Peer Kåre Lilleng

Postal survey on airborne occupational exposure and respiratory disorders in Norway: causes and consequences of non-response.

STUDY OBJECTIVE--The aim was to examine causes for non-response in a community survey, and how non-response influences prevalence estimates of some exposure and disease variables, and associations between the variables. DESIGN--This was a cross sectional questionnaire study with two reminder letters. The questionnaire asked for information on smoking habits, occupational airborne exposure and respiratory disorders. SETTING--A random sample of 4992 subjects from the general population aged 15-70 years of Hordaland County, Norway. MAIN RESULTS--The overall response rate was 90%, with a 63% response to the initial letter. The response rates to the first and second reminder letters were 56% and 36% respectively. In 20% of the non-respondents an uncompleted questionnaire was returned with cause for non-response; in two thirds of these the cause for non-response was that the subject was not resident at the mailing address. A home visit to a random sample of 50 urban non-respondents provided further information on 29 subjects. A wrong address at the Central Population Registry and the subjects feeling of lack of personal benefit from a postal survey were the major reasons for non-response. Smokers were late respondents and subjects with respiratory disorders tended to be early respondents. CONCLUSION--The main reasons for non-response were a wrong mailing address and a feeling of lack of personal benefit from responding. Using only the initial letter would have changed the estimated prevalence of smokers from 39% to 35%. Otherwise, the estimated prevalence of the exposure and disease variables as well as the associations between them were only slightly changed after including the respondents to the first and second reminder letters.

Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study

BackgroundThe main forms of mercury (Hg) exposure in the general population are methylmercury (MeHg) from seafood, inorganic mercury (I-Hg) from food, and mercury vapor (Hg0) from dental amalgam restorations. While the distribution of MeHg in the body is described by a one compartment model, the distribution of I-Hg after exposure to elemental mercury is more complex, and there is no biomarker for I-Hg in the brain. The aim of this study was to elucidate the relationships between on the one hand MeHg and I-Hg in human brain and other tissues, including blood, and on the other Hg exposure via dental amalgam in a fish-eating population. In addition, the use of blood and toenails as biological indicator media for inorganic and organic mercury (MeHg) in the tissues was evaluated.MethodsSamples of blood, brain (occipital lobe cortex), pituitary, thyroid, abdominal muscle and toenails were collected at autopsy of 30 deceased individuals, age from 47 to 91 years of age. Concentrations of total-Hg and I-Hg in blood and brain cortex were determined by cold vapor atomic fluorescence spectrometry and total-Hg in other tissues by sector field inductively coupled plasma-mass spectrometry (ICP-SFMS).ResultsThe median concentrations of MeHg (total-Hg minus I-Hg) and I-Hg in blood were 2.2 and 1.0 μg/L, and in occipital lobe cortex 4 and 5 μg/kg, respectively. There was a significant correlation between MeHg in blood and occipital cortex. Also, total-Hg in toenails correlated with MeHg in both blood and occipital lobe. I-Hg in both blood and occipital cortex, as well as total-Hg in pituitary and thyroid were strongly associated with the number of dental amalgam surfaces at the time of death.ConclusionIn a fish-eating population, intake of MeHg via the diet has a marked impact on the MeHg concentration in the brain, while exposure to dental amalgam restorations increases the I-Hg concentrations in the brain. Discrimination between mercury species is necessary to evaluate the impact on Hg in the brain of various sources of exposure, in particular, dental amalgam exposure.

