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Title:
Effect of sleep deprivation on response to immunizaton [3]
Authors:
Spiegel, Karine; Sheridan, John F.; Van Cauter, Eve
Abstract:
Eleven subjects had their bedtime restricted to 4 hours (1-5 AM) for 6 nights and then extended to 12 hours per night for 7 nights to recover from sleep loss. Between 9:00 and 10:00 on the morning following the fourth short night, they were immunized against influenza. A second group of 14 subjects served as controls and maintained their usual bedtimes prior to receiving the same vaccine under the same conditions.$\backslash$n$\backslash$nResults: Ten days after vaccination, mean (SD) antibody titers in subjects who were immunized in a state of sleep debt were less than half those measured in the subjects with normal sleep times (0.50106 [0.46106] vs 1.15106 [1.00106], respectively; P=.03 by Mann-Whitney tes, see Figure. At 3 to 4 weeks after vaccination, antibody titers were no longer significantly different.$\backslash$n$\backslash$nSleep deprivation at the time of vaccination reduced the response during the log phase of antibody production despite a prolonged period of sleep recovery after vaccination.$\backslash$nBecause adults who show poorer responses to vaccines and other antigenic challenges also experience higher rates of clinical illness [ ref: McGlone and Aerden, 1987], our findings support the concept that adequate amounts of sleep are needed for optimal resistance to infectious challenge.$\backslash$n$\backslash$nImmune response$\backslash$n
Published:
2002
Title:
Effect of vegetarian diet on homocysteine levels
Authors:
Bissoli, L.; Di Francesco, V.; Ballarin, A.; Mandragona, R.; Trespidi, R.; Brocco, G.; Caruso, B.; Bosello, O.; Zamboni, M.
Abstract:
OBJECTIVE: To compare fasting total plasma homocysteine (tHcy) levels in vegans, lacto-ovovegetarians and control subjects, and to evaluate the relationships between tHcy levels and nutritional variables in vegetarians. METHODS: The study was conducted on 45 vegetarian subjects: 31 vegans (19 males, 12 females, mean age 45.8 +/- 15.8 years); 14 lacto-ovovegetarians (6 males, 8 females, mean age 48.5 +/- 14.5 years), and 29 control subjects (19 males, 10 females, mean age 43.4 +/- 16.7 years). tHcy was evaluated by high-performance liquid chromatography. Serum vitamin B(12) and folate were analyzed by automated chemiluminescence systems. Clinical records, nutritional and anthropometric variables were collected for all vegetarian subjects. RESULTS: tHcy was significantly higher in vegetarian subjects than in controls (23.9 +/- 21.3 vs. 11.6 +/- 4.9 micromol/l, p < 0.001). The prevalence of hyperhomocysteinemia was higher in vegetarians than in controls (53.3 vs. 10.3%, p < 0.001). Serum vitamin B(12) levels were lower in vegetarians than in control subjects (171.2 +/- 73.6 vs. 265.0 +/- 52.2 pmol/l, p < 0.01; normal range 220-740 pmol/l). In vegetarian subjects, significant inverse correlations were found between tHcy and serum vitamin B(12) levels (r = -0.776, p < 0.001) and between tHcy and serum folate levels (r = -0.340, p < 0.05). Positive correlations were found between tHcy and mean red cell volume (r = 0.44, p < 0.01) and between tHcy and fat-free mass (r = 0.36, p
Published:
2002
Title:
Food Politics: How the Food Industry Influences Nutrition and Health
Authors:
Nestle, Marion
Abstract:
Published:
2002
Title:
Garden-Enhanced Nutrition Curriculum Improves Fourth-Grade School Children's Knowledge of Nutrition and Preferences for Some Vegetables
Authors:
Morris, Jennifer L.; Zidenberg-Cherr, Sheri
Abstract:
Published:
2002
Title:
Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder
Authors:
Greenhill, L.; Beyer, D. H.; Finkleson, J.; Shaffer, D.; Biederman, J.; Conners, C. K.; Gillberg, C.; Huss, M.; Jensen, P.; Kennedy, J. L.; Klein, R.; Rapoport, J.; Sagvolden, T.; Spencer, T.; Swanson, J. M.; Volkow, N.
Abstract:
OBJECTIVE: To review published algorithms for guiding the use of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHODS: A consensus roundtable of 12 experts was convened to review the evidence for the safety and efficacy of MPH in the treatment of ADHD, as well as the published algorithms and practice guidelines for using MPH. The experts reviewed the algorithms for practicality and acceptability by clinicians. RESULTS: Algorithms that included MPH commonly selected it as the initial medication to be employed in the treatment of children with ADHD. Factors involved included its high efficacy, good safety record, and the ubiquitous nature of its appearance in the ADHD treatment literature. CONCLUSIONS: MPH should be considered as the first medication to be used in a treatment algorithm for children and adolescents with ADHD.
Published:
2002
Title:
Impact of tofu or tofu + orange juice on hematological indices of lacto-ovo vegetarian females
Authors:
Kandiah, Jay
Abstract:
The purpose of this study was to investigate iron status of premenopausal vegetarian women consuming tofu or tofu plus orange juice. Following a three day pre-period, 14 lacto-ovo vegetarians were randomly divided into two experimental periods of 30 days each. For the first 30 days, one half of the subjects (n = 7) received 6 oz (173 grams) of tofu/day (T) while the other half of the subjects (n = 7) received 6 oz of tofu/day along with 303 mg of vitamin C/d (TO). After 30 days, there was a crossover of the diets. Iron status was assessed by measuring serum ferritin and hemoglobin concentrations on the first day of the study and at the end of each experimental period. The Mann Whitney-U test was significant during the first (W = 17.5; Z = -2.095; p = 0.0361) and over the second (W = 40.0; Z = -2.611; p = 0.009) experimental periods which indicated the change in hemoglobin levels for the T and TO groups were different. Mean ranks showed a greater increase in hemoglobin levels for the TO group. There was no significant difference in the change in serum ferritin levels between the T and TO groups over the first and second experimental periods. In conclusion, bioavailability of iron from tofu is enhanced by supplementation with ascorbic acid.
