Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study

Purpose Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumor-cell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence. Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux disease (GERD) were evaluated Methods Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the study. HPV DNA was determined with MY09/11 and GP5+/6+ nested PCR and SPF10 PCR hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire concerning risk factors was filled in. Results Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis. Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated with survival, although it correlated with heavy drinking. Conclusion In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and promoted early carcinogenesis. This work was supported by grants from Cancer Societies of Finland, Helsinki University Hospital Research Funds, Finnish Dental Society Apollonia, Stockholm Cancer Society and Laryngfonden, Sweden.     

Mobility limitations in persons with psychotic disorder: findings from a population-based survey

BACKGROUND: There are few reports on mobility limitations in persons with psychotic disorder although restrictions in mobility may aggravate the general functional limitations of these patients. Our aim was to investigate mobility limitations among subjects with psychotic disorder in a general population-based sample. METHODS: A nationally representative sample of 6,927 persons aged 30 and older self-reported mobility limitations in an interview and was examined in performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia, other nonaffective psychotic disorders and affective psychoses. RESULTS: Self-reported mobility limitations were highly prevalent in persons with schizophrenia and other nonaffective psychosis, but not in the affective psychosis group. After adjusting for age and sex, persons with schizophrenia and other nonaffective psychoses but not affective psychoses had significantly increased odds of having both self-reported and test-based mobility limitations as well as weak muscle strength. Schizophrenia remained an independent predictor of mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Among persons with nonaffective psychoses, higher levels of negative symptoms predicted mobility limitations. CONCLUSION: Self-reported mobility limitations are prevalent already at a young age in persons with schizophrenia and other nonaffective psychotic disorders, and among older persons with these disorders both self-reported limitations and measured performance tests show lower capacity in mobility. Difficulties in mobility are associated with negative symptoms. Mental health care professionals should pay attention to mobility limitations in persons with psychotic disorder.     

Anticoagulants and antiplatelet agents and the risk of development and recurrence of chronic subdural haematomas

Seventy-one patients from northern Sweden were diagnosed with chronic subdural haematomas (CSDH) and treated at the Department of Neurosurgery at Umeå University Hospital over 12 months. Fifty-four patients with CSDH had a history of head trauma (trauma group), while 17 patients had no previous head trauma (non-trauma group). In the non-trauma group 71% of patients were treated with anticoagulants or antiplatelet aggregation agents (AAA) compared to 18% in the trauma group. Considering only AAA, 59% of the non-trauma patients were treated with these drugs versus 17% of patients in the trauma group. The recurrence rate for all patients was 17%. These findings confirm that the use of anticoagulants and AAA is over-represented in patients with non-traumatic CSDH. In our study, recurrence was not associated with previous use of anticoagulants or AAA.     

How to use bibliometric methods in evaluation of scientific research? An example from Finnish schizophrenia research

We present bibliometric methods that can be utilized in evaluation processes of scientific work. In this paper, we present some practical clues using Finnish schizophrenia research as an example and comparing the research output of different institutions. Bibliometric data and indicators including publication counts, impact factors and received citations were used as tools for evaluating research performance in Finnish schizophrenia research. The articles and citations were searched from the Web of Science database. We used schizophrenia as a keyword and defined address Finland, and limited years to 1996-2005. When we analysed Finnish schizophrenia research, altogether 265 articles met our criteria. There were differences in impact factors and received citations between institutions. The number of annually published Finnish schizophrenia articles has tripled since the mid-1990s. International co-operation was common (43%). Bibliometric methods revealed differences between institutions, indicating that the methods can be applied in research evaluation. The coverage of databases as well as the precision of their search engines can be seen as limitations. Bibliometric methods offer a practical and impartial way to estimate publication profiles of researchers and research groups. According to our experience, these methods can be used as an evaluation instrument in research together with other methods, such as expert opinions and panels.     

Geographic variation and sociodemographic characteristics of psychotic disorders in Finland

BACKGROUND: Geographical variation and sociodemographic characteristics may differ in affective and nonaffective psychotic disorders. We examined the geographical variation in the lifetime prevalence of psychotic disorders in a comprehensive general population study. METHOD: A nationally representative sample of 8028 Finns aged 30 or over was screened for psychotic and bipolar I disorders and interviewed with the Structured Clinical Interview for DSM-IV. Best-estimate DSM-IV diagnoses were formed by combining interview and case note data. Nationwide health care register data were used for the nonrespondents. Associations with sociodemographic features, place of birth and residence in urban or rural areas and in five regions, and migration between the regions were examined. RESULTS: Schizophrenia and other nonaffective psychoses, but not affective psychoses, showed prominent regional variation, with highest odds found for schizophrenia among those born in the North (OR 7.72 95%CI 2.48-24.04) and the East (OR 3.99 95%CI 1.22-13.11). The risk of any psychotic disorder was lower for those born in urban areas (OR 0.73 95%CI 0.54-0.98), but no associations were found for separate diagnostic groups. Region of birth was the strongest determinant of geographical variation when both place of birth and residence were accounted for. Selective migration was not found. Education and income were higher and being employed more common in subjects with affective psychosis than in subjects with other psychotic disorders. CONCLUSIONS: Large area variation is more important than urban-rural disparity in psychotic disorders in Finland. Affective psychoses were different from nonaffective psychoses in terms of both regional variation and sociodemographic features.     

