Proscar

Paula F. Miller, MD

• Clinical Associate Professor of Medicine
• Director, Cardiac Rehabilitation
• Director, Women? Heart Program
• Division of Cardiology
• University of North Carolina School of Medicine
• Chapel Hill, North Carolina

This study was large androgen hormone feed loop buy 5mg proscar amex, but lacked objective outcome measures androgen insensitivity syndrome hormone therapy order proscar 5mg visa, did not report dosage parameters and the intervention may have been too short dr lam prostate oncology specialists buy proscar with mastercard. The patients also used 53 pain medication prostate relief proscar 5mg on-line, but it is unsure if they were controlled for androgen nuclear hormone receptor buy 5 mg proscar with amex. The study was not blinded prostate 06 purchase proscar 5mg overnight delivery, and it was unclear if the groups were equal at baseline. It was not randomised or blinded, lacked objective outcome measures, there was no statistical analysis of the data and the intervention parameters were not reported adequately. There was significantly improved healing to their donor sites compared to 38 patients who received a placebo. One 30-minute treatment was given pre-medication to the donor site and then four times daily postoperatively, for seven days. The group sizes varied significantly, and it was unclear if they were equivalent at the baseline. The study however lacked in most methodological areas including the design, outcome measures and statistics, and hence the results could not be accepted on face value. Although this pilot trial was published several years ago, more studies on this condition have not been reported. As the review did not employ a cut-off (Downs and Black) score for the methodological quality, all the identified studies were included. However, the conclusions drawn here were influenced primarily by the results from well-designed studies besides the overall evidence from all the studies. The same cannot be stated about acute ankle injuries as the studies have shown mixed results. As identified, the ?postoperative pain? and ?postoperative wound healing? groups potentially overlapped. The allocation of studies was performed based on the main outcome as identified by their author. The key features of the studies, including dose parameters (where reported) and the Downs and Black scores are given as tables in the respective sections. Among these five studies were clinical trials,247-251 one was a cohort study194 and the other two were case studies. Nelson and colleagues251 reported that 15 participants when treated with an active 6. The benefits of this treatment beyond the immediate post treatment phase and its effects on the functional QoL are therefore unknown. Significant reduction in the pain scores at one and four weeks post treatment was reported by the active group participants compared to the placebo group. While the patients also took pain medications, they were not accounted for in the data analysis. Pain was the only outcome measured; hence its effect on functional QoL is unknown similar to the above study. Hyperthermia was induced inside the knee joints and significant pain relief was obtained. The authors used an invasive metallic thermocouple that remained in situ for the duration of treatment to record the temperature inside the joint. This was not a controlled clinical trial; hence the results needed to be interpreted with caution. However, the patient treatment protocols were variable depending on their condition. A cohort of 13 patients (15 shoulder joints) were studied, two-thirds of which reported pain relief over three months. Both studies being small case series did not provide much insight into the usefulness of such therapy. Moreover, the results of the clinical studies themselves must be weighed against their volume and overall methodological quality, several of which were seriously lacking as described above. The base frequencies used were different in virtually every study, hence no comparison was possible. Fifty-nine studies were related to conditions on pain and inflammation, 16 studies to tissue healing and the remaining seven studies to other less reported conditions such as joint stiffness. One clinical trial291 and five case studies292-296 involved various gynaecological conditions giving rise to pelvic pain. However, all these early studies were affected by significant methodological limitations such as improper randomisation, lack of appropriate statistical analysis, lack of validated outcome measures and inequivalent groups at baseline. Of this the study by Callaghan and colleagues268 was very small and statistically underpowered. The second study by Laufer and colleagues269 also had similar limitations despite being a larger trial. The study had a modest sample (36 participants in three groups) but did not use a randomised design. Moreover, the groups were not equal at the baseline in terms of pain levels, and the use of pain medication was not monitored or controlled for. Also, there was 15% drop-out of participants, which was not considered in the data analysis. The study suggested that increasing the treatment duration did not commensurately increase the rate of improvement of symptoms. This was a small pilot study with 36 participants in three groups and no follow-ups. All groups including the placebos improved their pain scores significantly and the only difference between the groups was that there was reduced paracetamol intake in the active groups at the end of the intervention, with no difference between the active groups. Self-reported pain and function improved in all three groups significantly, but the group results were not significantly different from each other. Follow-up assessments were absent in both studies and neither did they report the dose parameters. Where reported the treatment power and overall duration of intervention varied greatly, but the rationale for such a selection was not reported. The 62 number of intervention weeks varied from single to several weeks in most studies (average of 3?6 weeks). The intervention parameters reported in those studies suggest that a mean dose at or above 14. In the first study, the use of medication was not controlled, and the authors failed to report the intervention parameters. Both studies did not demonstrate sufficient equivalence between the groups at baseline. The outcome was unaffected by adding an exercise regime to the intervention or using different shortwave pulse patterns. Both studies did not demonstrate sufficient equivalence between the groups at baseline. The study by Wagstaff and colleagues288 had several additional methodological issues. Likewise, no commonalities could be drawn on dosing or any dose-related information owing to the lack of information supplied and the inconsistency where such information was supplied. This was a small study (20 participants in two groups) without any long follow-up assessments. However, this study involved 55 different therapists to deliver the intervention, potentially raising reliability concerns. The study did not recruit the anticipated number of participants (70 instead of the expected 140). Their intervention duration was significantly longer with the wearable device (over 200 sessions in 13 15 weeks, 30 minutes twice daily) although dose parameters were not reported. Chronic shoulder pain is another clinical area where studies have been identified. However, the effects were less pronounced when compared to manual therapy (Cyriax approach). Shortwave dose parameters were not reported and the duration of intervention at two weeks may potentially have been too short for a chronic condition such as the adhesive capsulitis. Both studies had significant methodological flaws including a lack of standardised objective outcome measures and poor reporting. This was not a controlled study and neither did it undertake any statistical analysis. This trial had numerous methodological limitations including absence of valid outcome measures and absence of statistical analysis. Improved methods were employed by Salzberg and colleagues313 and Kloth and colleagues314 in their studies although the sample was small in the latter. While all groups improved significantly, there were no significant differences between the groups, which implied that there was no dose-response relationship in this case. All three studies were potentially statistically underpowered and there were issues with poor baseline equivalence between their study groups. Well-designed and adequately controlled studies on tissue healing were low in number. Similar methodological limitations and dosing and reporting issues as discussed previously alongside the other groups of studies were also relevant to this segment. While the first one was a non-randomised multi-group study, the second study only featured one group with no comparator treatments. The authors suggested that proper technique