Published:
2002
Title:
Inflammatory atherosclerosis characteristics of the injurious agent
Authors:
Frink, Richard J
Abstract:
Published:
2002
Title:
Inhibitors and Breakers of Advanced Glycation Endproducts (AGEs): A Review
Authors:
Rahbar, S.; Figarola, J. L.
Abstract:
Published:
2002
Title:
Is there a link between wild meat and food security?
Authors:
Bennett, Elizabeth L.
Abstract:
Published:
2002
Title:
Physiological effects of medium-chain triglycerides: potential agents in the prevention of obesity.
Authors:
St-Onge, Marie-Pierre; Jones, Peter J H
Abstract:
Medium chain fatty acids (MCFA) are readily oxidized in the liver. Animal and human studies have shown that the fast rate of oxidation of MCFA leads to greater energy expenditure (EE). Most animal studies have also demonstrated that the greater EE with MCFA relative to long-chain fatty acids (LCFA) results in less body weight gain and decreased size of fat depots after several months of consumption. Furthermore, both animal and human trials suggest a greater satiating effect of medium-chain triglycerides (MCT) compared with long-chain triglycerides (LCT). The aim of this review is to evaluate existing data describing the effects of MCT on EE and satiety and determine their potential efficacy as agents in the treatment of human obesity. Animal studies are summarized and human trials more systematically evaluated because the primary focus of this article is to examine the effects of MCT on human energy metabolism and satiety. Hormones including cholescytokinin, peptide YY, gastric inhibitory peptide, neurotensin and pancreatic polypeptide have been proposed to be involved in the mechanism by which MCT may induce satiety; however, the exact mechanisms have not been established. From the literature reviewed, we conclude that MCT increase energy expenditure, may result in faster satiety and facilitate weight control when included in the diet as a replacement for fats containing LCT.
Published:
2002
Title:
Proteins Are Degraded to Amino Acids
Authors:
Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert
Abstract:
Dietary protein is a vital source of amino acids. Proteins ingested in the diet are digested into amino acids or small peptides that can be absorbed by the intestine and transported in the blood. Another source of amino acids is the degradation of defective or unneeded cellular proteins.
Published:
2002
Title:
Repeated sauna treatment improves vascular endothelial and cardiac function in patients with chronic heart failure
Authors:
Kihara, Takashi; Biro, Sadatoshi; Imamura, Masakazu; Yoshifuku, Shiro; Takasaki, Kunitsugu; Ikeda, Yoshiyuki; Otuji, Yutaka; Minagoe, Shinichi; Toyama, Yoshifumi; Tei, Chuwa
Abstract:
OBJECTIVES: The purpose of this study was to determine the mechanism by which 60°C sauna treatment improves cardiac function in patients with chronic heart failure (CHF). BACKGROUND: We have previously reported that repeated 60°C sauna treatment improves hemodynamic data and clinical symptoms in patients with CHF. We hypothesized that the sauna restores endothelial function and then improves cardiac function. METHODS: Twenty patients (62 ± 15 years) in New York Heart Association (NYHA) functional class II or III CHF were treated in a dry sauna at 60°C for 15 min and then kept on bed rest with a blanket for 30 min, daily for two weeks. Ten patients with CHF, matched for age, gender and NYHA functional class, were placed on a bed in a temperature-controlled (24°C) room for 45 min as the nontreated group. Using high-resolution ultrasound, we measured the diameter of the brachial artery at rest and during reactive hyperemia (percent flow-mediated dilation, %FMD: endothelium-dependent dilation), as well as after sublingual administration of nitroglycerin (%NTG: endothelium-independent dilation). Cardiac function was evaluated by measuring the concentrations of plasma brain natriuretic peptide (BNP). RESULTS: Clinical symptoms were improved in 17 of 20 patients after two weeks of sauna therapy. The %FMD after two-week sauna treatment significantly increased from the baseline value, whereas the %NTG-induced dilation did not. Concentrations of BNP after the two-week sauna treatment decreased significantly. In addition, there was a significant correlation between the change in %FMD and the percent improvement in BNP concentrations in the sauna-treated group. In contrast, none of the variables changed at the two-week interval in the nontreated group. CONCLUSIONS: Repeated sauna treatment improves vascular endothelial function, resulting in an improvement in cardiac function and clinical symptoms. © 2002 by the American College of Cardiology Foundation.
Published:
2002
Title:
Social problems associated with ADHD vs. ODD in children referred for friendship problems
Authors:
Frankel, Fred; Feinberg, David
Abstract:
Four groups were composed of children referred for friendship problems (age range: 6 to 12 years old). One group was diagnosed with both Attention Deficit Hyperactivity Disorder (ADHD) and Oppositional-Defiant Disorder (ODD), one group with ADHD only, one group with ODD only and one group with neither disorder. Parents and teachers were given questionnaires to rate the social behavior of each child. The groups differed significantly on one parent scale (Self-control) and one teacher scale (Aggression). Inspection of the items composing these scales suggested that some items measured social relationships with adults while other items measured peer relationships. Subsequent factor analysis separated peer and adult components. Analysis of subscales derived from factor analysis revealed the diagnosis of ADHD was associated with increases in classroom disruption and decreased resistance to provocation by peers, while the diagnosis of ODD was associated with increased in hostility towards peers, decreased resistance to provocation by peers and decreased respect for adults. Limitations of the study were: domains of social functioning assessed, sample size and diversity, and the absence of a comparison group with adequate peer relationships. Social skills programs should target social deficits associated with ODD and ADHD. The scales refined in the present study offer a convenient means of assessing peer dysfunction from the points of view of parents and teachers.