Severe nigrostriatal degeneration without clinical parkinsonism in patients with polymerase gamma mutations

The role of mitochondria in the pathogenesis of neurodegeneration is an area of intense study. It is known that defects in proteins involved in mitochondrial quality control can cause Parkinsons disease, and there is increasing evidence linking mitochondrial dysfunction, and particularly mitochondrial DNA abnormalities, to neuronal loss in the substantia nigra. Mutations in the catalytic subunit of polymerase gamma are among the most common causes of mitochondrial disease and owing to its role in mitochondrial DNA homeostasis, polymerase gamma defects are often considered a paradigm for mitochondrial diseases generally. Yet, despite this, parkinsonism is uncommon with polymerase gamma defects. In this study, we investigated structural and functional changes in the substantia nigra of 11 patients with polymerase gamma encephalopathy. We characterized the mitochondrial DNA abnormalities and examined the respiratory chain in neurons of the substantia nigra. We also investigated nigrostriatal integrity and function using a combination of post-mortem and in vivo functional studies with dopamine transporter imaging and positron emission tomography. At the cellular level, dopaminergic nigral neurons of patients with polymerase gamma encephalopathy contained a significantly lower copy number of mitochondrial DNA (depletion) and higher levels of deletions than normal control subjects. A selective and progressive complex I deficiency was seen and this was associated with a severe and progressive loss of the dopaminergic neurons of the pars compacta. Dopamine transporter imaging and positron emission tomography showed that the degree of nigral neuronal loss and nigrostriatal depletion were severe and appeared greater even than that seen in idiopathic Parkinsons disease. Despite this, however, none of our patients showed any signs of parkinsonism. The additional presence of both thalamic and cerebellar dysfunction in our patients suggested that these may play a role in counteracting the effects of basal ganglia dysfunction and prevent the development of clinical parkinsonism.

Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease

Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.

Molecular Pathogenesis of Polymerase Gamma–Related Neurodegeneration

Polymerase gamma (POLG) mutations are a common cause of mitochondrial disease and have also been linked to neurodegeneration and aging. We studied the molecular mechanisms underlying POLG‐related neurodegeneration using postmortem tissue from a large number of patients.

Wear particles and ions from cemented and uncemented titanium-based hip prostheses—A histological and chemical analysis of retrieval material

Wear debris-induced inflammation is considered to be the main cause for periprosthetic osteolysis in total hip replacements (THR). The objective of this retrieval study was to examine the tissue reactions and exposure to metal ions and wear particles in periprosthetic tissues and blood samples from patients with titanium (Ti)-based hip prostheses that were revised due to wear, osteolysis, and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30 THR-patients revealed numerous wear debris-loaded macrophages, inflammatory cells, and necrosis in both groups. Particle load was highest in tissues adjacent to loosened cemented Ti stems that contained mainly submicron zirconium (Zr) dioxide particles. Particles containing pure Ti and Ti alloy elements were most abundant in tissues near retrieved uncemented cups. Polyethylene particles were also detected, but accounted only for a small portion of the total particle number. The blood concentrations of Ti and Zr were highly elevated in cases with high abrasive wear and osteolysis. Our findings indicate that wear particles of different chemical composition induced similar inflammatory responses, which suggests that particle size and load might be more important than the wear particle composition in periprosthetic inflammation and osteolysis.

'Missed' micrometastases--the extent of the problem.

The value of detecting micrometastases in patients with breast cancer has been debated for many years. The aim of this study was to determine whether and why such tumour deposits are missed at the time of reporting. The series comprised 272 patients treated surgically for breast carcinoma. For node-negative cases, the haematoxylin and eosin stained slides were re-examined. Those still remaining negative were stained with epithelial membrane antigen marker (EMA). Hilar sections were used in 76% of cases. Micrometastases were found in 35 cases reported as node-negative: 15 being identified on re-examination and 20 after staining with EMA, a gain of 44%, including 20 of embolic type. All were found in hilar sections of the nodes. The patients in whom micrometastases were found on further examination had significantly smaller tumour deposits than those reported as node-positive. In cases with infiltrating ductal carcinoma these presented as embolic growth, while those with infiltrating lobular carcinoma, for example, tended to colonize the nodal parenchyma, giving nodal growth. Differentiation between these growth patterns enables pathologists to distinguish between the dangerous embolic type and the less important nodal growth. In conclusion, many of these micrometastases can be detected if the slides reported as node-negative on first reading are re-examined. In those remaining negative, immunohistochemical staining is recommended.