and caution will enable such safe delivery of a thermal modality. The above studies only provided limited information as they were not clinical trials. Full multi-group clinical trials with appropriate methodology need to be carried out before any conclusions can be drawn. As the review did not employ a cut-off (Downs and Black) score for the methodological quality, all the identified literature was included. However, the conclusions drawn here are influenced primarily by the results from well-designed studies besides the overall evidence from the respective cohort (like the acute studies). A clear association could not be found between the quality scores obtained by the studies and their reported clinical outcome. Well designed and adequately controlled studies on tissue healing were low in number. Like most of the studies on tissue healing, all the identified studies in this area were case studies. Proper clinical trials are yet to be carried out in this area; hence no recommendations can be made. However, there is no clear indication from the experimental studies as to what may be their underpinning mechanism of action. The base frequencies used were different in virtually every study, hence no comparison was achievable. The overall quality of the studies should be considered while interpreting the evidence reported here. Reporting has been poor overall, although the trend seemed to improve in the newer studies (reporting of dose-related information continued to be a problem). In this review recommendations have been made where possible depending on the level of information available. Where participant drop-outs were high, they were not accounted for in the final analysis in most studies (no intention-to-treat analysis) as would be expected from a more recent publication. Since most of that literature was outwith the primary remit of this project, only those studies that were directly relevant to therapy-related clinical practice were included here. Several studies that were relevant to this research project but conducted on non-clinical samples/populations such as laboratory animals, tissue models (in vitro 81 studies) or asymptomatic humans (healthy-subject studies) have also been discussed briefly. The studies belonged to either a smaller ?acute conditions? (30 studies; 25%) subgroup or a larger ?chronic conditions? (90 studies; 75%) subgroup. Both groups contained studies that employed various methodological approaches ranging from case studies to multi-group clinical trials. They also contained similar application categories mainly the studies on pain and inflammation and the studies on tissue healing. A comparison and contrast of the main results of the reviews from both the acute and chronic subgroups are given in Table 3. The clinical areas of research, methodological shortcomings of the studies, and issues with reporting remained common for both acute and chronic subgroups. In both categories, a clear association could not be found between the quality scores (Downs and Black) obtained by the studies and their reported clinical outcome. Several studies considered here were affected by significant methodological issues as identified in the relevant sections, which appeared to be common to both acute and chronic categories. Yet, research in this area continues to be minimal, warranting substantially more work. The purpose of this chapter is primarily to outline all physiological measurement techniques that were relevant to the work carried out in this research project, explain the principles of measurement and report all pilot experiments that were carried out. To avoid repetition in the following chapters, reference will be made to the contents of this chapter where relevant while describing the methodology. The chapter will also describe the procedures adopted to process the resultant data. It will explain the measures relating to superficial, deep and systemic physiological responses. It was a brand-new factory calibrated machine pretested to 85 ensure reliability and accuracy of output. This medium insulates its metallic body from the skin surface, thereby forming a capacitor with the treated tissues. Energy delivery to the body is enabled using a conductive cream (coupling medium) (Figure 4. The device offers different sizes of round metallic treatment electrodes for both modes of treatment (Figure 4.

Weight loss on a low-fat diet: Consequence of the imprecision of the control of food intake in humans prostate enlarged symptoms proven 5mg proscar. Does childhood and adolescence provide a unique opportunity for exer cise to strengthen the skeleton? Exercise pre vents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet androgen hormone regulation buy 5 mg proscar overnight delivery. Diet prostate cancer test order proscar master card, prevalence and 10-year mortal ity from coronary heart disease in 871 middle-aged men prostate removal and sexual health purchase proscar master card. The inverse relation between fish consumption and 20-year mortality from coronary heart disease mens health weight loss buy 5 mg proscar with amex. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population prostate cancer yellow skin generic proscar 5mg with mastercard. Cell cycle arrest and induction of apoptosis in pancreatic cancer cells exposed to eicosapenta enoic acid in vitro. No change in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet. Nutrient intakes and body weights of persons consuming high and moderate levels of added sugars. Effect of the glycemic index and content of indigestible carbohydrates of cereal-based breakfast meals on glu cose tolerance at lunch in healthy subjects. Self-report of physical activity and pat terns of mortality in Seventh-day Adventist men. Energy and macronutrient intake in relation to cancer incidence among Swedish women. Colorectal adenomas and diet: A case-control study of subjects participating in the Nottingham Faecal Occult Blood Screening Programme. Dietary habits and incidence of noninsulin-dependent dia betes mellitus in a population study of women in Gothenburg, Sweden. Effects of physical activity, body weight and composition, and muscular strength on bone density in young women. Effects on serum lipids of different dietary fats associated with a high sucrose diet. Physical activity and incidence of non insulin-dependent diabetes mellitus in women. Long-term effects on lipid metabolism of weight reduction on lactovegetarian and mixed diet. High-fat, low-carbohydrate diet and the etiology of non-insulin-dependent diabetes mellitus: the San Luis Valley Dia betes Study. Dietary fat and insulin sensitivity in a triethnic population: the role of obesity. Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. Soy protein and casein in cholesterol enriched diets: Effects on plasma lipoproteins in normolipidemic subjects. Diet composition, energy intake, and exercise in relation to body fat in men and women. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Lipoprotein lipase activity in adipose tissue and skeletal muscle of runners: Relation to serum lipoproteins. Rela tionship of dietary saturated fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study. Carbohydrate-induced hypertriacylglycerolemia: Historical perspective and review of biological mechanisms. Nonlipoprotein risk factors for coronary heart disease: Evalua tion and management. Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men. Effect of a high sugar intake on some metabolic and regulatory indicators in young men. Overweight treated with energy restriction and a dietary fibre supplement: A 6-month randomized, double-blind, placebo-controlled trial. Effect of dietary fibre on glucose control and serum lipoproteins in diabetic patients. Dietary fiber, inulin, and oligofructose: A review comparing their physiological effects. The effect of test meal monounsaturated fatty acid:saturated fatty acid ratio on postprandial lipid metabolism. International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food con sumption. A dietary fibre supple ment and weight maintenance after weight reduction: A randomized, double blind, placebo-controlled long-term trial. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. Effect of high-fat and low-fat diets on voluntary energy intake and substrate oxidation: Studies in identical twins consuming diets matched for energy density, fiber, and palatability. An ecological study of the relationship between dietary fat intake and breast cancer mortality. Lack of effect of a low-fat, high fiber diet on the recurrence of colorectal adenomas. Studies on the mechanism of improved glucose control during regular exercise in type 2 (non-insulin-dependent) diabetes. Macronutrients and plasma triglycerides, high-density lipoprotein, and the ratio of total to high-density lipoprotein cholesterol in women: the Framingham Nutrition Studies. Dose?response effects of dietary marine oil on carbohydrate and lipid metabolism in normal subjects and patients with hypertriglyceridemia. Is relationship between serum choles terol and risk of premature death from coronary heart disease continuous and graded? A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. Cancer risk in relation to fat and energy intake among Hawaii Japanese: A prospective study. Hypotensive effect of low-fat, high-carbohydrate diet can be independent of changes in plasma insulin concentrations. Covert manipulation of the ratio of dietary fat to carbohydrate and energy density: Effect on food intake and energy balance in free-living men eating ad libitum. Covert manipulation of the dietary fat to carbohydrate ratio of isoenergetically dense diets: Effect on food intake in feeding men ad libitum. Deteriora tion in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians. Effect of omega 3 and omega 6 fatty acids on transformation of cultured cells by irra diation and transfection. The prevalence of diabetes mellitus in a traditional-living Polynesian population: the Wallis Island Survey. Comparison of the effects of a mono unsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects. Trichopoulou A, Katsouyanni K, Stuver S, Tzala L, Gnardellis C, Rimm E, Trichopoulos D. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. Dietary fiber, vegetables, and colon cancer: Critical review and meta-analyses of the epidemiologic evidence. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. Tzonou A, Hsieh C-C, Polychronopoulou A, Kaprinis G, Toupadaki N, Trichopoulou A, Karakatsani A, Trichopoulos D. A prospective cohort study on dietary fat and the risk of postmenopausal breast cancer. Influence of diets con taining casein, soy isolate, and soy concentrate on serum cholesterol and lipo proteins in middle-aged volunteers. Dietary fat intake and risk of lung cancer: A prospective study of 51,452 Norwegian men and women. Dietary fat intake and risk of prostate cancer: A prospective study of 25,708 Norwegian men. Dietary fat, fat subtypes, and breast cancer in postmenopausal women: A prospective cohort study. Diet restriction increases ubiquinone contents and inhibits progression of hepatocellular carcinoma in the rat. Boys from populations with high-carbohydrate intake have higher fasting tri glyceride levels than boys from populations with high-fat intake. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. Relationship of distance run per week to coronary heart disease risk factors in 8283 male runners. Does weight loss cause the exercise-induced increase in plasma high density lipoproteins? Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moder ately overweight men. Second-meal effect: Low-glycemic-index foods eaten at dinner improve subsequent break fast glycemic response. Replacement of carbohydrate by protein in a conven tional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects. Changes in plasma lipids and lipoproteins in overweight men dur ing weight loss through dieting as compared with exercise. Effect of dose and modification of viscous properties of oat gum on plasma glucose and insulin following an oral glucose load. Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects. Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. Effect of energy restriction on tissue size regulation during chemically induced mammary carcinogenesis. The term tolerable is chosen because it connotes a level of intake that can, with high probability, be tolerated biologically by individuals; it does not imply acceptability of that level in any other sense. Many individuals are self-medicating with nutrients for curative or treatment purposes. It is beyond the scope of this report to address the possible therapeutic benefits of higher nutrient intakes that may offset the risk of adverse effects. The term adverse effect is defined as any significant alteration in the structure or function of the human organism (Klaassen et al. Any such alteration (referred to as an adverse nutrient?nutrient interaction) is considered an adverse health effect. This does not mean that there is no potential for adverse effects result ing from high intake. When data about adverse effects are extremely limited, extra caution may be warranted. Like all chemical agents, nutrients can produce adverse health effects if their intake from a combination of food, water, nutrient supplements, and pharmacological agents is excessive. Some lower level of nutrient intake will ordinarily pose no likelihood (or risk) of adverse health effects in normal individuals even if the level is above that associated with any benefit. It is not possible to identify a single risk-free intake level for a nutrient that can be applied with certainty to all members of a population. However, it is possible to develop intake levels that are unlikely to pose risk of adverse health effects for most members of the general population, including sensitive individuals. For some nutrients, these intake levels may pose a risk to subpopulations with extreme or distinct vulnerabilities. Such a model might have several potential advantages, including ease of application and assur ance of consistent treatment of all nutrients. It was concluded, however, that the current state of scientific understanding of toxic phenomena in general, and nutrient toxicity in particular, is insufficient to support the development of such a model. Scientific information about various adverse effects and their relationships to intake levels varies greatly among nutri ents and depends on the nature, comprehensiveness, and quality of avail able data. The uncertainties associated with the unavoidable problem of extrapolating from the circumstances under which data are developed. The hallmark of risk assessment is the requirement to be explicit in all of the evaluations and judgments that must be made to document conclusions. The characterization of risk typically contains both qualitative and quantitative information and includes a discussion of the scientific uncertainties in that information.

It has recently been concluded that there may be no need to restrain dietary protein intake mens health positions buy proscar 5 mg on-line. Poor protein status itself leads to bone loss man health shop buy generic proscar canada, whereas increased protein intake may lead to increased calcium intake prostate relief order genuine proscar line, and bone loss does not occur if calcium intake is adequate (Heaney prostate verb purchase proscar online, 1998) mens health rs order proscar with a visa. In a recent prospective study of men and women aged 55 to 92 years prostate location cheap proscar online amex, consumption of animal protein was positively associated with bone mineral density in women, but not in men (Promislow et al. In contrast, Dawson-Hughes and Harris (2002) reported no association between protein intake and bone mineral density in 342 healthy men and women aged 65 years and older. However, when the individuals were given cal cium citrate malate and vitamin D in addition to the high protein intake, there was a favorable change in bone mineral density. Kidney Stones It has been estimated that 12 percent of the population in the United States will suffer from a kidney stone at some time (Sierakowski et al. The most common form of kidney stone is composed of calcium oxalate, and its formation is promoted by high concentrations of calcium and oxalate in the urine. A high animal protein intake in healthy humans increases urinary calcium and oxalate and the overall probability of form ing kidney stones by 250 percent (Robertson et al. Conversely, restricting protein intake improved the lithogenic profile in hypercalciuric patients (Giannini et al. Also, the incidence of calcium oxalate stones has been shown to be associated with consumption of animal pro tein (Curhan et al. In this study, 50 patients were given low animal protein (56 to 64 g/d) and high fiber, plus adequate fluid and calcium, whereas 49 control patients were only instructed to take adequate water and calcium. However, as protein intake was not the only variable, and in view of the data described above suggesting benefits from lower protein intake, further investigation is necessary. Renal Failure Restriction of dietary protein intake is known to lessen the symptoms of chronic renal insufficiency (Walser, 1992). This raises two related, but distinct questions: Do high protein diets have some role in the develop ment of chronic renal failure? The concept that protein restriction might delay the deterioration of the kidney with age was based on studies in rats in which low energy or low protein diets attenuated the develop ment of chronic renal failure (Anderson and Brenner, 1986, 1987). In particular, the decline in kidney function in the rat is mostly due to glomerulosclerosis, whereas in humans it is due mostly to a decline in filtration by nonsclerotic nephrons. Also, when creatinine clearance was measured in