A response to "Concepts in malignant transformation" - a pathologists perspective.

The publication by Brendan Bebington entitled "Concepts in malignant transformation" was a thought provoking article. The article theorises that the process of aging, as a consequence of programmed cellular events, will result in death, which is essential for survival of the population. The theory then expands to suggest that eukaryotic cells have retained an epigenetic ability to enable demise of the organism via cell-determined origin for events like aging and malignant transformation. The author suggests that "cancer may be a de-suppression of an ancient epigenetic instruction" and "malignancy has become an evolutionary advantage, even though it may be disadvantageous to the individual".

Art, nature and mental health: assessing the biopsychosocial effects of a 'creative green prescription' museum programme involving horticulture, artmaking and collections.

AIMS: To assess the biopsychosocial effects of participation in a unique, combined arts- and nature-based museum intervention, involving engagement with horticulture, artmaking and museum collections, on adult mental health service users. METHODS: Adult mental health service users (total n = 46 across two phases) with an average age of 53 were referred through social prescribing by community partners (mental health nurse and via a day centre for disadvantaged and vulnerable adults) to a 10-week 'creative green prescription' programme held in Whitworth Park and the Whitworth Art Gallery. The study used an exploratory sequential mixed methods design comprising two phases - Phase 1 (September to December 2016): qualitative research investigating the views of participants (n = 26) through semi-structured interviews and diaries and Phase 2 (February to April 2018): quantitative research informed by Phase 1 analysing psychological wellbeing data from participants (n = 20) who completed the UCL Museum Wellbeing Measure pre-post programme. RESULTS: Inductive thematic analysis of Phase 1 interview data revealed increased feelings of wellbeing brought about by improved self-esteem, decreased social isolation and the formation of communities of practice. Statistical analysis of pre-post quantitative measures in Phase 2 found a highly significant increase in psychological wellbeing. CONCLUSION: Creative green prescription programmes, using a combination of arts- and nature-based activities, present distinct synergistic benefits that have the potential to make a significant impact on the psychosocial wellbeing of adult mental health service users. Museums with parks and gardens should consider integrating programmes of outdoor and indoor collections-inspired creative activities permitting combined engagement with nature, art and wellbeing.

Fatty acids in plasma and red cell membranes in normal humans.

A detailed study was made of the fatty acid composition of plasma triglycerides, free fatty acids, phospholipids, red cell total phospholipids, phosphatidylcholine and phosphatidylethanolamine in 32 normal males and 18 normal females. No sex differences could be detected. There were substantial differences in the compositions of the various fractions and long-chain polyunsaturated fatty acids were particularly important in the red cells.

The influence of dietary manipulation with n-3 and n-6 fatty acids on liver and plasma phospholipid fatty acids in rats.

The interrelations between linoleic acid (LA) metabolites and fish oil fatty acids were studied. Sprague-Dawley rats (200-220 g) were fed a fat-free semisynthetic diet supplemented with 10% (by weight) of different combinations of evening primrose oil (EPO), a rich source of LA and gamma-linolenic acid, and polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The combinations of supplement were as follows: 9% EPO-1% POL, 8% EPO-2% POL, 7% EPO-3% POL, 6% EPO-4% POL and 5% EPO-5% POL. After two weeks on the respective diets, the animals were killed, and the fatty acid compositions of liver and plasma phospholipids were examined. The results showed that animals fed higher proportions of POL consistently contained higher levels of dihomo-gamma-linolenic acid (DGLA) (p less than 0.05), a metabolite of LA and GLA, and lower levels of arachidonic acid (AA) (p less than 0.01), a metabolite of DGLA through delta-5-desaturation. Thus, an inverse relationship between AA/DGLA ratio and EPA levels was found to exist (r = -0.765 in plasma and -0.792 in liver). However, there was no such relationship between AA/DGLA ratio and DHA levels. This result suggested that EPA but not DHA in fish oil exerts an inhibitory effect on the conversion of DGLA to AA.

Plasma, platelet, and aorta fatty acids composition in response to dietary n-6 and n-3 fats supplementation in a rat model of non-insulin-dependent diabetes.

