Impact of work environment on cardiovascular diseases in Denmark.

STUDY OBJECTIVE--The aim was to estimate the quantitative impact of working conditions on cardiovascular diseases in Denmark. DESIGN--The study was based on a review of recent epidemiological research publications in which relative risks were estimated and risk factor prevalences were determined. The impact of working conditions was quantified by means of aetiological fractions. SETTING--The aetiological fractions were estimated on the Danish population. MAIN RESULTS--16% of the premature cardiovascular mortality in men and 22% in occupationally active women is avoidable through interventions in the work environment. If "sedentary" work is included in the occupational risk factors, the aetiological fractions reach 51% for men and 55% for women. Taken separately, the major aetiological fractions for cardiovascular risk factors at work are respectively (women in parentheses) 6% (14%) for monotonous high paced work, 7% (7%) for shift work, and 2% (2%) for passive smoking. CONCLUSIONS--The aetiological fractions show that working conditions play a considerable role in cardiovascular diseases. Furthermore they might widen the focus of preventive cardiology from interventions directed only at individual and lifestyle risk factors to interventions directed also at working conditions.     

Contrast enhancement of cerebral infarcts. Incidence and clinical value in different states of cerebral infarction

Summary Information obtained from CT scan after contrast administration was evaluated in 59 consecutive stroke patients. CT scans before and after contrast administration were performed 3 days and 21/2 weeks after stroke. A plain CT scan was repeated 6 months later. Contrast enhancement was practically not seen on the first examination, but was seen in 46% on the second examination. There was a close relationship between the occurrence of contrast enhancement and the socalled fogging effect. Contrast scanning gave additional information only when this effect was present. Plain CT scans 3 days after stroke were superior to contrast scans taken at any time for detecting and visualizing cerebral infarcts.     

Mortality among bricklayers and carpenters/cabinet makers.

Mortality among members of two medium-sized trade unions, the union of carpenters/cabinet makers and the union of bricklayers, has been studied during the period 1.1.71-31.12.75, primarily to investigate if the greater exposure to dust and organic solvents of the carpenters/cabinet makers caused any increase in the mortality from lung diseases. The study did not reveal any significant differences in mortality regarding any category of diagnoses except suicide, when the analysis was based on the main diagnosis recorded on the death certificate. However, when including underlying causes of death too, statistically significant increased death rates from larynx cancer, asthma, bronchitis and emphysema were found among the bricklayers, as compared with the carpenters/cabinet makers. No explanation can be given for these observations. They may be a result of an unequal distribution of confounding variables in the two groups, or they may reflect various grades and forms of "Healthy Worker" selection. This study is a cross-section study and such studies and longitudinal studies over a period of a few years of occupational mortality are very sensitive to the selection of the occupational groupings. The analysis is based on deaths among life-insured members under the age of 67 years, in the two trade unions. Copies of the death certificates were obtained from the National Health Service and then coded by us along the lines indicated by the NHS.     

Preparation of cell-free feline oncornavirus-associated cell membrane antigen.

Cell-free feline oncornavirus-associated cell membrane antigen (FOCMA) was prepared from a feline lymphoblastoid cell line of tumor origin (FL-74). Membrane fractions, separated on sucrose density gradients, and papain-solubilized products were found to contain FOCMA as determined by their capacity to inhibit reference cytotoxic cat antisera.     

Nephrotoxicity by dicloxacillin and gentamicin in 163 patients with intertrochanteric hip fractures

Of 163 patients with intertrochanteric hip fractures 87 received 2 g dicloxacillin and 240 mg of gentamicin preoperatively, and 76 patients had no antibiotic prophylaxis. Preoperative antibiotic prophylaxis was not shown to have any significant effect on wound infections. However, 16 reversible and 1 irreversible cases of kidney toxicity were found among patients receiving antibiotic prophylaxis, whereas there were only four cases of reversible kidney damage among the patients not receiving antibiotics.     

