The prognostic impact of cyclin dependent kinase inhibitors p21WAF1, p27Kip1, and p16INK4/MTS1 in adenocarcinomas of the uterine cervix: an immunohistochemical evaluation of expression patterns in population-based material from 142 patients with international federation of gynecology and obstetrics stage I and II adenocarcinoma

BACKGROUND: The authors assessed the prognostic significance of abnormal cyclin dependent kinase inhibitor (CDKI) expression in adenocarcinomas of the uterine cervix. METHODS: Population-based, archival material from patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I and II cervical adenocarcionmas from 2 5-year periods (1976-1980, n = 82 patients; 1986-1990, n = 142 patients) was examined for expression of p21(WAF1), p27(Kip1), and p16(INK4/MTS1) using immunohistochemical techniques. RESULTS: Rates of tumors with low levels of nuclear expression of p27 and p16 were lower during the period 1976-1980 (P < 0.01), suggesting bias due to unbuffered formalin. Analyses that were restricted to patients from 1986-1990 showed positive associations between all three CDKIs (P < 0.05). Low p16 expression was associated with higher FIGO stage (P = 0.01), age older than 55 years (P = 0.01), and deep invasion (P = 0.003). No significant associations with stage, age, or histopathologic parameters were found for p21 or p27. Significant associations with tumor differentiation were not seen for any CDKI. Kaplan-Meier plots showed diverging survival curves for p21 and p27 expression, but the differences were not significant. In multivariate analysis, low p27 expression and high p16 expression were strong predictors of a poor prognosis (p27: < 40% nuclear staining; P = 0.001; hazard ratio, 3.18; p16: < 40% nuclear staining; P < 0.001; hazard ratio, 0.16). Low p27 expression was of prognostic significance only if it was analyzed together with p16 expression. Further evaluation indicated that patients with different phenotypic p27/p16 combinations may have different outcomes. CONCLUSIONS: Aberrant expression patterns of CDKIs were predictors of prognosis for patients with FIGO Stage I or II cervical adenocarcinoma. Analysis of CDKI expression in this patient group may prove clinically useful.     

Sixteen days

When does a human being begin to exist? We argue that it is possible, through a combination of biological fact and philosophical analysis, to provide a definitive answer to this question. We lay down a set of conditions for being a human being, and we determine when, in the course of normal fetal development, these conditions are first satisfied. Issues dealt with along the way include: modes of substance-formation, twinning, the nature of the intra-uterine environment, and the nature of the relation between fetus and mother (connection, parthood, dependence).     

Sense of coherence predicts change in life satisfaction among home-living residents in the community with mental health problems: a 1-year follow-up study

Objectives There is a call for a further investigation of Sense of Coherence (SOC), the central concept in salutogenesis, and its relation to health and life satisfaction. No previous studies have investigated the utility of SOC versus mental symptoms for the prediction of life satisfaction among people with chronic mental health problems (MHP). Methods The present study has a prospective design including a baseline assessment and a 1-year follow up. We recruited 107 adults from the community health care system. SOC was measured by the Sense of Coherence questionnaire, mental symptoms by the Symptom Checklist-90 revised and life satisfaction by The Quality of Life Scale (all Norwegian versions). Results The results show that while SOC predicts change in life satisfaction (standardized beta coefficient for SOC was 0.39, P = 0.014), mental symptoms did not (standardized beta coefficient 0.00, P = 1.0). Conclusions These findings emphasize the importance of assessing factors that may explain differences in life satisfaction over and above mental symptoms among people with MHP. The results indicate that improving SOC among people with MHP might provide important opportunities for improving their life satisfaction.     

Biomarkers of endothelial activation and thrombosis in tunnel construction workers exposed to airborne contaminants

Objectives

The aims were to study biomarkers of systemic inflammation, platelet/endothelial activation and thrombosis in tunnel construction workers (TCW).

Methods

Biomarkers and blood fatty acids were measured in blood of 90 TCW and 50 referents before (baseline) and towards the end (follow-up) of a 12 days work period. They had been absent from work for 9 days at baseline. Air samples were collected by personal sampling.

Results

Personal thoracic air samples showed geometric mean (GM) particulate matter and α-quartz concentrations of 604 and 74 µg/m³, respectively. The arithmetic mean (AM) concentration of elemental carbon was 51 µg/m³. The GM (and 95% confidence interval) concentration of the pro-inflammatory cytokine TNF-α decreased from 2.2 (2.0–2.4) at baseline to 2.0 pg/mL (1.8–2.2) (p?=?0.02) at follow-up among the TCW. Also the platelet activation biomarkers P-selectin and CD40L decreased significantly [25.4 (24.1–26.6) to 24.4 (22.9–26.0)] ng/mL, p?=?0.04 and 125 (114–137) to 105 (96–115) pg/mL, p?<?0.001, respectively. ICAM-1 concentrations increased from 249 (238–260) to 254 (243–266) ng/mL (p?=?0.02). No significant alterations were observed among the referents when assessed by paired sample t test. Unbeneficial alterations in blood fatty acid composition were observed between baseline and follow-up, mainly among referents.