Male Sprague-Dawley rats were injected with 90 mg/kg of streptozotocin at 2 days of age. After weaning, they were put on a fat-free diet supplemented with safflower oil (S), a combination of S and linseed oil (L) or a combination of evening primrose oil (E) and L for 8 weeks. Plasma glucose levels and glycosuria were significantly elevated in all 3 groups of diabetic rats in comparison with the corresponding control rats. The percentage of arachidonic acid (20:4n-6) in plasma phospholipids of the S + L and E + L groups was similar to that of the S group and did not differ between control and diabetic rats while adrenic acid (22:4n-6) and docosahexaenoic acid (22:6n-3) changed in proportion to dietary n-3 and n-6 fats content. Arachidonic acid in aorta phospholipids significantly reduced in all 3 groups of diabetic rats as compared to the corresponding control groups. Dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid in aorta phospholipids increased by the E + L treatment. These results suggest that arachidonic acid in plasma phospholipids is kept constant regardless of the presence of diabetes of non-insulin-dependent type or dietary n-3 and n-6 fats supplementation. In aorta phospholipids, arachidonic acid in diabetic animals reduced and this may be compensated by gamma-linolenic acid supplementation, which leads to increase of dihomo-gamma-linolenic acid and arachidonic acid levels.

Point of care technology: impact on people and paperwork.

A systematic evaluation of a bedside computer system for nursing documentation indicates that point of care technology has a positive direct impact on the efficiency, effectiveness, and satisfaction of the nursing staff, and a positive indirect influence on other members of the health care team in their delivery of patient care.

A meta-analysis of blood fatty acids in people with learning disorders with particular interest in arachidonic acid.

Small individual studies report that people with learning disorders have lower than normal blood concentrations of docosahexaenoic acid and arachidonic acid. The origin and consequence of the subnormal docosahexaenoic acid have been much speculated. However, relatively little attention has been paid to the significance of the low arachidonic acid concentration. Studies were identified through a literature search including subjects with various learning disorders or symptoms thereof and age-matched controls. A meta-analysis of pooled data from the red blood cell and plasma/serum showed that red blood cell arachidonic acid and docosahexanoic acid concentrations were significantly lower than normal [-3.93 and -18.92, respectively (weighted mean difference as a % of weighted mean control)]. Plasma/serum arachidonic acid and docosahexaenoic acid concentrations were also significantly lower than normal [-6.99 and -15.66, respectively (weighted mean difference as a % of weighted mean control)]. However, in absolute amounts the arachidonic acid was as severely depressed as docosahexanoic acid within red blood cells 0.57mg/100mg of fatty acid below normal verses 0.59mg/100mg for docosahexaenoic acid. Plasma/serum arachidonic acid was even lower; 0.71mg/100mg of fatty acid below normal verses 0.34mg/100mg for docosahexaenoic acid. The origin, consequences and relative importance of subnormal arachidonic acid to brain function bears further investigation.

A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries?

UNLABELLED: The global incidence of atopic eczema is escalating. While new treatment options are becoming available, previous treatments with certain confirmed benefits are still worth investigating as safe and effective therapies. One such treatment, Efamol evening primrose oil (EPO), was proven efficacious in a 1989 meta-analysis of randomized, double-blind, placebo-controlled clinical trials. A decade of further testing and subsequent independent reanalysis of 26 clinical studies including 1207 patients presented here, establishes that Efamol EPO has a simultaneous, beneficial effect on itch/pruritus, crusting, oedema and redness (erythema) that becomes apparent between 4 and 8 weeks after treatment is initiated. However, the magnitude of this effect is reduced in association with increasing frequency of potent steroid use. This and other confounding variables that are now being reported in the literature may account for historically reported inconsistent patient response. Recent research has uncovered unique complexities in fatty acid metabolism and immune response in the atopic condition beyond those previously reported and may well have identified a subcategory of non-responders and has helped established those that can consistently derive significant benefit. Further research is needed to provide a better understanding of the physiology behind this complex disorder and the beneficial role that fatty acids can play in its development and management. CONCLUSION: Efamol EPO has a simultaneous, beneficial effect on itch/pruritus, crusting, oedema and redness (erythema) that becomes apparent between 4 and 8 weeks after treatment is initiated. However, the magnitude of this effect is reduced in association with increasing frequency of potent steroid use.

Essential fatty acids in plasma of patients with leprosy.