Development of a rapid assay methodology for antimicrobial susceptibility testing of Staphylococcus aureus

Development of a new phenotypic technique for rapid antimicrobial susceptibility testing (AST) of methicillin-resistant Staphylococcus aureus is presented. The new technique combines bacterial culturing and specific immunometric detection in a single separation-free process. The technique uses dry chemistry reagents and the recently developed two-photon excitation detection technology, which allows online detection of bacterium-specific growth. The performance of the new technique was evaluated by monitoring the growth of S. aureus reference strains and determining their susceptibility to oxacillin. In the direct analysis of clinical specimens, method specificity and tolerance to interferences caused by other bacteria present in the sample are pivotal. Other bacteria can compete with the bacteria of interest for nutrients, for example. Specificity and tolerance were studied against Staphylococcus epidermidis reference strains. The results suggest that the new technique could allow rapid AST directly from clinical samples within 6 to 8 h. Such a rapid and simple testing methodology would be a valuable tool in clinical microbiology because it would shorten the turnaround times of microbiologic analyses. Advantages of the new approach in relation to conventional methods are discussed.     

Do changes in cardiovascular risk factors explain the increasing socioeconomic difference in mortality from ischaemic heart disease in Finland?

STUDY OBJECTIVE: To estimate the extent to which changes in blood pressure, smoking, and serum cholesterol concentration explain the observed increase in socioeconomic differences in mortality from ischaemic heart disease (IHD) in Finland during the past 20 years. DESIGN: Predicted changes in mortality from IHD were calculated using logistic regression models with the risk factor levels assessed by cross sectional population surveys conducted in 1972, 1977, 1982, and 1987. The subjects included white collar and blue collar workers and farmers. The predicted changes were compared with the observed mortality changes in the same socioeconomic groups in the total population of the same geographical area. SETTING: North Karelia and Kuopio provinces, eastern Finland. PARTICIPANTS: 16,741 men and 16,389 women aged 30-59 randomly drawn from the population registers of the study areas. Mortality data were obtained from the total population in the same areas. MAIN RESULTS: In men, the changes in diastolic blood pressure, total serum cholesterol, and smoking predicted a 28% decline in the mortality from IHD among white collar workers, a 30% decline among blue collar workers, and a 33% decline in farmers. Observed declines in the same socioeconomic groups were 61%, 40%, and 37%, respectively. In women, the predicted decline was 41% among white collar workers, 35% among blue collar workers, and 39% among farmers. The respective observed declines were 57%, 43%, and 20%. CONCLUSIONS: Less than half of the decline in IHD mortality among white collar men was explained by the risk factor changes, while they explained 75% of the decline among blue collar men and 89% of the decline among male farmers. Changes in risk factors did not explain the increasing difference in IHD mortality between the socioeconomic groups, especially among men.

 

     

A peptide inhibitor of vascular adhesion protein-1 (VAP-1) blocks leukocyte-endothelium interactions under shear stress

Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule mediating leukocyte interactions with blood vessels during leukocyte extravasation. Molecularly VAP-1 is a cell-surface-expressed ecto-enzyme belonging to the group of semicarbazide-sensitive amine oxidases (SSAO; EC 2.4.6.3), which deaminate primary amines. Here we asked whether peptides displaying a suitable free amine group could be a substrate or inhibitor of SSAO and thus regulate VAP-1-mediated leukocyte adhesion. On the basis of a molecular model of VAP-1, we designed synthetic peptides that fit to the substrate channel of VAP-1. One of these lysine-containing peptides effectively inhibits VAP-1-dependent lymphocyte rolling and firm adhesion to primary endothelial cells under physiologically relevant shear conditions. The same peptide inhibits the SSAO activity of endothelial and recombinant VAP-1 in a selective and long-lasting manner. We also show that all enzymatically active VAP-1 is displayed on the cell surface. Our results suggest that, in addition to soluble amines, specific cell-surface-bound molecules containing free NH(2) groups in a suitable position may modulate the enzymatic activity of SSAO. Moreover, the inhibitory peptide diminishes leukocyte interactions with endothelial cells under conditions of shear, and thus it may be useful to treat inflammatory conditions.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.