Effects of epidermal growth factor and dimethylhydrazine on crypt size, cell proliferation, and crypt fission in the rat colon. Cell proliferation and crypt fission are controlled independently

Crypt fission is now established as an important mechanism of intestinal growth and regeneration. It has been proposed that increased crypt size is the stimulus for crypt fission, because crypts preparing for fission are generally larger. Consequently, we investigated the effects of epidermal growth factor (EGF) and dimethylhydrazine, which are both known to stimulate crypt cell proliferation, on crypt fission in the rat intestine. We also examined whether the effects of EGF on both proliferation and crypt fission are modified by the pretreatment with dimethylhydrazine for 16 weeks, dimethylhydrazine was then discontinued for 8 weeks, followed by intravenous infusion of EGF for 1 week. There were four groups: vehicle alone, EGF alone, dimethylhydrazine alone, and dimethylhydrazine followed by EGF infusion. The rats were killed at 25 weeks and rates of intestinal crypt cell production, crypt size, and crypt fission were determined. Intravenously infused EGF significantly increased crypt cell production rate, but the magnitude of the effect decreased from the proximal to the distal colon. EGF caused an increase in crypt area, possibly reflecting an increase in crypt size. Importantly dimethylhydrazine had no significant effect on crypt cell production rate nor on crypt area in the distal colon, but it did cause an increase in crypt area in the mid-colon. The crypt fission index was significantly decreased by EGF and increased by dimethylhydrazine. There was no qualitative interaction between EGF and dimethylhydrazine. These results demonstrate the marked proliferative effect of intravenously infused EGF in the colon of orally fed rats, with significant site effects (P = 0.0007); the effect was greatest in the proximal colon and disappeared in the distal colon. The observation that EGF reduced crypt fission indicates that increased cell proliferation, per se, is not a stimulus for crypt fission. This is further supported by the observation that dimethylhydrazine increases crypt fission in crypts of normal size in the distal colon without significantly increasing cell proliferation. These results suggest that increasing crypt cellularity by proliferation is not sufficient to induce crypt fission, and factors other than increased crypt size by proliferation can control crypt fission. It is also probable that cell proliferation and crypt fission are independently regulated. Crypt fission appears to play a considerable role in the intestinal response to carcinogens.     

Evaluating the potential cost-effectiveness of stenting as a treatment for symptomatic single-vessel coronary disease. Use of a decision-analytic model

BACKGROUND: Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease. METHODS AND RESULTS: We developed a decision-analytic model to predict quality-adjusted life expectancy and lifetime treatment costs for patients with symptomatic, single-vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or conventional angioplasty (PTCA). Estimates of the probabilities of overall procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%; PSS, 20%) were derived from review of the literature published as of September 1993. Procedural costs were based on the true economic (ie, variable) costs of each procedure at Boston's Beth Israel Hospital. On the basis of these data, coronary stenting was estimated to result in a higher quality-adjusted life expectancy than conventional angioplasty but to incur additional costs as well. Compared with conventional angioplasty, stenting had an estimated incremental cost-effectiveness ratio of $23,600 per quality-adjusted life year gained. Although the cost-effectiveness ratio for stenting changed with variations in assumptions about the relative costs and restenosis rates, it remained less than $40,000 per quality-adjusted year of life gained--and thus was similar to many other accepted medical treatments--unless the stent angiographic restenosis rate was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, < 30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets.     

Psychological and social predictors of motorcycle use by young adult males in New Zealand

Motorcycle riding is a significant cause of serious injuries to young males. Little is known about the psychological and social characteristics of these riders, despite such knowledge being potentially important for the targeting of appropriate injury prevention interventions. Using problem-behaviour theory to broadly guide and structure the research, the present study focused on identifying predictors of motorcycle riding. Previous research investigating differences between riders and non-riders has tended to be inconclusive, methodologically limited, and lacking in explicit theoretical foundations. The present research was based on the birth cohort enrolled in the Dunedin Multidisciplinary Health and Development Study (DMHDS), a comprehensive New Zealand longitudinal study of health, development, attitudes, and behaviours. Logistic regression models were built using prior measures of health risk behaviour, other psychological and social factors, and motorcycle riding history as potential predictors of any motorcycle use at the age of 18 years. The strongest predictors were early motorcycle riding, including illegal on-road driving at age 13 (OR 4.0; 95% CI 1.7, 9.1), below average reading skills (OR 2.4; 95% CI 1.3, 4.6) and fighting in a public place at age 15 (OR 2.9; 95% CI 1.2, 6.9). It was of particular interest that this profile tended to fit less well those subgroups of riders with greatest exposure to on-road motorcycle driving. Although based on small numbers, this finding was consistent with earlier cross-sectional research that linked casual and unlicensed driving with less protective motorcycling opinions and behaviours. Some implications for injury prevention and public policies regarding motorcycling are discussed. In particular, stricter enforcement of present licensing regulations and stronger penalties for their violation could help to reduce the number of less responsible riders.     