men at 10 to 18-year intervals, the decline with age did not correlate with dietary protein intake (Tobin and Spector, 1986). Correla tion of creatinine clearance with protein intake showed a linear relation ship with a positive gradient (Lew and Bosch, 1991), suggesting that the low protein intake itself decreased renal function. These factors point to the conclusion that the protein content of the diet is not responsible for the progressive decline in kidney function with age. Coronary Artery Disease It is well documented that high dietary protein in rabbits induces hypercholesterolemia and arteriosclerosis (Czarnecki and Kritchevsky, 1993). However, this effect has not been consistently shown in either swine (Luhman and Beitz, 1993; Pfeuffer et al. In humans, analysis of data from the Nurses? Health Study showed an inverse relation ship between protein intake and risk of cardiovascular disease (Hu et al. The association was weak but suggests that high protein intake does not increase the risk of cardiovascular disease. Obesity A number of short-term studies indicate that protein intake exerts a more powerful effect on satiety than either carbohydrate or fat (Hill and Blundell, 1990; Rolls et al. However, some epi demiological studies have shown a positive correlation between protein intake and body fatness, body mass index, and subscapular skinfold (Buemann et al. In contrast, a 6-month randomized trial demonstrated that the replacement of some dietary carbohydrate by protein improved weight loss as part of a reduced fat diet (Skov et al. Cancer the fact that the growth of tumor cells in culture is often increased by high amino acid concentrations (Breillout et al. Reviews of the literature on colon cancer have concluded that high meat intake may be associated with increased risk, but that high total protein intake is not (Clinton, 1993; Giovannucci and Willett, 1994; Parnaud and Corpet, 1997). A lack of cor relation with total protein intake has been found in a case-control study (Slattery et al. For breast cancer, the geographical distribution of incidence is corre lated with the availability of dietary protein, especially animal protein (Clinton, 1993). Furthermore, migration to an area with typically higher protein intakes is associated with increased risk of breast cancer (Buell, 1973; Buell and Dunn, 1965). In accord with this, several studies have indicated an association among breast cancer and the intakes of animal protein and fat (Hislop et al. However, others showed a relationship with fat, but not protein intake (Miller et al. More recently, a case-control study on 2,569 patients and 2,588 controls showed a slightly negative relationship between total protein and breast cancer (Decarli et al. For other types of tumors, there also is no clear indication of greater risk with higher protein intakes. Total protein intake was not associated with increased risk of lung cancer (Lei et al. Moreover, in some of these studies, there was an inverse relationship with total protein intake (Barbone et al. On the other hand, higher protein intake was associated with an increased risk of cancer of the upper digestive tract (De Stefani et al. Overall, despite the demonstration of a positive influence of dietary fat and total energy, as well as meat (especially red meat), on some types of tumors, no clear role for total protein has yet emerged. The current state of the literature, therefore, does not permit any recommendation of an upper limit to be made on the basis of cancer risk. Oxidation of low density lipoproteins: Intraindividual variability and the effect of dietary linoleate supplementation. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. The aging kidney: Structure, function, mecha nisms, and therapeutic implications. A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Food and Nutrient Intakes by Individuals in the United States, by Sex and Age, 1994?96. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. Dietary fat and risk of coronary heart disease in men: Cohort follow up study in the United States. The role of low-fat diets in body weight control: A meta-analysis of ad libitum dietary intervention studies. Atherogenic lipoprotein phenotype: A proposed genetic marker for coronary heart disease risk. Dietary protein, growth and urea kinetics in severely malnourished chil dren and during recovery. Improved plasma cholesterol levels in men after a nutrition educa tion program at the worksite. Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: Emerging evidence for their role as risk modifiers. Coronary heart disease in Hawaii: Dietary intake, depot fat, ?stress,? smoking, and energy bal ance in Hawaiian and Japanese men. Impaired cellular insulin bind ing and insulin sensitivity induced by high-fructose feeding in normal subjects. Diet and the development of noninsulin-dependent diabetes mellitus: An epidemio logical perspective. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). Effects of diets rich in monounsaturated fatty acids on plasma lipopro teins?The Jerusalem Nutrition Study. The impact of the Guidelines for a Healthy Diet of the Netherlands Nutrition Council on total and high density lipoprotein cholesterol in hyper cholesterolemic free-living men. Dietary fat and the control of energy intake: Evaluating the effects of fat on meal size and postmeal satiety. Effects of changes in palatability on food intake and the cumulative food intake curve in man. Habitual fish consumption, plasma phospholipid fatty acids, and serum lipids: the Tromso Study. Bonanome A, Pagnan A, Biffanti S, Opportuno A, Sorgato F, Dorella M, Maiorino M, Ursini F. Effect of dietary monounsaturated and polyunsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification. Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects. The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. Effects of differences in dietary fat on growth, energy and nutrient intake from infancy to eight years of age. Effect of dietary fat and cholesterol on plasma lipids and lipoprotein fractions in normolipidemic men. Response to a diet low in total fat in women with postmenopausal breast cancer: A pilot study. Quan titative changes in dietary fat intake and serum cholesterol in women: Results from a randomized, controlled trial. Conjugated linoleic acid inhibits differentiation of pre and post-confluent 3T3-L1 preadipocytes but inhibits cell proliferation only in preconfluent cells. Serum lipoproteins of healthy persons fed a low-fat diet or a polyunsaturated fat diet for three months. Effects of saturated and polyunsaturated fat enriched diet on the skeletal muscle insulin sensitivity in young rats. Social class interacts with the associa tion between macronutrient intake and subcutaneous fat. Diet intervention methods to reduce fat intake: Nutrient and food group composition of self-selected low-fat diets. Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: Effects on proliferation and apoptosis. Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China Study. Daily dietary fat and total food-energy intakes?Third National Health and Nutrition Examination Survey, Phase 1, 1988?91. Antibody affinity and immune complexes after immunization with tetanus toxoid in protein-energy malnutrition. Effect of moderate levels of dietary fish oil on insulin secretion and sensitivity, and pancreas insulin content in normal rats. Effect of short-term consumption of a high fat diet on glucose tolerance and insulin sensitivity in the rat. The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. Heart rate vari ability and fatty acid content of blood cell membranes: A dose-response study with n-3 fatty acids. Dietary lipids and blood cholesterol: Quantitative meta-analysis of metabolic ward studies. Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans. Patterns of weight change and their relation to diet in a cohort of healthy women. Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines. Coudray C, Bellanger J, Castiglia-Delavaud C, Remesy C, Vermorel M, Rayssignuier Y. Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Deleterious metabolic effects of high-carbohydrate, sucrose-containing diets in patients with non-insulin-dependent diabetes mellitus. A prospective study of dietary calcium and other nutrients and the risk of kidney stones in men: 8 Year follow-up. Calcium intake influences the association of protein intake with rates of bones loss in elderly men and women. Macronutrients, energy intake, and breast cancer risk: Implications from different models. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Mediter ranean diet, traditional risk factors, and the rate of cardiovascular complica tions after myocardial infarction. Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy diges tive balance in the rat. Effects of feeding fermentable carbo hydrates on the cecal concentrations of minerals and their fluxes between the cecum and blood plasma in the rat.

