down syndrome. Methods: In a population-based study we have compared ocular biometric variables in a group of 47 individuals with Down syndrome (20.0”3.9 years) with 51 control subjects (21.0”4.6 years). Results: A thinner cornea (0.48”0.04 mm vs. 0.55”0.03 mm, p∞0.001) and higher keratometry values (46.39”1.95 D vs. 43.41”1.40 D, p∞0.001) were found in the Down syndrome group than in the control group. Oblique astigmatism was commonly found in the Down syndrome individuals, showing a strong right-left specificity (right eyes’ axes in the 135ae-meridian, left eyes’ axes in the 45ae-meridian). The lens was thinner (3.27”0.29 mm vs. 3.49”0.20 mm) and the calculated lens power was weaker (17.70”2.36 D vs. 19.48”1.24 D) in the Down syndrome group than in the control group (p∞0.001 in both cases). Conclusions: Thinning of the corneal stroma may account for the steeper cornea and the high frequency of astigmatism in Down syndrome due to lower corneal rigidity. It may also be of etiological importance to the increased incidence of keratoconus in Down syndrome.

Purpose: To compare the results of penetrating and non-penetrating corneal grafting procedures in mentally retarded keratoconus patients. Methods: In the years 1974–2000 41 mentally retarded patients with keratoconus (33 with Down syndrome) were operated with corneal grafting. Mean age at operation was 36.7±10.8 years. Three different surgical procedures were used (no randomization): penetrating keratoplasty (n=16), lamellar keratoplasty (n=5) and epikeratophakia (n=20). In a retrospective study, the non-penetrating procedures (lamellar keratoplasty and epikeratophakia) were compared to the penetrating keratoplasties with regard to graft survival and frequency of serious complications. Mean follow-up time of all grafting procedures was 80±58 months. Results: All cases of serious complications (irreversible rejection, wound leakage or perforation) occurred in the penetrating keratoplasty group (p=0.0005). Older age at operation (p=0.011) adversely influenced the frequency of serious complications. Overall five-year survival was 74.9%. Graft survival was not related to surgical procedure, but rather to age at operation (poorer survival in older age, p=0.012) and degree of retardation (poorer survival in patients with more severe retardation, p=0.051). Conclusions: Because of the safety and low frequency of complications, epikeratophakia is recommended as the grafting procedure of choice in the majority of mentally retarded with keratoconus. In selected cases (good cooperation, age ≤40 years, and a good peripheral corneal thickness) penetrating keratoplasty may be performed, which, if uncomplicated, often will give better functional/optical results.