Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

Antitumour imidazotetrazines XXVIII 3-methyladenine DNA glycosylase activity in cell lines sensitive and resistant to temozolomide.

The ability of extracts of a range of cell lines to release methylated bases from a DNA substrate, which had been modified with [3H]dimethyl sulphate, has been compared in cell lines with differing sensitivity to the cytotoxic drug, temozolomide. High performance liquid chromatography profiles of the bases released by these extracts showed that the activity was specific for 3-methyladenine. There was little variation in the level of 3-methyladenine-DNA glycosylase between the different cell lines despite a 40-fold difference in sensitivity to temozolomide and no correlation with the level of O6-alkylguanine-DNA alkyltransferase.     

Weight loss in a murine cachexia model is not associated with the cytokines tumour necrosis factor-alpha or interleukin-6.

Daily administration of an escalating dose of tumour necrosis factor-alpha (TNF-alpha) to female NMRI mice caused a progressive loss of body weight representing 12% of the original weight over a 6-day period. Weight loss was associated with a decreased food intake and pair-fed controls exhibited a weight loss of similar magnitude to that caused by TNF-alpha. However, weight loss in animals bearing a murine adenocarcinoma (MAC16) occurred without a change in energy intake and thus differed from that produced by TNF-alpha. Anti-TNF-alpha monoclonal antibodies at levels capable of protecting mice against lethal endotoxaemia were ineffective in reversing weight loss in animals bearing the MAC16 tumour and had no effect on the increase in tumour volume. Circulating levels of interleukin-6 were not elevated in animals bearing the MAC16 tumour and with a weight loss between 1.8 and 5.4 g. These results suggest that these cytokines are not involved in the cachexia produced by this murine tumour.     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Effect of polyunsaturated fatty acids on the growth of murine colon adenocarcinomas in vitro and in vivo.

The effect of the polyunsaturated fatty acids (PUFAs) linoleic acid (LA) and arachidonic acid (AA) on the growth of two murine colon adenocarcinoma cell lines (MAC26 and MAC13) has been determined both in vitro and in vivo. When the serum concentrations in the medium became growth limiting, low concentrations (18-33 microM) of both PUFAs were growth stimulatory to both cell lines, while higher concentrations were growth inhibitory. Growth stimulation by AA in both cell lines, and by LA in MAC13, was effectively inhibited by both the cyclo-oxygenase and lipoxygenase inhibitor indomethacin, and the lipoxygenase inhibitor BWA4C in a dose-dependent manner. The most effective inhibition was exerted by BWA4C, suggesting metabolism of both PUFAs through the lipoxygenase pathway for growth stimulation. In vivo studies using the MAC26 tumour showed a significant stimulation of tumour growth when LA was administered orally at concentrations higher than 0.4 g kg-1 day-1. Higher concentrations did not produce a further increase in tumour growth rate. This suggests that there is a threshold dose for growth stimulation by LA which, together with that in the diet, amounted to 3.8% of the total caloric intake. The increase in tumour volume induced by LA arose from a reduction in the potential doubling time from 41 to 28 h and was effectively reversed by indomethacin (5 mg kg-1). These results suggest that PUFAs may play an important role in tumour growth and may offer a potential target for the development of chemotherapeutic agents.     

A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration

OBJECTIVE: The aim was to establish the potential efficacy, tolerabilityand side-effect profile of electromagnetic therapy as an adjunctto conventional dressings in the treatment of venous leg ulcers. METHOD: A prospective, randomized, double blind controlled clinicaltrial was carried out in a dedicated leg ulcer clinic basedin one urban general practice. Nineteen patients with leg ulcersof confirmed venous aetiology were assessed. The main outcomemeasures were rate and scale of venous leg ulcer healing, changesin patient-reported pain levels, quality of life, degree ofmobility, side effect profile and acceptability to patientsand staff. RESULTS: Sixty-eight per cent of patients attending this dedicated clinicachieved improvements in the size of their ulcer (4, 21%, healedfully) and in reduced pain levels (P < 0.05) during the trial,despite the chronicity of ulcer histories. Patients treatedwith electromagnetic therapy at 800 Hz were found at day 50to have significantly greater healing (P < 0.05) and paincontrol (P < 0.05) than placebo therapy or treatment with600 Hz. All patients reported improved mobility at the end ofthe study. The electromagnetic therapy was well tolerated bypatients, with no differences between groups in reporting adverseevents, and proved acceptable to staff. CONCLUSION: Despite the small numbers in this pilot study, electromagnetictherapy provided significant gains in the healing of venousleg ulcers and reduction in pain. Keywords. Electromagnetic therapy, RCT, leg ulcers, primary care.