The Painless Stop Smoking Cure

Quit Smoking Cigarette

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Quit Smoking Magic Summary

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Nicotine pharmacology

Nicotine is absorbed through mucous membranes in a highly pH-dependent fashion. The t' 2 is 2 h. It is largely metabolised to inert substances, e.g. cotinine, though some is excreted unchanged in the urine (pH dependent, it is un-ionised at acid pH). Cotinine is used as a marker for nicotine intake in smoking surveys because of its convenient t1 , (20 h). 15 Tobacco Advisory Group, Royal College of Physicians 2000 Nicotine addiction in Britain. London RCP.

Lung Cancer As A Model System

We have chosen lung cancer as a model in which to investigate the association of antinuclear antibodies and oncogenesis for a number of reasons. First, lung cancer is the most frequently diagnosed cancer in the world, and is the most common cause of cancer deaths in men and women in the US and worldwide, representing 28 of all cancer deaths in the US 44 , The majority of people with lung cancer will die within 1 year of its detection. This high mortality rate can in part be attributed to lack of diagnostic methods that allow early detection. New molecular markers, such as autoantibodies to a defined set of antigens, that lead to an earlier diagnosis and treatment are likely to improve survival. Second, one of the mutagens in cigarette smoke has been identified as the prime etiologic factor responsible for the disease. There is good evidence that exposure to a particular mutagen gives rise to molecular lesions characteristic of that mutagen. Tobacco-specific TV-nitrosamines are known...

Smoking Cessation in Patients with Coronary Heart Disease

Patients with CHD who smoke can halve their risk for a recurrent CHD event22 if they quit smoking. Although physicians and patients may both be aware of this fact, smoking cessation is not easily achieved. Surveys within the framework of the EUROASPIRE project revealed that in the year 2000 on average 21 of CHD patients in Europe smoked (had continued their smoking or had taken it up again after their CHD event).23 EUROASPIRE data from M nster have shown that evidence-based smoking cessation procedures such as nicotine replacement therapy and behavioral therapy are seldom practiced by cardiologists. Of the 64 CHD patients who smoked in the EUROASPIRE M nster study of the year 2000 only 6 ( 4) reported that their physician had prescribed a nicotine replacement therapy. An independent survey of 681 ambulatory care physicians of the M nster region24 revealed that only 16 of them were in favor of smoking cessation courses and only 5 had prescribed nicotine replacement therapy to their...

The Role of Tobacco Dependence and Addiction

Most smokers do want to quit smoking. That this is not always an easy task can be attributed to the fact that dependence plays an important role. Nicotine dependence meets all criteria of addiction. The use is compulsive, it is hard to quit even when there is clear damage,withdrawal symptoms appear when stopping, and there is always a risk of falling back when trying to quit a chronic behavior. Smoking dependence fits the criteria given in the Diagnostic and Statistical Manual of Mental Disorders system, version IV (DSM IV),1 grading dependence and addiction to a substance (Table 28-1). The estimated percentage of smokers who are addicted varies from 50 to 92 .2,3 Yearly, about half of all smokers are planning to quit and about 25 are taking action to quit smoking. Only 7 of these attempts to quit are successful.4 Tobacco smoke consists of more than 2000 different substances, among which are gases and a very fine mixture of tar (solid and liquid substances). Nicotine is the main...

Wnt Signaling in Stem Cells and Lung Cancer

Lung Cell Development Wnt Signaling

2 Stem Cells, Cancer Stem Cells, and Lung Cancer 31 4 Wnt Signaling in Lung Cancer 37 2 Stem Cells, Cancer Stem Cells, and Lung Cancer Lung cancer is the leading cause of cancer mortality in the USA. Approximately 173,770 new cases of lung cancer were diagnosed in 2004,13 of all new cancer cases, and an estimated 160,440 Americans died from the disease, accounting for 28 of all cancer deaths. There are two major pathological groups in lung cancer non-small cell lung cancer (NSCLC), comprising 80 of the total, and small cell lung cancer (SCLC) comprising the remaining 20 . Increasing evidence shows that lung cancer occurs through a multistep oncogenic process. Bronchioalveolar carcinoma (BAC) and atypical adenomatous hyperplasia (AAH), a premalignant lesion believed to be a precursor to BAC, are often present near areas of invasive adenocarcinoma (Yoshida et al. 2005 Saad et al. 2004 Kitamura et al. 1999 Okubo et al. 1999). Both tumor suppressor genes and oncogenes play important roles...

