Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network

BACKGROUND: The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas. METHODS: We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment began to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments. RESULTS: Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and 584 to the low-fiber group. The median times from randomization to the last follow-up colonoscopy were 34 months in the high-fiber group and 36 months in the low-fiber group. By the time of the last follow-up colonoscopy, at least one adenoma had been identified in 338 subjects in the high-fiber group (47.0 percent) and in 299 subjects in the low-fiber group (51.2 percent). The multivariate adjusted odds ratio for recurrent adenoma in tile high-fiber group, as compared with the low-fiber group, was 0.88 (95 percent confidence interval, 0.70 to 1.11; P=0.28), and the relative risk of recurrence according to the number of adenomas, in the high-fiber group as compared with the low-fiber group, was 0.99 (95 percent confidence interval, 0.71 to 1.36; P=0.93). CONCLUSIONS: As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.     

Bone morphogenesis in implants of residues of radioisotope labelled bone matrix

Bone matrix demineralized in 0.6 N HCl at 2° for 24 h and implanted in muscle in allogeneic rats possesses consistently reproducible bone morphogenetic activity. Experiments on implants of matrix, obtained from donors injected with³H-tyrosine or³H-tryptophan, or Na³⁵SO₄, suggest that bone morphogenetic property is a protein or apart of a protein that is (1) insoluble in buffer solutions, pH 3.6 and 5.0; (2) degraded in buffer solutions at pH 7.4 by an endogenous sulfhydryl-group neutral proteinase; (3) digested by trypsin at 15° within 8 h without solubilization of the helical regions, possibly even without degradation of the nonhelical ends of the bone collagen molecule, and without any loss of the periodic ultrastructure of the collagen fibrils; (4) degraded or removed by 0.1 N NaOH at 2° within 24 h without solubilization of collagen; (5) biologically active even after nitration of tyrosyl groups with tetranitromethane. The release of only one-third of the radioactivity with loss of nearly all yield of new bone by limited tryptic digestion of³H-borohydride-reduced matrix indicates that the bone morphogenetic response is the function of a non-collagenous component. Autoradiographs of implants of matrix with non-collagenous proteins labelled with³H-tryptophan,³H-tyrosine, or both³H-tyrosine and³H-phenyl-alanine demonstrate random dissemination of the radioactive constituents and no evidence of local transfer of labelled proteins or soluble protein derivatives. Hypothetically, the bone morphogenetic response is controlled by an insoluble acidic bone morphogenetic protein or polypeptide (BMP) and a soluble neutral proteinase (BMP-ase) resembling trypsin in activity except functionally more specific for BMP. Firmly bound but separable from bone collagen, BMP is one of many short-lived morphogenetic substances appearing and disappearing throughout embryonic development and persisting in postfetal life. Where the BMP receptor resides and how it activates cell mechanisms of differential repression and derepression of such genes as code for osteogenesis is unknown.     

Mesothelioma possibly due to environmental exposure to asbestos in childhood

Summary A case of diffuse pleural mesothelioma with widespread metastases is described. At first the tumour was thought to be a spontaneous mesothelioma. Later, while watching a television programme on asbestos exposure, the patient remembered living near to an asbestos factory for two years during childhood.     

Relation between physical exertion and heart rate variability characteristics in professional cyclists during the Tour of Spain

Background: Continued exposure to prolonged periods of intense exercise may unfavourably alter neuroendocrine, neuromuscular, and cardiovascular function.

Objective: To examine the relation between quantifiable levels of exertion (TRIMPS) and resting heart rate (HR) and resting supine heart rate variability (HRV) in professional cyclists during a three week stage race.