Published:
2002
Title:
The McKeown Thesis: A Historical Controversy and Its Enduring Influence
Authors:
Colgrove, James
Abstract:
The historical analyses of Thomas McKeown attributed the modern rise in the world population from the 1700s to the present to broad economic and social changes rather than to targeted public health or medical interventions. His work generated considerable controversy in the 1970s and 1980s, and it continues to stimulate support, criticism, and commentary to the present day, in spite of his conclusions’ having been largely discredited by subsequent research. The ongoing resonance of his work is due primarily to the importance of the question that underlay it: Are public health ends better served by targeted interventions or by broad-based efforts to redistribute the social, political, and economic resources that determine the health of populations?
Published:
2002
Title:
The backbone of history: health and nutrition in the Western Hemisphere
Authors:
Abstract:
"The Backbone of History defines the emerging field of macrobioarchaeology by gathering, skeletal evidence on seven basic indicators of health to assess chronic conditions that affected individuals who lived in the Western Hemisphere from 5000 B.C. to the late nineteenth century. Signs of biological stress in childhood and of degeneration in joints and in teeth increased in the several millennia before the arrival of Columbus as populations moved into less healthy ecological environments. Thus, pre-Colombian Native Americans were among the healthiest and the least healthy groups to live in the Western Hemisphere before the twentieth century."--Jacket.
Published:
2002
Title:
The birth of a Catholic Inuit community. The transition to Christianity in Pelly Bay, Nunavut, 1935-1950
Authors:
Remie, Cornelius; Oosten, Jarich
Abstract:
The transition to Catholicism in Pelly Bay is usually described as a successful conquest of a pagan terra nullius, a process in which Inuit played only a passive role. In fact, there was already a nucleus of Catholics in Pelly Bay when the first missionary arrived. Inuit invited him to come and stay with them. This article describes the early years of the transition to Catholicism, as well as some religious, political and economic factors that played a part in this process. Missionary sources reveal that Inuit were by no means passive consumers, but active participants with their own interests and agendas. The missionaries appear to have been more concerned with the containment of the westward expansion of Anglicanism than the survival of paganism. Although the missionaries assumed leadership roles in many fields, they were often not aware of the extent to which Inuit continued traditional practices outside the scope of the missionaries. Moreover, many traditional practices were integrated into Christianity. Within the context of the Catholic Church, Inuit developed their own form of religiosity responding to their existential and cultural needs.
Published:
2002
Title:
Therianthropes in San Rock Art
Authors:
Jolly, Pieter
Abstract:
San paintings of therianthropes, beings that combine human and non-human features, are described and analysed in order to formulate a theory concerning the meaning of these paintings for the people who made and viewed them. The range of therianthrope paintings is described. Four explanations, or theories, concerning the therianthropes are discussed and evaluated in relation to San religious rites and beliefs and the physical forms taken by therianthropes in the art. These explanations or theories focus respectively on animal-masked/costumed shamans, shamans transformed into animals or other creatures while in altered states, the spirits of dead shamans and the human-animal beings of San myths. Physical as well as deeper, structural, conceptual correspondences between these classes of beings in San religious thought indicate that they are all related and relevant to the way in which we should interpret the therianthropes.
Published:
2002
Title:
Translocation and Enhanced Fatty Acid Uptake in Adipocytes
Authors:
Stahl, Andreas; Evans, James G; Pattel, Shraddha; Hirsch, David; Lodish, Harvey F
Abstract:
Published:
2002
Title:
[Estimation of action of lactoovovegetarian and vegan diets on blood level of atherogenic lipoproteins in healthy people]
Authors:
Medkova, I. L.; Mosiakina, L. I.; Biriukova, L. S.
Abstract:
The biochemical status of 72 vegetarians (aged 40-60) was studied; 35 persons kept to a lactoovovegetarian diet and 37 persons followed a vegan diet (vegetable food only). As the results of the investigation showed, almost all of the biochemical parameters of blood tests in the both groups were kept to the physiological norm. A pronounced hypolipidemic effect of both the diets was observed (the total cholesterol level was 5.24 +/- 0.28 mmol/l in the vegetarian group and 3.26 +/- 0.17 mmol/l in the vegan group), some parameters of lipid metabolism in the group of vegan being lower then in the vegetarian group. Thus, the total cholesterol level in the vegan group was lower by 38.7%, the atherogenic coefficient--by 13.8%, the low density cholesterol--by 34.3%, triglicerides--by 28.3%. Although the above mentioned parameters of the vegan group seem to be more satisfactory than those of the vegetarian group, we could not recommend the vegan diet for long periods of time because of deficiency of some nutrients in it.
Published:
2002
Title:
[Vegetarian diet in treating elderly patients with ischemic heart disease (clinico-hemodynamic, biochemical, and hemorheological effects)]
Authors:
Ivanov, A. N.; Medkova, I. L.; Mosiagina, L. I.
Abstract:
The inclusion of balanced antiatherogenis of vegetarian diet in a complex of therapeutical means of the patients of ischemic heart disease in elderly age (average age 72.3 years) promotes normalization of clinical and biochemical parameters, correction of lipid metabolism and parameters plasma hemostasis. Vegetarian antiatherogenis the diet is perspective means in treatment of the patients ischemic heart disease of elderly age.
Published:
2002
Title:
[Vegetarian diets of breastfeeding women in the light of dietary recommendations]
Authors:
Strucińska, Małgorzata
Abstract:
The literature review concerning selected nutritional and health aspects of applying different vegetarian diets by breastfeeding women was presented. The only two types of vegetarian diets: lactoovo- and semi-vegetarian, when properly composed, seem to be relatively safe for mother and her child. The most threatening vegetarian diets for lactating women are those including exclusively products of plant origin (so called restricted diets: vegan or macrobiotic). The results of studies performed on mothers consuming these vegetarian diets showed deficiencies in: vitamin B12 and vitamin D (in mothers and their infants) and calcium (only in lactating women). The low intake of docosahexaenoic acid (DHA) was also characteristic in this group. Additionally the endogenous metabolism of DHA is inhibited due to high proportion of linoleic vs. linolenic acid intake. It considered that lactating women on vegetarian diet should have a greater nutritional knowledge in order to avoid deficiencies which would adversely affect mother's and her child's health.