We have investigated the fatty-acid composition of plasma phospholipids in 61 patients with leprosy of various clinical types with either a short or long duration of treatment. All patients had significantly decreased levels of linoleic acid and alpha-linoleic acid, the parent fatty acids of the n-6 and n-3 families, respectively. Patients with a treatment duration of more than 6 months had significantly low levels of arachidonic acid and eicosapentaenoic acid compared to controls or to patients with a treatment duration of less than 6 months. There were no differences in the fatty-acid composition between multibacillary patients and paucibacillary patients. We conclude that dietary supplementation with essential fatty acids may be indicated in patients with leprosy, particularly in those with a long treatment duration.

Essential fatty acids in the plasma phospholipids of patients with atopic eczema.

We have measured all the essential fatty acids (EFA) in plasma phospholipids in forty-one adults with atopic eczema and fifty normal controls. The major dietary n-6 EFA, linoleic acid, was significantly elevated, but all its metabolites, 18:3n-6, 20:3n-6, 20:4n-6, 22:4n-6, and 22:5n-6 were significantly reduced. The major dietary n-3 EFA, alpha-linolenic acid, was also elevated, though not significantly, while all its metabolites were also significantly reduced. These observations suggest that atopic eczema is associated not with any defect of EFA intake, but with abnormal metabolism, possibly involving the enzyme delta-6-desaturase. Treatment with oral evening primrose oil produced partial correction of the n-6 EFA abnormality, but had no effect on the n-3 EFAs.

Breast milk from mothers of children with newly developed atopic eczema has low levels of long chain polyunsaturated fatty acids.

BACKGROUND: Infants at risk of atopic dermatitis have lower than normal levels of long chain polyunsaturated fatty acids. These fatty acids are normally present in substantial quantities in human breast milk. METHODS: Because of the equivocal evidence concerning the ability of breastfeeding to delay the onset or reduce the severity of atopic dermatitis, we have analyzed the fatty acid composition of breast milk from the mothers of children with newly developed disease with the use of gas chromatography. RESULTS: Breast milk lipids from mothers of children with newly developed atopic dermatitis had increased proportions of linoleic acid and significantly decreased proportions of its long chain polyunsaturated derivatives compared with a control group. The ratio of linoleic acid to the sum of its metabolites, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid was 11.78 in the atopic group and 9.02 in the control group (p < 0.01). CONCLUSIONS: These results are consistent with previous findings of an abnormal fatty acid status in atopic subjects and may account for some of the inconsistent results from studies of the effect of breastfeeding on the subsequent development of atopic dermatitis. We conclude that further studies to examine the effects of supplementation of the diet of breastfeeding mothers with long chain polyunsaturates should be done.

Plasma essential fatty acids in pure and mixed race American Indians on and off a diet exceptionally rich in salmon.

Eskimos on a traditional diet have unusually low prevalences of cardiovascular disease and cancer. One possible reason is the high intake of eicosapentaenoic acid (EPA) which is thought to account for the high EPA and low arachidonic acid (AA) levels in Eskimo plasma. People who also consume a traditional diet exceptionally rich in EPA are the Indians of the west coast of Vancouver Island. There are about 12,000 of these people and their traditional diet has been affected much less than that of the Eskimos. When on their traditional diet the Vancouver Island Indians, like the Eskimos, have high EPA and low AA levels in plasma. When eating European food, EPA levels are in the European range, but AA levels are still exceptionally low, a finding also reported from Eskimos living in Denmark. In a small mixed race group, AA levels were intermediate between those in pure Indians and in Europeans. The high EPA levels in Eskimos and West Coast Indians are related to diet. The low AA levels, in contrast, are probably genetically determined. Unusual disease patterns in these populations cannot be entirely attributed to diet.

Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy.

In the plasma phospholipids of a group of 50 young adults with atopic eczema, there was an elevation of cis-linoleic acid associated with a deficit of gamma-linolenic acid and of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. This suggests that atopics have a deficit in the function of the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. Carriers of cystic fibrosis tend to be phenotypically atopic, supporting previous suggestions that in homozygote cystic fibrosis patients the key defect may be in the delta-6-desaturase enzyme. Atopic patients may be exceptionally sensitive to side effects of non-steroidal anti-inflammatory agents. They fail to flush in response to application of niacin compounds to the skin, a reaction mediated by prostaglandins. A deficit of prostaglandin precursors would explain both of these observations. That the observed biochemical deficit plays a causative role in the manifestations of atopy was indicated by the fact that in a double-blind, placebo-controlled crossover trial, gamma-linolenic acid in the form of evening primrose oil (Efamol), partially corrected both the biochemical abnormalities and the clinical state.