The examiner indicates which condition to check for each line of the Clinical Description mens health shoulder workout order 5 mg proscar amex. The examiner may wish to look at the form directly and call off the number of the circle to be marked prostate oncology questions discount 5 mg proscar mastercard. If the examiner wants the recorder to record additional information mens health 4 week fat loss plan cheap 5mg proscar with visa, it should be recorded in the comments section prostate oncology kansas trusted 5mg proscar. The following lesions identified by an S under Clinical Diagnosis are to be smeared for candidiasis mens health 10k edinburgh buy proscar 5 mg free shipping. At the top of page 3 under smear prostate cancer biopsy procedure order proscar us, mark "Y" or "N" to indicate whether or not the smear was taken. Angular cheilitis Candidiasis Denture stomatitis Erythroplakia Leukoplakia Lichen Planus Median Rhomboid glossitus Referral 5-37 5. There are three parts to the dental caries examination: coronal caries, root surface caries and baby bottle tooth decay. For children ages 12-24 months, the presence of dental caries on the four maxillary incisors will be noted. For all age groups 2-6 years, the presence of baby bottle tooth decay will be determined from the coronal caries examination findings for deciduous teeth. An examiner should avoid the temptation to examine more thoroughly a subject who appears to be highly susceptible to caries, or less thoroughly a person who appears less susceptible. The caries examination sequence should follow the sequence shown on the data forms. The forms are arranged by quadrants; the examiner starts with the upper left central incisor and continues distally through the second molar in the same quadrant. The same sequence is followed for the upper right, lower left, and lower right quadrants. At the end of each quadrant the examiner notes the presence or absence of the third molar for that quadrant. Tooth surfaces are examined in the following order: lingual, labial, mesial, and distal for anterior teeth, and occlusal, lingual, buccal, mesial, and distal for posterior teeth. It is not advisable to call out individual surface codes as each tooth surface is examined, as this can be confusing to the recorder. It is better for the examiner to mentally accumulate surface calls for a given tooth until all surfaces have been examined before dictating the calls to the recorder. Frank lesions are detected as gross cavitation and thus present few problems in diagnosis. Incipient lesions, on the other hand, are more difficult to diagnose consistently. Incipient lesions may be subdivided into three categories according to location, each with the following special diagnostic considerations: 1. Pits and fissures on occlusal, buccal and lingual surfaces: these areas are diagnosed as carious when the explorer catches after insertion with moderate, firm pressure and when the catch is accompanied by one or both of the following signs of caries: a. Opacity adjacent to the area providing evidence of undermining or demineralization. In other words, a deep pit or fissure in which the explorer catches is not in itself sufficient evidence of decay; it must be accompanied by at least one of the above signs. Smooth areas on buccal (labial) or lingual surfaces: these areas are carious if they are decalcified or if there is a white spot as evidence of subsurface demineralization and if the area is found to be soft by: a. These areas should be diagnosed as sound when there is only visual evidence of demineralization. Proximal surfaces: For areas accessible to direct visual and tactile examination, as when there is no adjacent tooth, the criteria are the same as those for smooth areas on facial or lingual surfaces. In anterior teeth only, transillumination can serve as a useful aid in discovering proximal lesions. Transillumination is achieved by placing a mirror lingually and positioning the examining light so that it passes through the teeth and reflects into the mirror. If a characteristic shadow or loss of translucency is seen on the proximal surface, then this is indicative of caries on the surface. Ideally, the actual diagnosis should be confirmed by detecting a break in the enamel surface with the explorer; however, clear visualization of a lesion by transillumination can justify a positive diagnosis. In posterior teeth, however, visual evidence alone, such as undermining under a marginal ridge, is not sufficient proof for diagnosing a proximal 5-41 lesion. A positive diagnosis is made only if a break in the enamel surface can be detected with the explorer. This component traditionally represents those permanent teeth that have been extracted only as a result of caries. However, because of the difficulty of correctly distinguishing between teeth extracted due to caries and those extracted for periodontal reasons, no attempt will be made at the time of the examination to differentiate between these two causes of tooth loss. It is essential, however, to distinguish between teeth extracted because of caries or periodontal disease and those extracted or missing for other reasons. The code "E" will be used to indicate teeth extracted because of caries or periodontal disease, and a different code, "M", will be used for teeth missing due to trauma, orthodontic treatment, or other non-disease related causes. Unerupted or congenitally missing teeth (code "U") must also be correctly identified. When a replacement exists, the examiner will not consider its condition or adequacy when making the call. When a replacement does not exist, the examiner will not attempt a clinical judgment of the need or adequacy of space for a replacement, even if the space has been closed by tooth movement. When more than one tooth has been replaced by a single pontic, each tooth space will be scored as replaced. Note: the "R" designator is used only in conjunction with the "E" and "M" scores, and consequently does not apply to the deciduous dentition, or to unerupted teeth (code "U"). The F component represents a tooth surface that has been filled with either a permanent or a temporary restoration as a result of caries involvement. Here also it is necessary to distinguish between surfaces restored for caries and those restored for other reasons, such as trauma, hypoplasia, malformation, or bridge abutment. The following conventions have been adopted in the interest of achieving diagnostic consistency: 1. If a lesion or restoration is confined solely to the incisal edge its score should be assigned to the nearest adjacent surface. Thus, anterior teeth have only four scorable surfaces (mesial, distal, labial, and lingual). The inclusion of the occlusal surface for posterior teeth gives those teeth five surfaces. When a caries lesion extends beyond the line angle onto another surface, that surface is also scored as carious. For restorations, however, the following rules apply: On anterior teeth, a proximal filling is not considered to involve the adjacent labial or lingual surface unless it extends at least