Published:
2002
Title:
Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus
Authors:
Tanasescu, M.; Hu, F. B.; Willett, W. C.; Stampfer, M. J.; Rimm, E. B.
Abstract:
OBJECTIVES: The goal of this study was to examine the relationship between alcohol intake and risk of coronary heart disease (CHD) among men with type 2 diabetes. BACKGROUND: Type 2 diabetes is associated with an increased risk of CHD. Emerging evidence suggests that moderate alcohol intake is associated with an important reduction in risk of CHD in individuals with type 2 diabetes. METHODS: We studied 2,419 men who reported a diagnosis of diabetes at age 30 or older in the Health Professionals' Follow-up study (HPFS). During 11,411 person-years of follow-up after diagnosis, we documented 150 new cases of CHD (81 nonfatal myocardial infarction [MI] and 69 fatal CHD). Relative risks (RR) were estimated from pooled logistic regression adjusting for potential confounders. RESULTS: Alcohol use was inversely associated with risk of CHD in men with type 2 diabetes. The age-adjusted RRs corresponding to intakes of 2 drinks/day were 0.76 (95% confidence interval: [CI]: 0.52 to 1.12), 0.64 (95% CI: 0.40 to 1.02) and 0.59 (95% CI: 0.32 to 1.09), respectively, as compared with nondrinkers (p for trend = 0.06). When we controlled for body mass index, smoking, family history of MI, hypertension, hypercholesterolemia, duration of diabetes, physical activity level, vitamin E supplements and intake of trans fat, polyunsaturated fat, fiber and folate, RRs were 0.78 (95% CI: 0.52 to 1.15), 0.62 (95% CI: 0.40 to 1.00) and 0.48 (95% CI: 0.25 to 0.94) (p for trend = 0.03). The benefits of moderate consumption did not statistically differ by beverage type. CONCLUSIONS: Moderate alcohol consumption is associated with lower risk of CHD in men with type 2 diabetes.
Published:
2001-12
Title:
Apparent copper absorption from a vegetarian diet
Authors:
Hunt, J. R.; Vanderpool, R. A.
Abstract:
BACKGROUND: Vegetarian diets often contain more copper than do nonvegetarian diets, but observations of decreased plasma copper associated with vegetarian diets suggest that these diets have lower copper bioavailability than do nonvegetarian diets. OBJECTIVE: Our objective was to determine apparent copper absorption from controlled lactoovovegetarian and nonvegetarian diets. DESIGN: Eighteen women aged 20-43 y consumed lactoovovegetarian and nonvegetarian weighed diets for 8 wk each in a randomized, crossover design. The lactoovovegetarian and nonvegetarian diets provided 1.45 and 0.94 mg Cu, 38 and 16 g dietary fiber, and 1584 and 518 mg phytic acid, respectively, per 9.2 MJ (2200 kcal). After the women had been consuming each diet for 4 wk, their apparent copper absorption was determined by measuring the fecal excretion of the 65Cu stable isotope, extrinsically added to the entire menu as 65CuCl2. RESULTS: Plasma copper and ceruloplasmin were not affected by diet. The efficiency of apparent copper absorption from the lactoovovegetarian diet was less (33%) than that from the nonvegetarian diet (42%) (pooled SD: 9%; P < 0.05). However, because the lactoovovegetarian diet contained approximately 50% more copper, the total apparent copper absorption from the lactoovovegetarian diet (0.48 mg/d) was greater than that from the nonvegetarian diet (0.40 mg/d) (pooled SD: 0.09 mg; P
Published:
2001-12
Title:
Can diet in conjunction with stress reduction affect the rate of increase in prostate specific antigen after biochemical recurrence of prostate cancer?
Authors:
Saxe, G. A.; Hébert, J. R.; Carmody, J. F.; Kabat-Zinn, J.; Rosenzweig, P. H.; Jarzobski, D.; Reed, G. W.; Blute, R. D.
Abstract:
PURPOSE: Epidemiological and laboratory evidence indicates that a Western diet is associated with an increased incidence of prostate cancer. Specific components of the diet, such as high saturated fat, low fiber and high meat content, may have greatest clinical significance in the later stages of tumor promotion and progression. However, departure from the conventional diet is difficult to initiate and maintain. Therefore, we combined the well-known Mindfulness-Based Stress Reduction (MBSR) program with a low saturated fat, high-fiber, plant-based diet to determine the effect on the rate of change in prostate specific antigen (PSA) in patients with biochemical recurrence after prostatectomy. MATERIALS AND METHODS: We enrolled 10 men and their partners in a 4-month group-based diet and MBSR intervention. A pre-study post-study design in which each subject served as his own control was used to compare the rate of increase in and doubling time of PSA before and after intervention. RESULTS: The rate of PSA increase decreased in 8 of 10 men, while 3 had a decrease in absolute PSA. Results of the signed rank test indicated a significant decrease in the rate of increase in the intervention period (p = 0.01). Estimated median doubling time increased from 6.5 months (95% confidence interval 3.7 to 10.1) before to 17.7 months (95% confidence interval 7.8 to infinity) after the intervention. CONCLUSIONS: Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer. Larger-scale randomized studies are warranted to explore further the preventive and therapeutic potential of diet and lifestyle modification in men with prostate cancer.
Published:
2001-12
Title:
Characteristics of vegetarian adolescents in a multiethnic urban population
Authors:
Perry, C. L.; Mcguire, M. T.; Neumark-Sztainer, D.; Story, M.