The New Zealand Rugby Injury and Performance Project: I. Design and methodology of a prospective follow-up study

Injury resulting from participation in sporting and physical recreational activities is a major contributor to the overall incidence of injury in the developed world. If sports injuries are to be reduced, a comprehensive approach must be taken to define the nature and magnitude of the problem, to establish models of relationships between risk factors, protective factors and injury experience, and to address injury through well designed intervention and evaluation programmes. The Rugby Injury and Performance Project (RIPP) is a prospective cohort study designed to examine the risk and protective factors for rugby injury. Data were collected on potential risk and protective factors from the RIPP cohort pre-season. Data on exposure to rugby, injury events and medical treatments were collected from the players each week during the season through telephone interviews. Pre-season measures were repeated post-season. A key feature of the design was that data were collected on both injured and non-injured players, allowing a longitudinal comparison of the injury experience of players with and without the factors of interest. A wealth of information was collected on each cohort member during the pre-season interview. A contact rate of 90% was achieved during the weekly follow-up phase. Post-season questionnaires were completed by 76% of the players and 88% of the coaches. Recommendations are made for the use of this methodology by other researchers and future directions for RIPP are described.     

The practice of obstetrics in Mongolia

Sponsored by the US Department of State and the US Army Pacific as part of a Medical Readiness Training Exercise, 17 physicians from Tripler Army Medical Center traveled to Outer Mongolia during September 1995 to examine the practice of medicine in the country. The obstetrical care observed was delivered at Third Women's Hospital in Ulanbataar. Prenatal care in Mongolia is provided mainly by family physicians, with the family doctor visiting each pregnant patient every month for the first 5 months, increasing to weekly visits at 7 months. The patient is taken to an obstetrical or women's and children's hospital when she reaches term or goes into labor. The staff at Third Women's Hospital deliver approximately 2000 babies annually and perform approximately 1000 pregnancy terminations through sharp curettage. The cesarean section rate is reported to be 10%. The hospital has no laboratory or X-ray capability, but can send out for such tests on rare occasions. During labor, patients are fully ambulatory on an as-needed basis. Fetal monitoring is not routinely available, except for occasional auscultation, patients in labor were not given IV fluid, delivery rooms were bleak and with only antiquated equipment, lighting was poor, and gloves were reused until they were too tattered for reuse. The authors discuss their experience with 3 cesarean sections and 1 ectopic pregnancy performed while in the country.     

S-adenosylmethionine generation and prevention of alcoholic fatty liver by betaine

Earlier studies by other investigators have shown that S-adenosylmethionine (SAM) has the capacity to attenuate liver injury in experimental animals. In a recent study in this laboratory, it was shown that when supplemental dietary betaine was given to control and ethanol-fed rats at the level of 0.50% (W/V), SAM levels were doubled in the livers of control animals and increased fivefold in livers of ethanol-fed rats. The increased levels of SAM in the livers of ethanol-fed animals protected the livers from fatty infiltration due to ethanol feeding. In this study, an attempt was made to determine the minimum level of dietary betaine that protects against the fatty infiltration. Levels of betaine at 0.05%, 0.10%, 0.25%, and 0.50% in semiliquid control and alcohol diets were tested in rats for 30 days. When hepatic betaine, SAM, and triglyceride levels were determined, it was demonstrated that only the dietary level of betaine at 0.50% supplied enough hepatic betaine to generate the level of SAM that was required to protect against the alcoholic steatosis resulting from the dietary ethanol. These results suggest that betaine, when given in sufficient amounts, may be a promising therapeutic agent in the treatment of liver disease.     

A locus for autosomal recessive hypodontia with associated dental anomalies maps to chromosome 16q12.1

Lumbosacral defects on 20 patients were covered with a perforator-based flap. Cutaneous perforators derived from the 9th and 10th intercostal arteries, the 4th lumbar artery, and multiple gluteal perforators that penetrate the gluteus maximus muscle were used as vascular pedicles. Minor complications occurred in five cases. Using this method, minimal morbidity of the donor site is expected because the gluteus maximus need not be sacrificed. Accordingly, perforator-based flaps are especially indicated for ambulatory patients, but for paraplegic patients as well. Even in the event of recurrence, another perforator-based or musculocutaneous flap can be elevated from the ipsilateral side because of the presence of multiple perforators in the lumbosacral and gluteal regions.     

Establishment and molecular characterization of five cell lines derived from renal and extrarenal malignant rhabdoid tumors

Malignant rhabdoid tumor (MRT) is a rare, enigmatic childhood cancer characterized by extreme aggressiveness and resistance to chemotherapy. To understand better the origin of the tumor and the mechanisms by which it develops and resists treatment, five cell lines were established from patients presenting with MRT (two renal and three extrarenal tumors). All of the cell lines display the light microscopic and ultrastructural features, as well as the variable immunohistochemical profile, characteristic of MRT. All are capable of forming tumors in nude mice. Three of the cell lines have detectable abnormalities of chromosome 22: one a t(22, 22) unbalanced translocation and two others a loss of heterozygosity of polymerase chain reaction-based microsatellite markers. Northern blot analysis showed that overexpression of the c-myc message was a consistent characteristic of the five MRTs evaluated. Although mutations of the p53 gene were not detectable by sequence analysis, all of the cell lines showed nuclear accumulation of the p53 protein by an immunocytochemical analysis in a minority of the cells. This result suggests that dysfunction in a p53-dependent apoptotic pathway might play a role in the multiple drug resistance phenotype of these tumors.