Nicotine Replacement Therapy

Before starting the nicotine replacement therapy the user has to quit smoking. Nicotine replacement therapy provides an alternative form of nicotine to relieve symptoms of withdrawal in a smoker who is abstaining from tobacco use.8 The pharmacokinetic properties of available products differ, but none deliver nicotine as fast as does inhaling nicotine. The patch provides a relatively stable, fixed dose of nicotine over a period of 16 or 24 hours. The other products have a more rapid onset and a shorter duration of action, allowing the user to adjust the dose of nicotine. Blood nicotine levels peak 5 to 10 minutes after the adminis- Advise emphatically advise him or her to stop smoking Advise the smoker to stop smoking, in a clear, strong, and person-specific manner. Assess establish the willingness to stop smoking Implement prompts for health professionals to systematically inquire about smoking behavior, for example stickers on the status or by placing a reminder in the patient's...

On The Applied Side Schedules Of Reinforcement Of Abstinence From Cigarette Smoking

In an investigation of cigarette smoking, Roll, Higgins, and Badger (1996) assessed the effectiveness of three different schedules of reinforcement for promoting and sustaining drug abstinence. These researchers conducted an experimental analysis of cigarette smoking because (a) cigarettes can function as reinforcers, (b) smoking can be reduced by reinforcement of alternative responses, and (c) it is relatively more convenient to study cigarette smoking than illicit drugs. Furthermore, cigarette smokers usually relapse within several days following abstinence. This suggests that reinforcement factors regulating abstinence exert their effects shortly after the person stops smoking, and it is possible to study these factors in a short-duration experiment. Sixty adults, who smoked between 10 and 50 cigarettes a day, took part in the experiment. The smokers were not currently trying to give up cigarettes. Participants were randomly assigned to one of three groups progressive...

Smallcell Lung Cancer

Most patients with small-cell lung cancer (SCLC) respond to chemotherapy, but such responses are usually of relatively short duration, and survival has not significantly increased over the past two decades, either in limited or in extensive disease. These discouraging results prompted the investigation of high-dose chemotherapy with autologous stem cell transplant (ASCT) in the early 1980s. Initial studies testing one or two high-dose chemotherapy cycles as front-line therapy showed no improvement in outcome compared to historical controls.39-42 Subsequently, delayed highdose chemotherapy with ASCT was tested as consolidation therapy for a response obtained with conventional-dose chemotherapy. Spitzer et al.43 reported

Nicotine Pharmacodynamics

Pharmacodynamics Nicotine

It is not only due to the pharmacokinetic properties of nicotine administered by smoking, mentioned earlier, that nicotine is as addicting as it is, its pharmacodynamics play an important role as well. Nicotine interacts with the nicotinic cholinergic receptors in both the central and peripheral nervous system. The effect of nicotine can be stimulating but in a high dose it can be dampening too, due to complex electrochemical processes. Smokers report many different pleasant, rewarding effects of their habit, such as arousal, relaxation (especially in stressful situations), improved attention, and an increased performance on certain tasks. Furthermore,nicotine can improve one's mood, reduce anxiety, relieve hunger, and prevent weight gain. Benowitz has linked these positive effects in a (hypothetical) model shown in Figure 28-2.8 Figure 28-1. The nicotine level in blood after smoking one cigarette an hour. Blood samples every 15 minutes. The vertical axis shows the nicotine level in...

Pharmacotherapy for Smoking Cessation

Quitting smoking is one of the primary lifestyle changes that reduce the risk of cardiovascular disease in primary and secondary prevention. However, the addictive nature of nicotine makes smoking cessation difficult to initiate, and withdrawal symptoms, including cravings for cigarettes, make continued abstinence difficult to maintain. Studies show that the majority of serious quit attempts will fail within 1 year.67 This is understandable in the light of evidence showing that cigarette dependence produces long-lasting structural and functional changes in the central nervous system.67,68 Fortunately a number of drug therapies have been established as first-line therapies to aid smoking cessation. Fewer therapies have been shown to be effective in the maintenance of cessation.69 Nicotine replacement therapy (NRT) and bupropion are two pharmacotherapeutic options that are recommended as first-line treatments for motivated smokers trying to quit.67,70 The recommended duration of therapy...

New Approach To Identifying Informative Autoantibodies Associated With Lung Cancer

We have devised an alternative strategy to identify autoantigens associated with lung cancer, with the goal of first focusing our attention on those that have the most potential to be informative. Our method first aims to identify the antinuclear autoantibodies that show significant association with diagnosis, cancer cell type, or patient outcome. Once identified, nuclear antigens can be cloned from either a HeLa cDNA library, the most appropriate lung cell library, or in combination with the SEREX approach, from a library constructed from autologous tumor cDNA. In a pilot study, the sera of 64 lung cancer patients and 64 subjects without a history of cancer were retrospectively tested for reactivity on immunoblots of nuclear extracts of HeLa, small cell carcinoma, squamous cell carcinoma, adenocarcinoma, large cell carcinoma of the lung and normal lung cells 54 , Demographics as well as clinical characteristics of these groups have been reported 55 , All IgG and IgM reactivities...

