Reduction of colonic carcinogenesis by wheat bran independent of fecal bile acid concentration

It has been reported previously that populations with a decreased concentration of fecal bile acids have a lower incidence of colon cancer. We examined the importance of fecal bile acid dilution by wheat bran (WB) in inhibiting colonic tumorigenesis in an experimental animal model. Male F344 rats received oral doses of the colon carcinogen 1,2-dimethylhydrazine [CAS: 540-73-8] and were assigned randomly to groups fed one of four semipurified diets for 26 weeks. The diets were fiber-free (FF), 10% WB, FF + bile salts, or WB + bile salts. The amount of bile salts added was adjusted to produce a fecal bile acid concentration in the group fed WB + bile salts equal to that found in the FF groups. Fecal bile acid concentrations at 12 and 24 weeks in the WB + bile salts group were similar to those in the FF group. Gross and microscopic findings at necropsy revealed a reduced total number and multiplicity of colon tumors in both bran-fed groups. Although the fecal bile acid concentrations of the FF and WB + bile salts groups were equal, the latter showed a significant reduction in tumor yield.     

Influence of meal distribution of wheat bran on fecal bulk, gastrointestinal transit time and colonic thymidine kinase activity in the rat

Male Fischer 344 rats were fed either fiber-free (FF), continuous 10% wheat bran (CWB) or intermittent 50% wheat bran (IWB) diets for 6 wk to investigate possible alterations in physiological effects associated with colon cancer (fecal bulk, transit time, colonic cell proliferation) induced by meal distribution of the bran. The FF and CWB groups consumed unvaried diets throughout the day. The IWB group consumed two consecutive meals of a 50% bran diet for a total of 4 hr each day followed by a fiber-free diet for the remaining hours of the day. Similar daily quantities of bran were consumed in the CWB and IWB groups. Dry fecal weights rose significantly and transit times declined in both bran-fed groups independent of the meal distribution of bran. Colonic cell proliferation (estimated by thymidine kinase activity) was similar in all groups. The results suggest that these physiological effects of wheat bran are independent of the meal distribution of the bran.     

Geriatric trauma: resource use and patient outcomes.

INTRODUCTION: Elderly patients who suffer trauma have a higher mortality and use disproportionately more trauma resources than younger patients. To compare these 2 groups and determine the outcomes and characteristics of elderly patients, we reviewed patients in these 2 groups admitted and treated in our tertiary care provincial trauma centre. METHODS: From the provincial trauma registry we selected a cohort of 40 geriatric patients (group 1) (> or = 65 yr of age) with an ISS of 16 or more who were admitted to and spent time in our trauma service for more than 48 hours and compared them with a similar randomly selected cohort of 44 patients (group 2) aged 20-30 years. Family physicians were contacted for follow-up of these patients 2 years after discharge. We considered length of hospital stay, complications, disposition of the patients and use of consultation services. RESULTS: Patients in group 1 had a mean age of 72.1 years (range from 65-98 yr) and a mean ISS of 27.3 (range from 17-50). Patients in group 2 had a mean age of 26.3 years (range from 22-29 yr) and a mean ISS of 26.3 (range from 17-54). Hospital stay was significantly longer in the group 1: 34.5 days (95% confidence interval [CI]: 24-44 d) versus 21.6 days (95% CI: 15-28 d). More elderly patients experienced complications (35 v. 13, p < 0.001) and required medical consultations (35 v. 26, p < 0.001). In-hospital death rates were 8% (3 of 40) and 4% (2 of 44) respectively (p = 0.3). Fewer geriatric patients could be discharged home (35% [14 of 40] v. 27% [22 of 44], p = 0.056) or to rehabilitation facilities (28% [11 of 40] v. 34% [15 of 44], p = 0.3). Five geriatric patients were discharged to nursing homes (p = 0.007). Of the geriatric patients discharged to rehabilitation facilities or home, 75% were independent 2 years after discharge. CONCLUSIONS: Aggressive care for geriatric trauma patients is warranted, and resources should be directed toward rehabilitation. Based on our findings, we expect that creating a directed care pathway for these patients, targetting complications and earlier discharge, will further improve their outcomes.     

Human lymphoblastoid cells with acquired resistance to C2-desamino-C2-methyl-N10-propargyl-5,8-dideazafolic acid: a novel folate-based thymidylate synthase inhibitor.