one-third of the distance to the opposite proximal surface. The reason for this criterion is that tooth structure on labial or lingual surfaces of anterior teeth must often be removed to provide access for the proximal restoration. On posterior teeth, to guard against a similar possibility of overcalling, a proximal restoration should extend more than a millimeter past the line angle before it is considered to involve the adjacent buccal or lingual surface. If a permanent tooth has a full crown restoration placed because of caries, the tooth will be coded as C, which represents the maximum number of surfaces for the tooth type, i. By convention, all full crowns on posterior teeth, including abutment teeth for fixed or removable prostheses, are considered to have been placed as a result of caries. On anterior teeth, however, the examiner should make a determination of the reason for crown placement. If it can be determined that the crown was placed solely for a reason other than caries, such as fracture, malformation or bridge abutment, the tooth is coded Y. However, when the crown coverage extends onto the buccal (labial) or lingual surface for cusp protection, the surface is not scored as restored unless the coverage extends more than two millimeters cervically from the cusp tip or incisal edge. For three-quarter crowns used as abutment teeth, all surfaces are scored in the usual manner if the abutment is a posterior tooth. On anterior teeth, if it can be determined that the crown was placed solely for purposes of abutment and not for caries, the restoration will not be scored, but surfaces without crown coverage will be examined and scored in the usual manner. Teeth that are banded or bracketed for orthodontic treatment are examined in the usual manner and all visible surfaces are scored. Certain teeth, notably first bicuspids, may have been extracted as part of orthodontic treatment. The examiner must make the determination that the teeth were in fact extracted for orthodontic reasons, although this is not usually difficult because of the typically symmetric pattern of these extractions. For the sake of uniformity, all orthodontically extracted bicuspids are scored as first bicuspids. In many cases the subject will have good recall of the reason for the extractions, and can help in making the correct determination. If, however, a restoration on a non-vital tooth was placed solely to seal a root canal and not for caries, that restoration will not be scored. If no other lesions or restorations are present, the tooth will be called sound (S). However, if it can be determined that a restoration on such a tooth was placed solely for esthetic reasons and not for caries, that restoration will not be scored. Malformed teeth are scored in the usual manner except when they have been restored with a full crown for esthetic reasons, in which case they are coded Y. When the tooth crown is destroyed by caries and only the roots remain, score all surfaces carious (X, 0, 1, 2, 3 on posterior teeth and 0, 1, 2, 3 on anteriors). When the same tooth surface is both carious and filled, only the caries is scored. Fractured or missing restorations are scored as if the restoration were intact unless caries is found to be present. If both a deciduous and a permanent tooth occupy the same tooth space, only the permanent tooth is scored. When examining second molars it is important to note that a drifted third molar may occupy the space of a missing second molar. In such cases, the diagnosis and score must relate to the status of the missing second molar, not the third molar. If the second molar, for example, was extracted due to caries and the space is now occupied by a sound third molar, the second molar is scored as extracted (E) and the third molar is not scored. A tooth is considered to be in eruption when any part of its crown projects through the gum. This criterion is easier to standardize than one based on a more advanced stage of eruption. Stain and pigmentation alone should not be regarded as evidence of caries as either can occur on sound teeth. Decayed or filled surfaces of deciduous teeth are scored in the same manner as permanent teeth, using the same diagnostic criteria. However, because this survey is concerned with both deciduous and permanent teeth, it will be necessary to call sound deciduous teeth with a "deciduous" score (D) to distinguish them from sound permanent teeth. The K code will be used for deciduous teeth with restorations or caries and will precede any other legitimate diagnostic call for decayed or filled surfaces. For example, if a deciduous molar has occlusal caries and is otherwise sound, the K code would be combined with the code for occlusal caries. Missing deciduous teeth present potential problems in scoring because it is often not possible to distinguish exfoliated teeth from those extracted due to caries, especially during the period of mixed dentition. To avoid this problem, at the time of examination, all missing deciduous teeth are scored as unerupted permanent teeth (U). When data are analyzed, the age of the subjects can be used to determine the most likely reason for tooth loss. The presence of adhesive fissure sealant is to be recorded for specified posterior teeth and maxillary lateral incisors, using the code A. These teeth are identified on the data form by the letter A, which appears at the middle of the tooth box for the selected teeth. If a permanent tooth is sound and sealed, the A would be called and marked in addition to the S. If the permanent tooth has scores for individual sites, then the A would be called in addition to , and after any other score for the surfaces on that tooth. It is important to be aware that sealant products may vary in appearance, from clear to colored or white. If it appears that sealant material was used as a restoration rather than as a preventive procedure, score the surface as filled and do not record the presence of sealant. Generally, caries in root surfaces occurs coronal to the present gingival margin; very few lesions exist solely in the gingival pocket. Although all exposed root surfaces are susceptible, it has been reported that caries predominantly occurs in approximal and buccal aspects. However, they may spread laterally along the cervical junction, sometimes coalescing with neighboring lesions to produce a collar of caries around the root. Caries that begins in a root surface does not tend to affect the adjacent coronal enamel surface directly. Rather, it may undermine the cervical enamel and invade coronal dentin, leaving a cervical enamel spur or ledge. If the carious process continues, pieces of this ledge may fracture, making it appear as if caries had originated in the enamel as well as the cementum. Subjects should be examined with a sharp, #23, sickle-shaped explorer and unmarred, non magnifying, front surface mirror. The portable chair should be set at a height that is comfortable and compatible with the height of the stool. Instruments and other necessary materials are placed on a table within easy reach of the examiner.