Abstract:
PURPOSE: To examine the prevalence of adolescents' vegetarianism in a multiethnic, urban population, and its correlates with demographic, personal, weight-related, and behavioral factors. METHODS: Self-report and anthropometric data were collected from a representative sample of 4746 adolescents from 31 public middle schools and high schools in the Twin Cities area of Minnesota. Students answered questions concerning vegetarianism, food and weight, and health behaviors. Height and weight were directly measured. Comparisons were made between self-reported vegetarians and nonvegetarians; these analyses also assessed gender and race/ethnicity interactions. In the second set of analyses, demographic and behavioral characteristics of more restricted and semi-vegetarians were examined. Analyses were done by logistic regression. RESULTS: Teenage vegetarians comprise about 6% of the sample. The vegetarians were more likely than nonvegetarians to be female, not black, weight- and body-conscious, dissatisfied with their bodies, and involved in a variety of healthy and unhealthy weight control behaviors. Vegetarians more often reported having been told by a physician that they had an eating disorder and were more likely to have contemplated and attempted suicide. Vegetarian males were found to be an especially high risk group for unhealthy weight control practices. Few ethnic group differences among vegetarians were noted. Adolescents who did not eat chicken and fish were at lower risk than those who also ate chicken and fish. CONCLUSIONS: Adolescent vegetarians are at greater risk than others for involvement in unhealthy and extreme weight control behaviors. Vegetarian males are at particularly high risk. Vegetarianism among adolescents may therefore be a signal for preventive intervention. Adolescents who choose to become vegetarians may also need to learn how to healthfully do so.
Published:
2001-12
Title:
TRAIL/Apo-2L: mechanisms and clinical applications in cancer
Authors:
Srivastava, R. K.
Abstract:
TNF-related apoptosis-inducing ligand (TRAIL/APO-2L) is a member of the TNF family that promotes apoptosis by binding to the transmembrane receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. Its cytotoxic activity is relatively selective to the human tumor cell lines without much effect on the normal cells. Hence, it exerts an antitumor activity without causing toxicity, as apparent by studies with several xenograft models. This review discusses the intracellular mechanisms by which TRAIL induces apoptosis. The major pathway of its action proceeds through the formation of DISC and activation of caspase-8. The apoptotic processes, therefore, follow two signaling pathways, namely the mitochondrial-independent activation of caspase-3, and mitochondrial-dependent apoptosis due to cleavage of BID by caspase-8, the formation of apoptosomes, and activation of caspase-9 and the downstream caspases. Bcl-2 and Bcl-X(L) have no effect on TRAIL-induced apoptosis in lymphoid cells, whereas these genes block or delay apoptosis in nonlymphoid cancer cells. TRAIL participates in cytotoxicity mediated by activated NK cells, monocytes, and some cytotoxic T cells. Hence, TRAIL may prove to be an effective antitumor agent. In addition, it may enhance the effectiveness of treatment with chemotherapeutic drugs and irradiation. Nontagged Apo-2L/TRAIL does not cause hepatotoxicity in monkeys and chimpanzees and in normal human hepatocytes. Thus, nontagged Apo-2L/TRAIL appears to be a promising new candidate for use in the treatment of cancer.
Published:
2001-12
Title:
Effects of a high-fat diet on postabsorptive and postprandial testosterone responses to a fat-rich meal
Authors:
Volek, J. S.; Gómez, A. L.; Love, D. M.; Avery, N. G.; Sharman, M. J.; Kraemer, W. J.
Abstract:
Postprandial testosterone concentrations have been shown to significantly decrease after a fat-rich meal, which may be due to inhibition of testosterone production by chylomicrons. We examined the effects of a high-fat diet known to reduce postprandial chylomicrons on the testosterone response to a fat-rich meal. Total testosterone (TT), free testosterone (FT), cortisol, and insulin responses to a high-fat test meal containing 5.44 MJ (1,300 kcal, 11% carbohydrate, 3% protein, 86% fat) were determined before (week 0) and after (week 8) an 8-week high-fat diet (64% fat) in 11 healthy men. The high-fat diet resulted in significant reductions in postabsorptive and postprandial serum triacylglycerols (55% and 50%, respectively). There were no significant changes in postabsorptive serum TT, FT, and cortisol, but insulin concentrations were significantly (P
Published:
2001-11
Title:
Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum
Authors:
Mori, M.; Itabe, H.; Higashi, Y.; Fujimoto, Y.; Shiomi, M.; Yoshizumi, M.; Ouchi, Y.; Takano, T.
Abstract:
A monoclonal antibody, ASH1a/256C (256C), which binds to atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbit (WHHL) aorta in vivo, recognizes complex structures of phosphatidylcholine mixed with neutral lipids. In the present study, a cell culture system is described in which foam cells express 256C-positive lipid droplets. J774.1 macrophages were incubated in the presence of a small volume of WHHL serum for 24 h to produce foam cells, which were then incubated without the WHHL serum for 3 days. Oil red O-positive lipid droplets appeared on day 1, and were present in the cells during the whole incubation period. The lipid droplets in the cells were positively immunostained with antibody 256C on day 4, although they were negative on day 1. Expression of the antigenic lipid droplets was also induced by the addition of acetylated LDL or sera from patients with hyperlipidemia. When foam cells were induced by the addition of WHHL serum, cellular content of cholesteryl ester was greatly increased but then decreased to near basal levels by day 4. Concomitantly, cellular free cholesterol increased during the culture period, indicating that the cholesteryl ester changes to free cholesterol by day 4. The lipid droplets in the foam cells on day 4 were positively stained with filipin, a fluorescent probe for free cholesterol, as well as with 256C antibody, indicating that free cholesterol is enriched in antigenic lipid droplets. These observations suggest that hydrolysis and rearrangement of cellular cholesterol take place in foam cells to form complex structures of phosphatidylcholine and free cholesterol in lipid droplets.
Published:
2001-11
Title:
Is increased D2 receptor availability associated with response to stimulant medication in ADHD
Authors:
Ilgin, N.; Senol, S.; Gucuyener, K.; Gokcora, N.; Sener, S.