We describe the characterization of human lymphoblastoid cell lines with acquired resistance (greater than 20,000-fold) to a novel folate-based thymidylate synthase (TS) (EC 2.1.1.45) inhibitor, C2-desamino-C2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI198583). This acquired resistance was associated with a 64-fold amplification of the TS gene, a similar elevation in the corresponding mRNA, and an approximately 200-fold increase in both TS activity and TS protein. This amplification was maintained when the cells were grown in the absence of the selective agent, ICI198583, for 340 generations. TS isolated from one of the resistant cell lines, W1-L2:C1, displayed inhibition kinetic parameters similar to those of TS isolated from the parent W1-L2 cell line. It thus appears unlikely that resistance is due to an altered TS enzyme having a lower affinity for ICI198583. The resistant cell line, W1-L2:C1, was cross-resistant to other folate-based TS inhibitors but was as sensitive as the parent cell line, W1-L2, to 5-fluorodeoxyuridine. The W1-L2:C1 cell line was collaterally sensitive to the classical dihydrofolate reductase (EC 1.5.1.3) inhibitor methotrexate as well as to the lipophilic dihydrofolate reductase inhibitors metoprine and 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazolin e glucuronic acid salt (also called trimetrexate). When the W1-L2 and W1-L2:C1 cell lines were exposed to 1 microM ICI198583 for 24 h they accumulated the same concentration of total cellular ICI198583 polyglutamates despite the fact that the latter cell line accumulated a 300-fold greater concentration of ICI198583 monoglutamate. As polyglutamates, the tetra- and pentaglutamate forms predominated in the W1-L2 cell line, whereas the diglutamate form predominated in the W1-L2:C1 cell line, with few higher polyglutamates being detected. The lack of tri- and higher polyglutamates of ICI198583 (i.e., the more active species) in the W1-L2:C1 cell line may also contribute to the observed resistance. These findings may have important implications in light of the rapid onset of resistance to antifolates in the clinic.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Rupture of the posterior tibial tendon: CT and surgical findings

Computed tomography (CT) was performed in 42 patients with 49 clinically suspected tears of the posterior tibial tendon. Twenty-eight of the 49 suspected tears were subsequently surgically explored and repaired. Three patterns of tendon abnormalities were recognized on CT scans: type I-intact, hypertrophied, heterogeneous tendon; type II-attenuated tendon; and type III-absence of a portion of a tendon. Types I and II correlated with partial rupture seen during surgery, and type III correlated with complete rupture of the tendon. CT findings were accurate in 96% of the patients who underwent surgery. In four cases (14%), tendon rupture was seen on CT scans, but the extent of the injury was underestimated and the rupture was misclassified. Reactive periostitis of the distal tibia was seen in 71% of diseased tendons and may represent an important factor in the diagnosis of tendon rupture.     

Effects of graded levels of high-molecular-weight carrageenan on colonic mucosal thymidine kinase activity.

Graded levels of high-molecular-weight carrageenan were fed to male Fischer 344 rats to investigate the effects of carrageenan on colonic cell proliferation. Four groups of 7 rats consumed diets containing 0 (control), 0.65, 1.31, or 2.61% carrageenan ad libitum for 4 wk. These levels were designed to simulate (on a milligram-per-kilogram basis) 25, 50, and 100 times the maximal human carrageenan intake. After an overnight fast, the rats were anesthetized, and the colonic mucosa was removed and homogenized. A supernatant was prepared and assayed for total protein and thymidine kinase activity (a marker for cell proliferation). Increasing levels of carrageenan resulted in stepwise increases in total mucosal protein and in thymidine kinase specific (units per milligram of protein) and total (units per centimeter of colon) activity. However, increases in thymidine kinase activity were statistically significant only at the highest dose of carrageenan. No histological abnormalities were associated with any level of carrageenan feeding. These results suggest a clear dose-response increase in colonic mucosal cell proliferation with increasing doses of carrageenan; however, the effect at doses approximating 19 times maximal human intake was not statistically different from that for control rats under the conditions of this study.     

Sweat gland response to exercise in the heat among pre-, mid-, and late-pubertal boys.

Sweating rate (SR) of boys is lower than that of men. To assess the association between the response of individual sweat glands and physical growth and maturation, three groups of circumpubertal boys cycled at 50% VO2max in a climatic chamber (42 degrees C, 20% relative humidity). Based on Tanner staging (pubic hair), 16 were classified as prepubertal (PP, Tanner 1), 15 as midpubertal (MP, Tanner 2-4), and five as late-pubertal (LP, Tanner 5). Population density (PD) of the heat-activated sweat glands, the mean area of sweat drops (DA), and the proportion of skin covered by sweat (%A) were measured by skin photography and computer-assisted imaging analysis. Other measurements included rectal and skin temperatures (Tre, Tsk, respectively), heart rate (HR), and total body SR. The rise in HR, Tre and Tsk did not differ among groups. Whole body SR was significantly higher in the LP group compared with PP (PP = 4.95 +/- 0.23, MP = 5.79 +/- 0.20, LP = 6.70 +/- 0.42 ml.min-1.m-2) (mean +/- SEM). PD was significantly higher in the PP group (PP = 128 +/- 8, MP = 97 +/- 9, LP = 74 +/- 9 glands.cm-2), while DA was higher in the LP group (PP = 5.47 +/- 0.59, MP = 6.92 +/- 0.47, LP = 12.83 +/- 1.41 microns2.10(4)). %A did not differ among groups. The calculated SR per gland was higher among the LP groups compared with the less mature ones (PP = 4.6 +/- 0.3, MP = 7.2 +/- 0.8, LP = 9.6 +/- 1.0 nl.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)