After ten further doublings in 12 volume prostate brachytherapy order proscar 5 mg fast delivery, the tumour would weigh about 1 kilogram (10 cells) prostate cancer blood in urine buy proscar 5 mg with visa, a size that may be lethal to the host androgen hormone yang cheap proscar 5mg with amex. Thus mens health 50 plus generic 5 mg proscar amex, the range of size over which the growth of a tumour may be studied represents a rather short and late part of its total growth history mens health 17 day abs buy proscar 5 mg. Thus prostate cancer zigns generic proscar 5mg without prescription, early clinical detection may be expected to reduce but not to prevent the subsequent appearance of metastases. The proportion of thymidine labeled cells at a short interval after administration of tritiated thymidine (the labeling index) is a measure of the proportion of cells in S phase. Typical values for the proportion of cells in S phase are in the range of 3 to 15 percent for many types of human solid tumours. Higher rates of cell proliferation are evident in faster-growing malignancies, including acute leukemia and some lymphomas. However, the rate of cell proliferation is usually less than that of some cells in normal renewing tissues, such as the intestine or bone marrow. Thus, accumulation of cells in tumours is not due simply to an increased rate of cell proliferation as compared to the normal tissue of origin. Rather, there is defective maturation and the population of malignant cells increases because the rate of cell production exceeds the rate of cell death or removal from the population. Most tumours contain nonproliferating cells, and the term growth fraction describes the proportion of cells in the tumour population that is proliferating. The occurrence of extensive necrosis in solid tumours and of apoptotic cells and the ability of tumour cells to metastasize from a primary tumour indicate that there is considerable cell death or loss from many tumours. The rate of cell loss from tumours can be estimated by 76 comparing the rate of cell production (from assessment of the labeling index or fraction of S phase cells by flow cytometry) with the rate of tumour growth. The overall rate of cell production may be characterized by the potential doubling time of the tumour (Tpot), which is the expected doubling time of the tumour in the absence of cell loss. Flow cytometry: Flow cytometry is a method that allows the separation and sorting of cells based on cellular fluorescence. Flow cytometry can be used to estimate cell cycle phase distribution, growth fraction, and kinetic properties of cell populations. Several methods allow proliferating and nonproliferating cells to be distinguished by flow cytometry. The Ki-67 antigen has been used most often as a marker for proliferating cells although its function remains poorly understood. The mean values of Tpot are also much lower than estimates of volume doubling time for common human tumours (typically 2 to 3 months) because the rate of cell loss in many human tumours is in the range of 75 to 90 percent of the rate of cell production. Not surprisingly, well nourished cells close to blood vessels have a more rapid rate of cell proliferation than poorly nourished cells close to a region of necrosis. Slowly proliferating cells at a distance from functional blood vessels may be resistant to radiation because of hypoxia and to cytotoxic chemotherapeutic drugs because of their low proliferative rate and limited drug access. Initial evidence accrued from analysis of X-linked genes or gene products in cells from tumours in women who are heterozygous at these genetic loci. One of the X chromosomes becomes inactivated at random in all cells of females during early life. The normal tissues of heterozygous females are therefore mosaics that contain approximately equal number of cells in which one or the other (but not both) of the two alleles of a gene on the X chromosomes are expressed. However, cells in tumours arising in such individuals usually express only one allele of such genes?for example they express only one form (isoenzyme) of the X-linked glucose-6-phosphate dehydrogenase. Other clonal markers include chromosomal rearrangements such as the Philadelphia chromosome in chronic myelogenous leukemia; uniquely rearranged immunoglobulins or T-cell receptors expressed by B-cell lymphomas or multiple myelomas and T-cell lymphomas; and molecular markers whose detection has been facilitated by the availability of gene sequencing. The above techniques have demonstrated clonality in at least 95 percent of the wide range of tumours that have been examined. Renewal tissues such as bone marrow and intestinal mucosa represent a hierarchy of cells produced by cell division and differentiation from a small number of stem or early precursor cells. Most tumours arise in renewal tissues, and there is substantial evidence that many tumours contain a limited population of stem cells with the capacity to regenerate the tumour after treatment. Other cells in the tumour population may have lost the capacity for cell proliferation. Recent experiments have suggested that there is a population of cells in some human tumours that express distinct markers on their cell surface and have the properties of stem cells, including self-renewal. The stem cell model has major implications for the treatment of human tumours since cure or long term control requires the eradication of the stem cells. If stem cells represent a small subpopulation within some tumours then short term changes in tumour volume may not reflect the effects of treatment on stem cells. Cell proliferation in normal tissues Cell proliferation in a variety of normal tissues has also been studied using thymidine labeling and flow cytometry. Acute effects of radiation injury are observed in rapidly proliferating tissues, because radiation-damaged cells often die when they attempt mitosis. The cell kinetics of hemopoietic cells in the bone marrow and epithelial cells in the intestine are examples of renewal tissues where cell proliferation is an important determinant of anticancer therapy. Bone marrow: Cells in bone marrow and blood have an orderly progression of differentiation from myeloblasts to polymorphonuclear granulocytes, from pronormoblasts to red blood cells, and from megakaryocytes to platelets. The earlier bone-marrow precursor cells cannot be recognized morphologically, but can be enriched by flow cytometry using fluorescent markers 78 to antigens that are expressed selectively on their surface. The stem cells may undergo self-renewal or may produce progeny that are early precursor cells for lymphocytes or for cells which under appropriate conditions in culture will form colonies containing cells of the granulocyte, erythroid, megakaryocyte, and monocyte series. Thymidine-labeling studies demonstrated that recognizable precursors of granulocytes and red cells are among the most rapidly proliferating cells in the human body, with a mean duration of S phase (Ts) and mean cell cycle time (Tc) of about 12 and 24 hours. Stem cells and other early precursor cells proliferate slowly under resting conditions, and their more rapidly proliferating progeny provide replacement for the normal loss of mature cells. However, stem cells may proliferate rapidly following depletion of more mature functional cells. The pattern of proliferation and differentiation in the bone marrow provides an explanation for the decrease in mature granulocytes at 10 to 14 days after cycle-active chemotherapy and their recovery by 21 to 28 days. The rapidly proliferating intermediate precursor cells are most likely to be killed by chemotherapy but changes in the numbers of cells in the peripheral blood are not seen immediately because the later maturing cells are nonproliferating and tend to be spared by chemotherapy. The bone marrow is generally regarded as the most critical tissue for radiation sensitivity following whole body irradiation due to the sensitivity of the stem cells and doses greater than 6-8 Gy are usually lethal without a bone marrow transplant. Intestine: the villi of the small intestine are lined by a single layer of differentiated epithelial cells that do not proliferate, and cell death and shedding of cells into the lumen occurs at the top of the villi. These cells are replaced by upward migration of cells lining the crypts, which lie between and at the base of the villi. Cell proliferation in the upper two thirds of the crypts is high but occurs more slowly at their bases. Slowly proliferating cells in this region act as precursors for the entire crypt and surrounding villi. Following whole body exposure to radiation, damage to the intestine can be lethal within a few days if the dose is sufficiently high (>10 Gy for humans) 3. Cell death mechanisms Many types of cells do not show morphological evidence of radiation damage until they attempt to divide. Following doses of less than about 10 Gy, lethally-damaged cells may undergo permanent growth arrest (senescence), interphase death or lysis during radiation induced apoptosis, or cell lysis