Nonsmall Cell Lung Cancer

Carcinoma of the lung is the most common cause of death due to cancer in both men and women. Lung cancer can be divided into two fundamental types small cell lung cancer (which is synonymous with oat cell lung cancer) and nonsmall cell lung carcinoma. The differentiation is clinically important as small cell lung carcinoma has a much lower survival rate than nonsmall cell carcinoma. the most frequent histologic type, responsible for 50 of lung cancers. Squamous cell is the next most frequent cancer accounting for 30 , and small cell lung cancer represents 15 . Large cell cancer makes up less than 5 .

The Autoimmune Response In Lung Cancer Is Similar To That In The Systemic Autoimmune Diseases

Predicting ability of antinuclear antibodies. (The ability of antinuclear antibodies to predict lung cancer cell type, diagnosis, or progression-free survival were analyzed by cross-validated CART) Lung cancer diagnosis nm60, ami 15, nm200, hm55, lgl60, ag75, smlOO, agl80, A characteristic profile of autoantibodies is found in each of the systemic autoimmune diseases. These autoantibodies are helpful in establishing a correct diagnosis and prognosis and frequently facilitate the follow-up and treatment of these patients. The value of these antibodies in the diagnosis of the systemic autoimmune diseases is related to their immunologic specificity. Similarly, our data suggest that some of the antinuclear antibodies found in lung cancer sera may be relatively tumor specific and can be predictive of outcome 54 . Autoantibodies frequently precede the onset of a systemic autoimmune disease such as SLE by many years 56 . The report of Frenkel et al. 58 of high titer antinuclear...

Lung Cancer

ANATOMY The lungs are a pair of cone-shaped organs that are part of the respiratory system. The right lung has three sections, called lobes, and is a little larger than the left lung, which has two lobes. When we breathe, the lungs take in oxygen, which our cells need to live and carry out their normal functions. When we exhale, the lungs get rid of carbon dioxide, a cellular waste product. Most lung cancers start in the epithelial lining of the bronchi, and occasionally in the trachea, bronchioles, or alveoli. All forms of lung cancer, being derived from epithelial cells, are carcinomas. RISK FACTORS Scientists have discovered several causes of lung cancer, most due to atmospheric pollutants and the use of tobacco. The smoke from cigarettes, cigars, and pipes contains many compounds called carcinogens that can damage cells, leading to the formation of cancer. The likelihood that a smoker will develop lung cancer is affected by the age at which smoking began, how long the person has...

Tobacco dependence

While psychological dependence is strong and accounts for part of the difficulty of stopping smoking, nicotine possesses all the characteristics of a drug of dependence and there is powerful reason to regard nicotine addiction as a disease. A report on the subject concludes that most smokers do not do so from choice but because they are addicted to nicotine.15 The immediate satisfaction of smoking is due to nicotine and also to tars, which provide flavour. Initially the factors are psychosocial pharmacodynamic effects are unpleasant. But under the psychosocial pressures the subject continues, learns to limit and adjust nicotine intake, so that the pleasant pharmacological effects of nicotine develop

Tobacco Addiction

The burden of cardiovascular disease due to cigarette smoking is enormous, both in the Western world and in developing countries. To stop smoking is healthy at all ages. This section not only focuses on the burden of disease, but also gives information on the latest guidelines to help patients quit smoking, based on the fact that dependency is the main factor that has to be overcome. Therefore, assisting the coronary patient to give up smoking remains one of the main tasks of comprehensive cardiac rehabilitation and all team members should have a basic knowledge in this field.

Smoking Cessation

Peripheral artery disease is particularly high in the smoking male population. To stop smoking therefore is of paramount importance. Smoking cessation slows the progression to critical leg ischemia and reduces the risks of myocardial infarction and death from vascular causes. Although the authors of a meta-analysis of published data concluded that smoking cessation alone did not improve maximal treadmill walking distance,4 smoking cessation programs, nicotine replacement therapy, and the use of anti-depressant drugs such as bupropion should be encouraged.