Abstract:
The purpose of this study was to estimate striatal dopamine (D2) receptor availability in non-drug treated children with attention-deficit-hyperactivity disorder (ADHD) before and after methylphenidate therapy, and to examine correlations between severity of symptoms and response rates to stimulant medication with levels of striatal D2 receptor binding. Nine children (six males, three females; mean age 9.8 years, SD 2.3 years) with ADHD participated. All underwent iodobenzamide (123I IBZM) brain SPECT within 2 hours following intravenous injection of 123I IBZM before and 3 months after methylphenidate therapy. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. Specific binding ratios at baseline were higher than the previously reported specific binding values obtained in studies using young healthy adults. D2 availability reduced significantly (paired t-test,p
Published:
2001-11
Title:
Validity of self-reported energy intake in lean and obese young women, using two nutrient databases, compared with total energy expenditure assessed by doubly labeled water
Authors:
Weber, J. L.; Reid, P. M.; Greaves, K. A.; DeLany, J. P.; Stanford, V. A.; Going, S. B.; Howell, W. H.; Houtkooper, L. B.
Abstract:
OBJECTIVE: To compare self-reported total energy intake (TEI) estimated using two databases with total energy expenditure (TEE) measured by doubly labeled water in physically active lean and sedentary obese young women, and to compare reporting accuracy between the two subject groups. DESIGN: A cross-sectional study in which dietary intakes of women trained in diet-recording procedures were analyzed using the Minnesota Nutrition Data System (NDS; versions 2.4/6A/21, 2.6/6A/23 and 2.6/8.A/23) and Nutritionist III (N3; version 7.0) software. Reporting accuracy was determined by comparison of average TEI assessed by an 8 day estimated diet record with average TEE for the same period. RESULTS: Reported TEI differed from TEE for both groups irrespective of nutrient database (P<0.01). Measured TEE was 11.10+/-2.54 and 11.96+/-1.21 MJ for lean and obese subjects, respectively. Reported TEI, using either database, did not differ between groups. For lean women, TEI calculated by NDS was 7.66+/-1.73 MJ and by N3 was 8.44+/-1.59 MJ. Corresponding TEI for obese women were 7.46+/-2.17 MJ from NDS and 7.34+/-2.27 MJ from N3. Lean women under-reported by 23% (N3) and 30% (NDS), and obese women under-reported by 39% (N3) and 38% (NDS). Regardless of database, lean women reported higher carbohydrate intakes, and obese women reported higher total fat and individual fatty acid intakes. Higher energy intakes from mono- and polyunsaturated fatty acids were estimated by NDS than by N3 in both groups of women (P
Published:
2001-11
Title:
Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocytes
Authors:
Tanaka, T.; Kouda, K.; Kotani, M.; Takeuchi, A.; Tabei, T.; Masamoto, Y.; Nakamura, H.; Takigawa, M.; Suemura, M.; Takeuchi, H.; Kouda, M.
Abstract:
Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.
Published:
2001-11
Title:
A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens
Authors:
Hafström, I.; Ringertz, B.; Spångberg, A.; von Zweigbergk, L.; Brannemark, S.; Nylander, I.; Rönnelid, J.; Laasonen, L.; Klareskog, L.
Abstract:
OBJECTIVE: Whether food intake can modify the course of rheumatoid arthritis (RA) is an issue of continued scientific and public interest. However, data from controlled clinical trials are sparse. We thus decided to study the clinical effects of a vegan diet free of gluten in RA and to quantify the levels of antibodies to key food antigens not present in the vegan diet. METHODS: Sixty-six patients with active RA were randomized to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 yr. All patients were instructed and followed-up in the same manner. They were analysed at baseline and after 3, 6 and 12 months, according to the response criteria of the American College of Rheumatology (ACR). Furthermore, levels of antibodies against gliadin and beta-lactoglobulin were assessed and radiographs of the hands and feet were performed. RESULTS: Twenty-two patients in the vegan group and 25 patients in the non-vegan diet group completed 9 months or more on the diet regimens. Of these diet completers, 40.5% (nine patients) in the vegan group fulfilled the ACR20 improvement criteria compared with 4% (one patient) in the non-vegan group. Corresponding figures for the intention to treat populations were 34.3 and 3.8%, respectively. The immunoglobulin G (IgG) antibody levels against gliadin and beta-lactoglobulin decreased in the responder subgroup in the vegan diet-treated patients, but not in the other analysed groups. No retardation of radiological destruction was apparent in any of the groups. CONCLUSION: The data provide evidence that dietary modification may be of clinical benefit for certain RA patients, and that this benefit may be related to a reduction in immunoreactivity to food antigens eliminated by the change in diet.
Published:
2001-10
Title:
APC , Signal transduction and genetic instability in colorectal cancer
Authors:
Fodde, Riccardo; Smits, Ron; Clevers, Hans
Abstract:
Colorectal cancer arises through a gradual series of histological changes, each of which is accompanied by a specific genetic alteration. In general, an intestinal cell needs to comply with two essential requirements to develop into a cancer: it must acquire selective advantage to allow for the initial clonal expansion, and genetic instability to allow for multiple hits in other genes that are responsible for tumour progression and malignant transformation. Inactivation of APC — the gene responsible for most cases of colorectal cancer — might fulfil both requirements.
Published:
2001-10
Title:
Dietary fats and diabetes mellitus: is there a good fat?
Authors:
Segal-Isaacson, C. J.; Carello, E.; Wylie-Rosett, J.
Abstract:
As knowledge of the fatty acid functions has increased, so has the complexity of making dietary fat recommendations to people with type 2 diabetes. Oleic acid seems to offer a slight advantage over linoleic acid in reducing plasma glucose, insulin levels, total cholesterol, low-density lipoproteins (LDLs), and triglycerides, but may also have atherogenic properties through another mechanism. A diet containing a higher proportion of polyunsaturated fatty acids (PUFAs) may require a concomitant increase in antioxidant intake because PUFAs oxidize easily and are then converted to oxidized LDL, which is more atherogenic. In addition to raising total and LDL cholesterol, long chain saturated free fatty acids may interact with plasma glucose to increase insulin secretion. Omega-3 fatty acids decrease triglycerides and reduce the risk of fatal cardiac arrhythmias. Glycemic control does not appear to be adversely affected by omega-3 fatty acids at amounts of up to 3 g/d.