as a result of mitotic catastrophe (often after a number of abortive mitotic cycles). A radiation survival curve based on colony-forming ability represents the total cell death within an irradiated cell population as a result of all types of cell death. For the majority of normal and tumour cells, death secondary to mitotic catastrophe accounts for most of the cell kill following irradiation. However, in some radiosensitive cells and the cancers that arise from them notably lymphocytes, spermatocytes, thymocytes, and 79 salivary gland epithelium?irradiation causes the cells to undergo an early (within a few hours) interphase death. This death is associated with the biochemical and morphologic characteristics of apoptosis. Why some cells undergo extensive radiation-induced apoptosis within a few hours after irradiation, while others do not, is unclear, but may relate to radiation-induced expression of proteins which trigger an apoptotic response. For example, in hematopoietic cells, radiation can lead to upregulation of pro-apoptotic genes (such as fas, bax, and caspase-3) and/or downregulation of anti-apoptotic genes, (such as bcl-2). In the radiation response, ceramide serves as a second messenger in initiating apoptosis, while some of its metabolites block apoptosis. In certain cells, such as endothelial, lymphoid and hematopoietic cells, ceramide mediates apoptosis, while in others ceramide may serve only as a co-signal or play no role in the death response. The ceramide-mediated apoptotic response to radiation can be inhibited by basic fibroblast growth factor. Altering the apoptotic response of tumour cells may be one strategy to sensitize tumours to radiotherapy. Some tumours may evade radiation therapy-induced apoptosis by carrying p53 gene mutations or by lacking p53 expression or function; restoration of wild-type p53 function using gene therapy may potentiate radiation cell kill. However, the induction of apoptosis following irradiation does not account for the therapeutic effect of radiation in solid epithelial tumours, as it does not correlate with eventual clonogenic cell survival as measured by colony-forming assays. Most tumour cell lines have retained the capacity of normal cells to undergo accelerated senescence after irradiation, and although the cell-cycle-related p53 and p21Waf1 genes can act as positive regulators of treatment-induced senescence, they are not required for this response in tumour cells. Senescent or terminal arrested cells are metabolically active but do not proliferate and do not form colonies following irradiation. This may explain the relatively slow resolution, yet ultimate cure, of some tumours following radiotherapy. The random nature of the energy deposition events means that damage can occur in any molecule in a cell. If a cell does survive and goes on to proliferate after irradiation, delayed chromosomal instability may sometimes be observed in its descendants. One factor that seems to perpetuate the unstable phenotype in irradiated cells is the continued production of reactive oxygen species. Such species or other factors may be released from an irradiated cell and cause damage to neighboring nonirradiated cells. For example, transfer of media from irradiated unstable cell clones to a nonirradiated cell population has been reported to lead to cell death in some of the nonirradiated cells within 24 hours. These data are consistent with clinical studies that have shown chromosomal changes in circulating peripheral lymphocytes in patients who received only localized radiotherapy. Similarly the serum from people who have been exposed to whole body irradiation has been reported to be clastogenic for lymphocytes in culture. This bystander effect of radiation has implications for assessment of radiation risk and for health risks associated with radiation exposure as the total cell kill within an irradiated cell population may be greater than that calculated simply on the basis of the number of cells that were directly irradiated. In vitro and in vivo assays for cell survival Inhibition of the continued reproductive ability of cells is an important consequence of the molecular and cellular responses to radiation, as it occurs at relatively low doses (a few grays) and it is the major aim of clinical radiotherapy. A cell that retains unlimited proliferative capacity after radiation treatment is regarded as having survived the treatment, while one that has lost the ability to generate a clone or colony is regarded as having been killed, even though it may undergo a few divisions or remain intact in the cell population for a substantial period. In the assay that is used most often to assess colony formation, cells grown in culture are irradiated either before or after preparation of a suspension of single cells and plated at low density in tissue-culture dishes. Following irradiation, the cells are incubated for a number of days, and those that retain proliferative capacity divide and grow to form discrete colonies of cells. After incubation, the colonies are fixed and stained so that they can be counted easily. If a range of radiation doses is used, then these cell-survival values can be plotted to give a survival curve. The techniques described above have been used to obtain survival curves for a wide range of malignant and normal cell populations. Such semilogarithmic curves usually have a shoulder region at low doses but at higher doses, the curve either becomes steeper and straight so that survival decreases exponentially with dose or appears to be continually bending downward. The accuracy of the experimental data obtained is usually such that either shape could fit the data adequately over the first few decades of survival. The standard type of radiation was usually taken as 200 or 250-kilovolt (peak) X rays, but now Cobalt 60? Many different mathematical models have been used to produce equations that can fit survival-curve data within the limits of experimental error. Two of the more commonly used models are the old target-theory model and the newer linear-quadratic models of cell survival. Cell killing by radiation is now recognized to be more complex, but the equation and parameters derived from the model are still used to describe the shape of cell survival curves (Figure 3. The lesions that interact could be caused by a single ionizing track, giving a direct dependence of cell killing on dose, or by two or more separate tracks, giving a dependence of lethality on higher powers of dose. The assumption that two lesions must interact to cause cell killing gives an equation that can fit most experimental survival curves quite adequately, at least over the first few decades of survival. Such mathematical models are useful when comparing cellular radiosensitivity among a variety of cell types or when the shape of the survival curve is altered following treatment with drugs or changes in the environment. From these models, it has been observed that there is greater variation in the low-dose or shoulder region of the radiation survival curves obtained for mammalian cells as compared to the variation in the slopes of the high-dose region of the curves. Non-clonogenic assays have also been used to estimate the relative radiosensitivity of cells, although assays that measure short term growth or programmed cell death/apoptosis often do not correlate with the longer-term clonogenic assay. Assays for apoptosis may predict clonogenic survival within some cancer cell lines. They are of limited value for radiosensitivity studies because it is rarely possible to assess more than one decade of cell kill and they usually do not correlate with the clonogenic assay. At present, clonogenic survival remains the ?gold standard? for determining the radiosensitivity of cells in vitro. Methods have also been developed for assessing the ability of cells to form colonies in vivo. One of these is the spleen-colony method, which has been used to assess both the radiation and drug sensitivity of bone marrow stem cells. In this assay bone marrow from treated animals is injected into irradiated hosts and colonies from surviving bone marrow stem cells can be then counted in the spleen.

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References

• Ota N, Fujimoto Y, Murata M, et al. Improving outcomes of the surgical management of right atrial isomerism. Ann Thorac Surg. 2012; 93(3):832-9.
• Freeman N, Power C, Rodgers B. Weight-for-height indices of adiposity: Relationships with height in childhood and early adult life. Int J Epidemiol 1995; 24:970-976.
• Mathurin P, Mouquet C, Poynard T, et al. Impact of HBV and HCV on kidney transplantation outcome. Hepatology. 1999;29: 257-263.
• Tsirka SE, Rogove AD, Bugge TH, et al. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 1997;17:543-52.
• Burki T, Hamid R, Ransley PG, et al: Injectable polydimethylsiloxane for treating incontinence in children with the exstrophy-epispadias complex: long-term results, BJU Int 849n853, 2006. Cadeddu JA, Benson JE, Silver RI, et al: Spinal abnormalities in classic bladder exstrophy, Br J Urol 79:975, 1997.