Fatal injury as a function of rurality-a tale of two Norwegian counties

BackgroundMany studies indicate rural location as a separate risk for dying from injuries. For decades, Finnmark, the northernmost and most rural county in Norway, has topped the injury mortality statistics in Norway. The present study is an exploration of the impact of rurality, using a point-by-point comparison to another Norwegian county.MethodsWe identified all fatalities following injury occurring in Finnmark between 2000 and 2004, and in Hordaland, a mixed rural/urban county in western Norway between 2003 and 2004 using data from the Norwegian Cause of Death Registry. Intoxications and low-energy trauma in patients aged over 64 years were excluded. To assess the effect of a rural locale, Hordaland was divided into a rural and an urban group for comparison. In addition, data from Statistics Norway were analysed.ResultsFinnmark reported 207 deaths and Hordaland 217 deaths. Finnmark had an injury death rate of 33.1 per 100,000 inhabitants. Urban Hordaland had 18.8 deaths per 100,000 and rural Hordaland 23.7 deaths per 100,000. In Finnmark, more victims were male and were younger than in the other areas. Finnmark and rural Hordaland both had more fatal traffic accidents than urban Hordaland, but fewer non-fatal traffic accidents.ConclusionsThis study illustrates the disadvantages of the most rural trauma victims and suggests an urban-rural continuum. Rural victims seem to be younger, die mainly at the site of injury, and from road traffic accident injuries. In addition to injury prevention, the extent and possible impact of lay people’s first aid response should be explored.

Secretoglobins in the human pituitary: high expression of lipophilin B and its down-regulation in pituitary adenomas

Secretoglobins are small secreted proteins, the expression of which has mostly been associated with secretory mucosal epithelia. Several secretoglobins have been implicated in the development of various human cancers. Allelic deletions of chromosome 11q13 correlates with the invasiveness of pituitary tumors. Intriguingly, several secretoglobin genes are located on 11q13; however, for most of these genes the expression in the pituitary and pituitary tumors have not been investigated. Antibodies specific for the secretoglobin lipophilin B (SCGB1D2, BU101) were developed and used in an immunohistochemical analysis of a human normal tissue microarray. Prominent lipophilin B immunoreactivity was found in the secretory cells of the anterior pituitary. Eight of nine analyzed pituitary adenomas showed a reduction in lipophilin B immunoreactivity compared to normal pituitary. However, there was no apparent association between lipophilin B immunoreactivity and hormone production or tumor invasiveness. Expression of eight different secretoglobin mRNAs were analyzed in normal pituitary and the pituitary adenoma cell line HP75 by highly specific quantitative real-time reverse transcription-PCR assays. Lipophilins B and C (SCGB2A1, mammaglobin B) were the most prominently expressed secretoglobin mRNAs in the pituitary. No secretoglobin mRNA was detected in the HP75 cells. The present report demonstrates, for the first time, lipophilin B expression in the pituitary and its apparent down-regulation in pituitary adenomas.

Homicides in Western Norway, 1985-2009, time trends, age and gender differences

This retrospective study from Western Norway is based on the cases of 196 homicide victims from 1985 to 2009. The median age of the victims was 35 years, in both genders. Within the cases, 113 of the victims were male and 83 female, 28 victims were under the age of 18, and 19 victims were not native Norwegians. Ethanol was detected in the blood of a higher proportion of male compared to female victims, whereas a higher proportion of female compared to male victims had both illegal/legal drugs detected in their blood. Most perpetrators were male. Men were most often killed by an acquaintance, women by their present or former intimate partner. In 14 cases of intimate partner homicide the perpetrator committed suicide after killing their female partner. The dominant scene of crime was private homes. Most victims were killed by blunt force, sharp force or gunshot. The head was the body region most often injured in the homicide victims. Female victims were more often killed by manual strangulation than male victims.