Effects of the Environmental Oestrogens Bisphenol A,Tetrachlorobisphenol A,Tetrabromobisphenol A, 4‐Hydroxybiphenyl and 4,4′‐Dihydroxybiphenyl on Oestrogen Receptor Binding,Cell Proliferation and Regulation of Oestrogen Sensitive Proteins in the Human Breast Cancer Cell Line MCF‐7

Abstract: Bisphenol A is extensively used in the manufacturing of epoxy resins and polycarbonate plastics, whereas several brominated and chlorinated analogues are used as flame retardants and intermediates in the plastic industry. Due to the structural relationship between these chemicals and the high production volumes, we wanted to characterize and compare their potential oestrogen‐like potency using several end‐points in MCF‐7 cells: induction of pS2 protein and progesterone receptor, reduction of oestrogen receptor level, and stimulation of cell growth. Bisphenol A, tetrachloro‐ and tetrabromo‐bisphenol A, 4‐hydroxybiphenyl and 4,4′‐dihydroxybiphenyl all showed oestrogen‐like properties in MCF‐7 cells. The chemicals tested had affinity to the oestrogen receptor isolated from MCF‐7 cells, although their EC₅₀s were 1,000 to 80,000 times higher than the EC₅₀ of 17β‐oestradiol. Bisphenol A and 4‐hydroxybiphenyl induced cell growth in MCF‐7 cells, and the highest test concentrations induced responses, apparently exceeding the cell growth induced by 17β‐oestradiol. The other chemicals tested induced less than 50% of the maximum 17β‐oestradiol‐stimulated cell growth. Bisphenol A, 4‐hydroxybiphenyl, tetrabromobisphenol A and tetrachlorobisphenol A all increased the level of the oestrogen‐regulated proteins, progesterone receptor and pS2, whereas 4,4′‐dihydroxybiphenyl showed no such effect. Bisphenol A was the only chemical tested that clearly mimicked 17β‐oestradiol in its ability to reduce the level of cytosolic oestrogen receptors in MCF‐7 cells. By measuring several oestrogen‐dependent endpoints it seems that some xeno‐oestrogens cause an imbalanced oestrogen‐response. Their ability and potency in mimicking 17β‐oestrogen in one parameter is not necessarily accompanied by a similar effect in another oestrogen‐linked parameter.     

New indolicidin analogues with potent antibacterial activity*

Abstract: Indolicidin is a 13‐residue antimicrobial peptide amide, ILPWKWPWWPWRR‐NH₂, isolated from the cytoplasmic granules of bovine neutrophils. Indolicidin is active against a wide range of microorganisms and has also been shown to be haemolytic and cytotoxic towards erythrocytes and human T lymphocytes. The aim of the present paper is two‐fold. First, we examine the importance of tryptophan in the antibacterial activity of indolicidin. We prepared five peptide analogues with the format ILPXKXPXXPXRR‐NH₂ in which Trp‐residues 4,6,8,9,11 were replaced in all positions with X = a single non‐natural building block; N‐substituted glycine residue or nonproteinogenic amino acid. The analogues were tested for antibacterial activity against both Staphylococcus aureus American type culture collection (ATCC) 25923 and Escherichia coli ATCC 25922. We found that tryptophan is not essential in the antibacterial activity of indolicidin, and even more active analogues were obtained by replacing tryptophan with non‐natural aromatic amino acids. Using this knowledge, we then investigated a new principle for improving the antibacterial activity of small peptides. Our approach involves changing the hydrophobicity of the peptide by modifying the N‐terminus with a hydrophobic non‐natural building block. We prepared 22 analogues of indolicidin and [Phe^4,6,8,9,11] indolicidin, 11 of each, carrying a hydrophobic non‐natural building block attached to the N‐terminus. Several active antibacterial analogues were identified. Finally, the cytotoxicity of the analogues against sheep erythrocytes was assessed in a haemolytic activity assay. The results presented here suggest that modified analogues of antibacterial peptides, containing non‐natural building blocks, are promising lead structures for developing future therapeutics.     

Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.

PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.