Published:
2001-10
Title:
Effect of a lacto-ovo vegetarian diet on fasting small intestinal motility
Authors:
Andrews, J. M.; Doran, S. M.; Di Matteo, A. C.; Leong, L.; Macintosh, C.; Chiu, C. J.; Read, N. W.; Fraser, R. J.
Abstract:
BACKGROUND: Changes in diet can alter gastric and small intestinal (SI) motility. The effects of a vegetarian diet on fasting SI motility are unknown. METHODS: Manometric studies were performed in 9 lacto-ovo vegetarians (7 women) and 9 omnivores (7 women) of similar age and body mass index. On each study day, manometry was used to assess SI motility for 5 h, or 3 complete cycles of the interdigestive motor complex (IDMC). Lacto-ovo vegetarians were studied once: omnivores were studied twice, on their usual diet, and after consuming a 14-day lacto-ovo vegetarian diet. Diet diaries were kept for 5 days prior to each manometric study. Data were analysed for dietary composition and for cycle length and duration of each phase (I, II and III) of the IDMC. RESULTS: Dietary intake did not differ between chronic vegetarians and chronic omnivores apart from a trend to higher fibre intake (29 +/- 3 versus 20 +/- 3 g/day; P = 0.058). Omnivores eating a vegetarian diet showed a trend to decreased alcohol consumption (P = 0.068), but did not increase their fibre intake (20 +/- 3 versus 21 +/- 3 g/day). Neither cycle length nor duration of each IDMC phase differed between chronic vegetarians and chronic omnivores. After 14 days of a vegetarian diet, omnivores had a reduction in cycle length (128 +/- 19 versus 86 +/- 12 min; P = 0.02), with a non-significant reduction of Phase II (99 +/- 20 versus 50 +/- 8 min: P = 0.066). CONCLUSIONS: A chronic vegetarian diet has no major effect on fasting SI motility; but acute dietary change may alter the cycle length and component phases of the IDMC.
Published:
2001-10
Title:
Iatrogenic cardiopulmonary arrest during pediatric sedation with meperidine, promethazine, and chlorpromazine:
Authors:
Brown, Eric T.; Corbett, Stephen W.; Green, Steven M.
Abstract:
From the Department of Emergency Medicine, Adventist Medical Center, Portland, Oregon (E.T. Brown), and the Department of Emergency Medicine, Loma Linda University Medical Center, Loma Linda, California (S.W. Corbett, S.M. Green). Address for reprints: Stephen W Corbett, MD, Department of Emergency Medicine, Loma Linda University Medical Center A-108, 11234 Anderson Street, Loma Linda, CA 92354; e-mail: scorbett@ahs.llumc.edu The Authors would like to thank Norman Hamada, Pharm. D., for his contributions.
Published:
2001-10
Title:
Does a vegan diet reduce risk for Parkinson's disease?
Authors:
McCarty, M. F.
Abstract:
Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa.
Published:
2001-09
Title:
Oxalate content of soybean seeds (Glycine max: Leguminosae), soyfoods, and other edible legumes
Authors:
Massey, L. K.; Palmer, R. G.; Horner, H. T.
Abstract:
Consumption of soybeans and food products made from them is increasing because of their desirable nutritional value. However, the oxalate content of seeds from 11 cultivars of soybean showed relatively high levels of total oxalate from 0.67 to 3.5 g/100 g of dry weight. Oxalate primarily was found as calcium oxalate crystals. Thirteen tested commercial soyfoods contained between 16 and 638 mg of total oxalate per serving. These values compare to those of three other legume foods, peanut butter, refried beans, and lentils, which contained 197, 193, and 100 mg of total oxalate per serving, respectively. After oxalate has been absorbed from the diet, it cannot be metabolized and is excreted by the kidney into urine, where it binds to calcium forming an insoluble salt that may precipitate to form kidney stones. The amounts of total oxalate in soybean seeds, soy foods, and other common legume foods exceed current recommendations for oxalate consumption by individuals who have a history of calcium oxalate kidney/urinary stones. This study serves as the basis to find soybean cultivars lower in oxalate, which will have lower risk for kidney stone formation after human consumption.
Published:
2001-09
Title:
Vascular dilatory functions of ovo-lactovegetarians compared with omnivores
Authors:
Cl, Lin; Tc, Fang; Mk, Gueng
Abstract:
Vegetarians have lower blood pressure and lower cardiovascular mortality. Vegetarian diets may have lower cardiovascular risks through positive influence on endothelium-dependent relaxation and related functions. The objectives of this study were to assess the differences of vascular dilatory functi …
Published:
2001-09
Title:
A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
Authors:
Cummings, D. E.; Purnell, J. Q.; Frayo, R. S.; Schmidova, K.; Wisse, B. E.; Weigle, D. S.
Abstract:
The recently discovered orexigenic peptide ghrelin is produced primarily by the stomach and circulates in blood at levels that increase during prolonged fasting in rats. When administered to rodents at supraphysiological doses, ghrelin activates hypothalamic neuropeptide Y/agouti gene-related protein neurons and increases food intake and body weight. These findings suggest that ghrelin may participate in meal initiation. As a first step to investigate this hypothesis, we sought to determine whether circulating ghrelin levels are elevated before the consumption of individual meals in humans. Ghrelin, insulin, and leptin were measured by radioimmunoassay in plasma samples drawn 38 times throughout a 24-h period in 10 healthy subjects provided meals on a fixed schedule. Plasma ghrelin levels increased nearly twofold immediately before each meal and fell to trough levels within 1 h after eating, a pattern reciprocal to that of insulin. Intermeal ghrelin levels displayed a diurnal rhythm that was exactly in phase with that of leptin, with both hormones rising throughout the day to a zenith at 0100, then falling overnight to a nadir at 0900. Ghrelin levels sampled during the troughs before and after breakfast correlated strongly with 24-h integrated area under the curve values (r = 0.873 and 0.954, respectively), suggesting that these convenient, single measurements might serve as surrogates for 24-h profiles to estimate overall ghrelin levels. Circulating ghrelin also correlated positively with age (r = 0.701). The clear preprandial rise and postprandial fall in plasma ghrelin levels support the hypothesis that ghrelin plays a physiological role in meal initiation in humans.