Conclusions

TCW had slightly reduced systemic inflammation and platelet activation although highly exposed to particulate matter, α-quarz and diesel exhaust, which might be due to increased physical activity during the exposure period. The slightly increased ICAM-1 may indicate monocyte recruitment to the lungs. The diet was substantially altered towards a less beneficial fatty acid profile.

     

Bioequivalence determination of topical ketoprofen using a dermatopharmacokinetic approach and excised skin penetration

Ketoprofen is a photolabile drug. The aim of the present study was to compare the bioavailability of ketoprofen in a photo-stabilised formulation with a gel without photoprotection using a new dermatopharmacokinetic tape-stripping model and an established ex vivo penetration method using human skin. Analyses of the stratum corneum showed that during the first 45 min about 12 microg/cm2 ketoprofen was absorbed into the skin from the formulations. The area under the ketoprofen content-time curve (AUC0-6 h) for the ratio photo-stabilised gel/transparent gel was 73% with a 90% confidence interval (CI) 65-83. The rate of penetration of ketoprofen through isolated skin was approximately 0.2 microg/cm2 h for both formulations. AUC0-36 h for the ratio was 84% with 90% CI 64-105. Thus, the two methods did not disagree in terms of relative efficacy of the two gels. However, the difference obtained in vivo was statistically significant, whereas no significant data arise from the ex vivo study. Comparing the amount of ketoprofen in the skin after 45 min with the amount penetrated through the excised skin during 36 h, suggests a change in the thermodynamic activity of ketoprofen during the exposure. A supersaturated formulation may well have been formed initially due to evaporation of ethanol.     

Psychometric properties of the Brief Pain Inventory among patients with osteoarthritis undergoing total hip replacement surgery

Background  

Pain is a cardinal symptom of osteoarthritis (OA) of the hip and important for deciding when to operate. This study assessed the internal consistency reliability, validity and responsiveness of the Brief Pain Inventory (BPI) among patients with OA undergoing total hip replacement (THR).     

A comparison of sexual behaviour and attitudes of healthy adolescents in a Danish high school in 1982, 1996, and 2001

AIM: To assess changes in sexual behaviour among students at a high school in Denmark from 1982 to 2001. METHODS: An anonymous self-administered questionnaire was used to compare data from three identical cross-sectional surveys performed in 1982, 1996, and 2001. RESULTS: Girls: More girls reported their first sexual intercourse before their 16th birthday in 2001 (42%) than in 1996 (29%) In 1982 it was also 42% (Chi-square for trend: p = 0.003). Fewer girls with no regular partner used condoms for their personal protection in 2001 (2%) than in 1996 (9%) and 1982 (0%) (Chi-square for trend p = 0.016). The proportion of girls with no regular partner who considered protection from sexually transmitted disease important for their choice of contraception was 39% in 2001 compared with 71% in 1996 and only 10% in 1982 (Chi-square for trend: p < 0.0001).Boys: More boys reported sexual debut before their 16th birthday in 2001 (40%) than in 1996 (37%) and 1982 (24%) (Chi-square for trend: p = 0.023). For boys with no regular partner, condom was preferred for personal protection by 85% in 2001, 91% in 1996 and 61% in 1982 (Chi-square for trend p = 0.007). Protection against sexually transmitted infection declined, especially among boys with no regular partner, from 51% in 2001 to 72% in 1996 and 21% in 1982 Chi-square for trend: p < 0.0001).The tendency towards earlier sexual debut and less use of safe sex practices to protect against sexually transmitted infections (STI) was accompanied by a rise in the number of detected STIs during this period. CONCLUSIONS: The period from 1982 to 1996 during which sexual attitudes were directed toward safer sex seems to have given way to a reverse trend in the period from 1996 to 2001. These findings may have significant implications for health care authorities organising preventive strategies for healthy adolescents.     

Yersinia enterocolitica Outbreak Associated with Ready-to-Eat Salad Mix, Norway, 2011

In 2011, an outbreak of illness caused by Yersinia enterocolitica O:9 in Norway was linked to ready-to-eat salad mix, an unusual vehicle for this pathogen. The outbreak illustrates the need to characterize isolates of this organism, and reinforces the need for international traceback mechanisms for fresh produce.