Mortality and cancer incidence among marine engineers and machinists in Iceland

A retrospective cohort study of mortality and cancer morbidity was carried out among 295 marine engineers and 182 machinists with special regard to cancer of the lung. The cohort was defined as all graduates from engineering and machinists school in Iceland during 1936-1955. During vocational training, as well as in their professional lives, marine engineers and machinists are exposed to asbestos, different kinds of mineral oils, and exhaust gases with marked individual variation as regards mode and magnitude of exposure. For deaths occurring between 1951 and 1982 information was obtained from the Statistical Bureau of Iceland. Significantly increased standardized mortality ratios were determined for cancer of the trachea, bronchus, and lung for the entire cohort. Record linkage with the Cancer Register revealed 36 cancers in the period 1955-1982. No statistically significant excess was found for the overall cancer incidence or for the incidence of cancer at any particular site. A special survey of smoking status showed that cigarette smoking was not as common among the subjects of the cohort as among the general male population in Reykjavik. These results support the suggestion that the increased mortality of lung cancer in the study group had a causal relationship to occupational exposure, particularly to asbestos exposure.     

Biomodulation of transcriptional factor NF-kappa B by ionizing radiation]

NF-kappaB (Nuclear Factor-kappaB) was described for the first time in 1986 as a nuclear protein binding to the kappa immunoglobulin-light chain enhancer. Since then, NF-kappaB has emerged as an ubiquitous factor involved in the regulation of numerous important processes as diverse as immune and inflammatory responses, apoptosis and cell proliferation. These last two properties explain the implication of NF-kappaB in the tumorigenic process as well as the promise of a targeted therapeutic intervention. This review focuses on the current knowledge on NF-kappaB regulation and discusses the therapeutic potential of targeting NF-kappaB in cancer in particular during radiotherapy.     

Impaired early insulin response to intravenous glucose in alcoholic liver cirrhosis

This study aimed at determining the release and action of insulin in liver cirrhosis. Eight non-diabetic patients with alcoholic liver cirrhosis and eight age-, sex-, and weight-matched controls were investigated. The clearance and hypoglycemic action of insulin were determined after a brief intravenous infusion of insulin (10 mU/kg). Glucose tolerance and insulin response were determined after rapid intravenous infusion of 25 g glucose. In the cirrhotic patients the decrease in glucose tolerance was associated with a) an unchanged insulin clearance, b) a decreased hypoglycemic action of insulin, and c) a marked impairment in the early insulin response and a slight, but not significant, increase in the late insulin response. In the cirrhotic group glucose tolerance varied with the early (and late) insulin response and with the hypoglycemic action of insulin. It is concluded that both insulin action and the early insulin response are impaired in alcoholic liver cirrhosis and that deterioration of the early insulin release plays an important role for deterioration of glucose tolerance.     

Radiotherapy for head and neck cancer in nonagenarian patients: a possible cornerstone?

European Archives of Oto-Rhino-Laryngology - In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or...     

Functional disability and death wishes in older Europeans: results from the EURODEP concerted action

Purpose

Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life.

Methods

Data from 11 population studies on depression in persons aged 65 and above were pooled, yielding a total of 15,890 respondents. Level of functional disability was trichotomised (no, intermediate, high). A person was considered to have death wishes if the death wish/suicidal ideation item of the EURO-D scale was endorsed. Odds ratios for death wishes associated with functional disability were calculated in a multilevel logistic regression model.

Results

In total, 5 % of the men and 7 % of the women reported death wishes. Both intermediate (OR 1.89, 95 % CI 1.42; 2.52) and high functional disability (OR 3.22, 95 % CI 2.34; 4.42) were associated with death wishes. No sex differences could be shown. Results remained after adding depressive symptoms to the model.

Conclusions

Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.     

Radiotherapy among nonagenarians with anal or rectal carcinoma:should we avoid or adapt treatment?

Dear editor, Radiotherapy is a cornerstone in the management of anal or rectal cancer. Because elderly patients are often excluded from clinical trials, little is known about radi-otherapy's therapeutic index (efficacy/toxicity ratio) in the geriatric population [1]. Still, the ageing of popula-tion imposes the challenge to treat older cancer patients and probably to adjust their treatment [2]. A few studies reported data on radiation-induced toxicities in nonage-narian patients, but data on efficacy are still scarce.     

Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy.

BACKGROUND: The oncology community usually perceives phase I oncology trials as associated with poor or limited benefits and substantial risks. There is scarce data concerning outcome and survival of patients enrolled in current phase I oncology trials. PATIENTS AND METHODS: We reviewed all phase I oncology trials conducted by investigators from the Adult Phase I Unit at Institut Gustave Roussy from 2003 to 2006. We report data concerning patient demographics, treatment outcome, toxicity, survival and type of care after trial exit. RESULTS: We analyzed 10 trials involving 180 participants. The overall response rate was 7.2%. Disease control (objective response plus stable disease) was achieved in 48.2% of patients. The rate of toxic death was 0.5%. In all, 38% of patients had at least one episode of grade 3 or 4 toxic events. The median progression-free survival and the median overall survival (OS) were 2.3 and 8.7 months, respectively. On multivariate analysis, a time between diagnosis of disease and inclusion in the phase I trial > or =24 months and evidence of disease control were statistically significant predictors of improved OS. CONCLUSION: Current phase I oncology trials are safe and are associated with clinical benefit in a substantial proportion of patients.     

Self-association and cyclodextrin solubilization of drugs

Phase-solubility diagrams are frequently used to calculate stoichiometry of drug/cyclodextrin complexes. Linear diagrams (A(L)-type systems) are thought to indicate that the complexes are first order with respect to cyclodextrin and first or higher order with respect to the drug. Positive deviation from linearity (A(P)-type systems) are thought to indicate formation of complexes that are first order with respect to the drug but second or higher order with respect to cyclodextrin. The phase solubility of several different compounds, i.e., cholesterol, ibuprofen, diflunisal, alprazolam, 17beta-estradiol and diethylstilbestrol, and various charged and uncharged cyclodextrins was investigated. Phase-solubility diagrams of cholesterol in aqueous cyclodextrin solutions were all of A(P) type. However, the phase-solubility diagrams obtained with charged cyclodextrins could not be fitted to complexes of second or higher order with respect to cyclodextrin. The phase-solubility diagrams of ibuprofen and diflunisal were of A(L) type with slope greater than unity indicating formation of 2:1 drug/cyclodextrin complexes. However, Job's plots and space filling docking studies indicated that 1:1 complexes were formed. These and other observations show that stoichiometry of drug/cyclodextrin complexes cannot be derived from simple phase-solubility studies. Furthermore, the results indicate that drug/cyclodextrin complexes can self-associate to form water-soluble aggregates, which then can further solubilize the drug through non-inclusion complexation.