Method: Eight professional male cyclists (mean (SEM) age 27 (1) years, body mass 65.5 (2.3) kg, and maximum rate of oxygen consumption (V^·O₂MAX) 75.6 (2.2) ml/kg/min) riding in the 2001 Vuelta a España were examined for resting HR and HRV on the mornings of day 0 (baseline), day 10 (first rest day), and day 17 (second rest day). The rest days followed stages 1–9 and 10–15 respectively. HR was recorded during each race stage, and total HR time was categorised into a modified, three phase TRIMPS schema. These phases were based on standardised physiological laboratory values obtained during previous V^·O₂MAX testing, where HR time in each phase (phase I = light intensity and less than ventilatory threshold (VT; ~70% V^·O₂MAX); phase II = moderate intensity between VT and respiratory compensation point (RCP; ~90% V^·O₂MAX); phase III = high intensity (>RCP)) was multiplied by exertional factors of 1, 2, and 3 respectively.

Results: Multivariate analysis of variance showed that total TRIMPS for race stages 1–9 (2466 (90)) were greater than for stages 10–15 (2055 (65)) (p<0.0002). However, TRIMPS/day were less for stages 1–9 (274 (10)) than for stages 10–15 (343 (11)) (p<0.01). Despite a trend to decline, no difference in supine resting HR was found between day 0 (53.2 (1.8) beats/min), day 10 (49.0 (2.8) beats/min), and day 17 (48.0 (2.6) beats/min) (p = 0.21). Whereas no significant group mean changes in HR or HRV indices were noted during the course of the race, significant inverse Pearson product-moment correlations were observed between all HRV indices relative to total TRIMPS and TRIMPS/day accumulated in race stages 10–15. Total TRIMPS correlated with square root of mean squared differences of successive RR intervals (r = –0.93; p<0.001), standard deviation of the RR intervals (r = –0.94; p<0.001), log normalised total power (r = –0.97; p<0.001), log normalised low frequency power (r = –0.79; p<0.02), and log normalised high frequency power (r = –0.94; p<0.001).

Conclusion: HRV may be strongly affected by chronic exposure to heavy exertion. Training volume and intensity are necessary to delineate the degree of these alterations.

     

Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis

HER2 (erbB2/neu) is a member of the erbB family of receptor tyrosine kinases and is involved in regulating the growth of several types of human carcinomas. HER2 represents a successful therapeutic target of the biotechnology era as exemplified by the drug Herceptin (trastuzumab), which has clinical activity in a subset of breast cancer patients. Using DNA microarrays, we identified a cohort of genes that are differentially regulated by HER2 in breast epithelial cells. One of the HER2-regulated genes discovered was fatty acid synthase (FAS), which has been shown to be overexpressed in breast cancer as well as other cancers. FAS is implicated in tumorigenesis through its role in cell proliferation and membrane lipid incorporation of neoplastic cells. Here, we demonstrate that HER2-mediated induction of FAS is inhibitable by Herceptin and tyrosine kinase inhibitors of HER2. Through a phosphatidylinositol 3'-kinase-dependent pathway, HER2 stimulates the FAS promoter and ultimately mediates increased fatty acid synthesis. Interestingly, pharmacological inhibition of FAS preferentially induced apoptosis of HER2-overexpressing breast epithelial cells relative to matched vector control cells. These studies characterize a molecular connection between two genes individually implicated in tumorigenesis but never linked together.     

Ecthyma gangraenosum--a trap for the unwary

Neutropaenic patients are at particular risk of developing a pseudomonal fasciitis known as ecthyma gangraenosum. Despite the similarities with necrotising fasciitis, Fournier's gangrene has a very different aetiology and management.     

Review of common adverse effects of selected antiarrhythmic drugs

The management of cardiac arrhythmias has changed dramatically over the past several years. New drugs and devices are now available to treat various arrhythmias. Many new agents have been developed that rely on different electrophysiologic mechanisms to elicit their effect on the heart rhythm. Though often effective, these drugs also pose a risk because all of them have a variety of potential adverse effects associated with their use. Many of these adverse reactions are common to all antiarrhythmic drugs, whereas others are unique to particular agents. This review discusses the notable adverse effects of selected antiarrhythmic drugs.