Anything in modulation?

This issue of Annals of Oncology sees a report of a trial bythe Italian INTACC intergroup comparing folinic acid-modulatedfluorouracil, combined with levamisole, with fluorouracil andlevamisole alone [1]. This large trial (n = 1703) adds importantlyto our knowledge of the value of folinic acid in the fluorouracil/folinicacid (FUFA) chemotherapy combination, which is now widely acceptedas the standard regimen in colorectal cancer [2]. No statisticallysignificant differences in terms of disease-free survival oroverall survival were found from modulating the action of fluorouracilwith folinic acid. However, the absence of a statistically significantdifference does not of course establish lack of benefit. Therewere fewer deaths (32%     

The biomechanics of restricted movement in adult obesity

In spite of significant advances in the knowledge and understanding of the multi-factorial nature of obesity, many questions regarding the specific consequences of the disease remain unanswered. In particular, there is a relative dearth of information pertaining to the functional limitations imposed by overweight and obesity. The limited number of studies to date have mainly focused on the effect of obesity on the temporospatial characteristics of walking, plantar foot pressures, muscular strength and, to a lesser extent, postural balance. Collectively, these studies have implied that the functional limitations imposed by the additional loading of the locomotor system in obesity result in aberrant mechanics and the potential for musculoskeletal injury. Despite the greater prevalence of musculoskeletal disorders in the obese, there has been surprisingly little empirical investigation pertaining to the biomechanics of activities of daily living or into the mechanical and neuromuscular factors that may predispose the obese to injury. A better appreciation of the implications of increased levels of body adiposity on the movement capabilities of the obese would afford a greater opportunity to provide meaningful support in preventing, treating and managing the condition and its sequelae. Moreover, there is an urgent need to establish the physical consequences of continued repetitive loading of major structures of the body, particularly of the lower limbs in the obese, during the diverse range of activities of daily living.     

Surfactant approach to the gastric mucosal barrier: protection of rats by banana even when acidified

Physical studies of their suspensions have shown bananas to be highly surface active at both liquid-air and solid-liquid interfaces which they render hydrophobic by adsorption of phospholipid detected by thin-layer chromatography and by staining. Electron microscopy of the fruit has demonstrated lamellar bodies--the same form in which phospholipid is so surface-active in the lung. When administered to intact rats and scored by two methods (ulcer length and area), banana imparted appreciable (75%) protection against acid insult (1 ml of 0.8 N HCl) in a dose-dependent manner not attributable to "bulking" or buffering as it was equally effective at a pH of 2. The best protection (89% by ulcer length) was obtained with banana vortexed with milk (1:1), this mixture offering the possibility of a simple foodstuff on which to maintain patients treated acutely by suppressing acid secretion pharmacologically. These studies support Davenport's original concept of a gastric mucosal barrier--but one whose physical reality is provided by an adsorbed layer of surface-active phospholipid (surfactant).     

Missed opportunities for the prevention of cardiovascular disease among British hypertensives in primary care.

BACKGROUND: High-risk strategies for the prevention of cardiovascular disease (CVD) among hypertensive patients require knowledge of the prevalence and interaction of modifiable risk factors to ensure effective targeting of interventions. Comparatively little is known of risk-factor profiles and their modification among hypertensives in primary care. AIM: The present study was designed to explore relationships between patients' knowledge of CVD risk factors, their perception of personal risk and health behaviours, and their use of lifestyle interventions. METHOD: A cross-sectional survey of 2676 men and women with mild to moderate hypertension (diastolic blood pressure 95-115 mmHg), and their general practitioners, recruited from 1044 general practices throughout the UK, was conducted. RESULTS: Levels of modifiable risk factors were high, although there was considerable variation by age and sex; most (98.5%) patients had at least one additional CVD risk factor. A lower standard of living was associated with a higher prevalence of 'unhealthy' behaviours. Out of those with a current lifestyle problem, 85% of obese patients, 59% of smokers, 47% of excess drinkers, 49% of those with dietary risk factors and 32% of inactive patients claimed to have adopted healthier behaviours within the past 3 months. Older subjects and those with a lower standard of living were less likely to acknowledge risks, and those who did were less likely to report improving their lifestyles. While 71% of patients recalled receiving lifestyle advice, the coverage and targeting of specific interventions was generally poor. Overall, 60% of the sample had received advice on weight control, 47% on diet, 38% on exercise, 38% on smoking and 36% on alcohol. Women and older people were less likely to be given relevant counseling, and there was no evidence of targeting with respect to subjects' social class, level of hypertension or duration of diagnosis. CONCLUSION: Lifestyle interventions are welcomed and are viewed as helpful by patients receiving them. Potential health gains among high-risk hypertensives are being lost because of poor targeting and coverage of those at greatest risk.     

T cells and protective immunity to Plasmodium berghei in rats.

Experiments were carried out in which unfractionated spleen cells, and T lymphocyte subpopulations characterized by certain experimental criteria, were isolated at various times from rats infected with Plasmodium berghei. By adoptive transfer it was shown that unfractionated spleen cells, and T cells alone, could transfer protection to syngenic recipients as early as 11 days after infection of the cell donors. The protection conferred by T cells increased with the duration of the infection in the donors, at least up to 100 days. The additional presence of B cells in transferred lymphocyte populations enhanced their protective capacity over that shown by T cells alone. The role of T cells in protective immunity to malaria is discussed.     

Bone histology in young adult osteoporosis.

Bone histology was quantitated in 10 osteoporotic patients aged between 17 and 51 years and in six healthy subjects aged between 23 and 43 years. The osteoporosis was of varying aetiology and was clinically stable. All patients were given tetracycline before biopsy and double tetracycline labelling was used in seven patients. Bone forming and resorbing surfaces were defined by the presence of osteoblasts and osteoclasts, respectively, which were identified by histochemical techniques. The associations between bone forming and resorbing surfaces were similar in patients and controls, though the range of values was wider in the patients than in the controls. Mineral apposition rate was normal in the osteoporotic patients, but there was a reduction in mineralising (tetracycline) surface, whether related to osteoid surface or to osteoblast surface. This did not indicate osteomalacia as the directly and indirectly measured mineralisation lag times were normal. The osteoid seams were thinner in osteoporotic patients than in controls. The data suggest that osteoclast and osteoblast numbers were normal in this group of osteoporotic patients but that the metabolic activity of osteoblasts was impaired.     

A hydrophobic oligolamellar lining to the vascular lumen in some organs.

Various endothelial surfaces from sheep and humans have been studied for their hydrophobicity using a standard method based on the angle of contact (theta) of the surface with a droplet of saline placed on it. Most surfaces were relatively hydrophilic (theta less than 25 degrees) but some were distinctly hydrophobic with theta exceeding 65 degrees for sheep pulmonary vein, left ventricle, and aorta, and human umbilical vein. These results are discussed as compatible with the theory that surface-active phospholipid (surfactant) migrates from lung tissue into the pulmonary circulation or reaches intravascular sites from other sources. Transmission electron microscopy of cerebral vessels demonstrated an oligolamellar lining of surfactant on many endothelial surfaces, bridging the "tight" junctions between endothelial cells in many cases. Lamellar bodies were found adjacent to the endothelium. The oligolamellar surfactant lining and lamellar bodies are discussed as potentially very important factors in influencing bubble formation on vessel walls. It is believed to impart hydrophobicity while it could also determine the microgeometry of any crevices vital for bubble formation or retention.     

Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists.

PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.