Published:
2001-08
Title:
Attitudes towards following meat, vegetarian and vegan diets: an examination of the role of ambivalence
Authors:
Povey, R.; Wellens, B.; Conner, M.
Abstract:
Vegetarianism within the U.K. is growing in popularity, with the current estimate of 7% of the population eating a vegetarian diet. This study examined differences between the attitudes and beliefs of four dietary groups (meat eaters, meat avoiders, vegetarians and vegans) and the extent to which attitudes influenced intentions to follow each diet. In addition, the role of attitudinal ambivalence as a moderator variable was examined. Completed questionnaires were obtained from 111 respondents (25 meat eaters, 26 meat avoiders, 34 vegetarians, 26 vegans). In general, predictions were supported, in that respondents displayed most positive attitudes and beliefs towards their own diets, and most negative attitudes and beliefs towards the diet most different form their own. Regression analyses showed that, as predicted by the Theory of Planned Behaviour, attitudes, subjective norm and perceived behavioural control were significant predictors of intention to follow each diet (apart from the vegetarian diet, where subjective norm was non-significant). In each case, attitudinal ambivalence was found to moderate the attitude-intention relationship, such that attitudes were found to be stronger predictors at lower levels of ambivalence. The results not only highlight the extent to which such alternative diets are an interesting focus for psychological research, but also lend further support to the argument that ambivalence in an important influence on attitude strength.
Published:
2001-08
Title:
Biomonitoring the intake of garlic via urinary excretion of allyl mercapturic acid
Authors:
Verhagen, H.; Hageman, G. J.; Rauma, A. L.; Versluis-de Haan, G.; van Herwijnen, M. H.; de Groot, J.; Törrönen, R.; Mykkänen, H.
Abstract:
Allium vegetables (onions, leeks, chives) and in particular garlic have been claimed to have health-promoting potential. This study was conducted to get insight into the perspectives for monitoring the intake of garlic by a biomarker approach. Chemically, the biomarker results from exposure to gamma-glutamyl-S-allyl-l-cysteine, which is first hydrolysed by gamma-glutamine-transpeptidase resulting in the formation of S-allyl-l-cysteine. The latter compound is subsequently N-acetylated by N-acetyltransferase into S-allyl-mercapturic acid (ALMA) and excreted into urine. The mercapturic acid was measured in urine using gaschromatography with mass spectrometry. Thus the intake of garlic was determined to check the compliance of garlic intake in a placebo-controlled intervention study. Results indicate that S-allyl-mercapturic acid could be detected in 15 out of 16 urine samples of garlic supplement takers, indicating good compliance. In addition, the intake of garlic was also monitored in a cross-section study of vegans versus controls in Finland, in which no differences in garlic consumption nor in ALMA output were recorded between vegans and controls. These data indicate good possibilities for further studies in the field of biomarkers to investigate the putative chemopreventive effects of garlic and garlic-containing products.
Published:
2001-08
Title:
Low-protein diet suppresses serum insulin-like growth factor-1 and decelerates the progression of growth hormone-induced glomerulosclerosis
Authors:
Doi, S. Q.; Rasaiah, S.; Tack, I.; Mysore, J.; Kopchick, J. J.; Moore, J.; Hirszel, P.; Striker, L. J.; Striker, G. E.
Abstract:
A low-protein (LP) diet has been associated with amelioration of renal function in glomerulosclerosis (GS). However, the mechanisms involved are still unclear. We have used a mouse transgenic for bovine growth hormone (GH), which develops progressive GS and exhibits consistently elevated levels of circulating GH and insulin-like growth factor (IGF)-1, to study the effect of dietary protein restriction. LP (6% protein) and normal-protein (NP, 20% protein) diets were maintained for 30 weeks in mice with established GS of mild/moderate degree. The degree of GS was markedly attenuated in LP compared to NP mice. Quantitative analysis revealed a significantly lower GS index (1.4 +/- 0.9 in LP vs. 2.8 +/- 0.8 in NP) and glomerular volume (0.8 x 10(6) +/- 0.1 x 10(6) microm(3) in LP vs. 1.2 x 10(6) +/- 0.1 x 10(6) microm(3) in NP) in mice with restricted protein intake. These morphologic changes were accompanied by a significant reduction in renal expression of alpha(1) type-IV collagen (2.4-fold) and tenascin (1.4-fold) in LP mice. Serum IGF-1 decreased by 40% and showed a significant correlation with alpha(1) type-IV collagen expression with the LP diet. The present finding supports the use of the LP diet to decelerate the progression of GS and furthermore suggests that one of the mechanisms involved in this process is the GH/IGF-1 regulation by protein intake.
Published:
2001-08
Title:
Myogenic satellite cells: Physiology to molecular biology
Authors:
Hawke, Thomas J.; Garry, Daniel J.
Abstract:
Adult skeletal muscle has a remarkable ability to regenerate following myotrauma. Because adult myofibers are terminally differentiated, the regeneration of skeletal muscle is largely dependent on a small population of resident cells termed satellite cells. Although this population of cells was identified 40 years ago, little is known regarding the molecular phenotype or regulation of the satellite cell. The use of cell culture techniques and transgenic animal models has improved our understanding of this unique cell population; however, the capacity and potential of these cells remain ill-defined. This review will highlight the origin and unique markers of the satellite cell population, the regulation by growth factors, and the response to physiological and pathological stimuli. We conclude by highlighting the potential therapeutic uses of satellite cells and identifying future research goals for the study of satellite cell biology.
Published:
2001-08
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