Cigarette Smoking

Cigarette smoke contains multiple toxins, carbon monoxide, and cancer-causing substances. It is estimated that smoking contributes to about one-third of all cancers, fatal heart attacks, and strokes worldwide. On average, regular cigarette smoking reduces life span by about 10-15 years. Although it is the single most important preventable cause of death in many countries, 20-25 of adults in the USA and Europe continue to smoke. Moreover, many nonsmokers, at work or at home, are exposed to smoke from nearby smokers. Passive smoke can cause asthma, headaches, and many other health problems, and people chronically exposed to passive smoke (such as living with a smoker) increase their risk of cancer by 50-60 . Children are particularly vulnerable to harm from passive smoking. If unable to stop smoking or regularly exposed to passive smoke, the following nutritional guidelines may help reduce the dangers.

Atr Gene Polymorphism And Atherosclerosisrelated Diseases

Coronary artery disease (CAD) is a major public health problem in industrialized countries. Dyslipidemia, arterial hypertension, and diabetes mellitus, the main risk factors for CAD apart tobacco consumption, are influenced by both environmental and genetic factors. Several studies have suggested that the activation of the RAS could be an important contributor to CAD. The best-documented of associations between the occurrence of CAD and polymorphisms in genes RAS component is the I D polymorphism of the ACE gene. After the initial work of Cambien et al. (67), who first suggested the potential role of the ACE D allele as an independent risk factor for myocardial infarction (MI), other case-control studies either confirmed or were in disagreement with their findings (68-70). The M235T variant of AG gene has also been associated with MI but, as in hypertension, with ethnic variability (19). A1166C polymorphism in AT1R gene does not seem to be a direct risk factor for CAD or MI, but, in...

Biological Activity and Side Effects

Tirapazamine shows high selective toxicity (100- to 200-fold) toward hypoxic cells in culture, but its diffusion through tissue is limited by its ready metabolism to the (non-diffusible) radical species (371). Tirapazamine has an ability to kill cells over a much wider range of oxygen concentrations (as high as 2 0,) (372) than most other hypoxia-selective cyto-toxins, so that its activation is not restricted to completely anoxic tissues (373). In animal studies, tirapazamine enhanced the effect of both single-dose (374) and fractionated (375) radiation. Combinations of tirapazamine with both cisplatin (376), cyclophosphamide (377), and other cytotoxic agents, including etopo-side, bleomycin, and paclitaxel (378, 379) showed additive or greater than additive effects on both tumor cell killing and tumor growth delay. Combinations with the blood flow inhibitor 5,6-dimethyl-xanthenone-y-ace-tic acid (DMXAA) showed marked increases in activity in a variety of tumor models (380)....

Newer Concepts Regarding Physiologic Benefits of Exercise Training

A longstanding and attractive hypothesis is the concept that exercise training can reverse or retard the progression of atherosclerosis. The observation that regression of atherosclerosis occurred in animal studies dating back to the 1950s continues to stimulate interest in the effects of exercise on the coronary vasculature in humans. While this idea was largely rejected during the 1970s and 1980s, several notable studies were performed during the 1990s indicating that exercise training, when combined with multidisciplinary risk management, can improve myocardial perfusion.33-35 This has been demonstrated indirectly using nuclear imaging33 and directly by angiography.34,35 Because most of these studies involved multidisciplinary risk reduction (e.g. diet, smoking cessation, stress management, and pharmacologic management of risk factors, including statin therapy) in addition to exercise training, it is not possible to determine the independent effects of exercise training.

Diseases Ofthe Heart And Blood Vessels

Under the age of 65 years smokers are about twice as likely to die of ischaemic heart disease as are nonsmokers, and heavy smokers about 3.5 times as likely. Sudden death may be the first manifestation of CHD and, especially in young men, is related to cigarette smoking. Smoking is especially dangerous for people in whom other risk factors (increased blood cholesterol, high blood pressure) are present. 16 Peto R et al 2000 Smoking, smoking cessation, and lung Atherosclerotic narrowing of the smallest coronary arteries is enormously increased in heavy and even in moderate smokers the increased platelet adhesiveness caused by smoking increases the readiness with which thrombi form. Stopping smoking reduces the excess risk of CHD in people under the age of 65, and after about 4 years of abstinence the risk approximates to that of nonsmokers. Pipe and cigar smokers run little or no excess risk of CHD provided they are not heavy smokers and do not inhale. Heavy cigarette smokers who change...

Interaction With Other Dietary Antioxidants

The potential for the interaction of carotenoids with other antioxidants is discussed in detail in Chapter 3 and only an outline is given here. Truscott (72) first proposed a plausible mechanism for the interaction of vitamins C and E with b-carotene whereby the carotenoid molecule repairs the vitamin E radical reaction (8) and the resulting carotenoid cation radical is, in turn, repaired by vitamin C reactions (9) and (10) . An additive response has been observed for b-carotene and vitamin E, but a synergistic response was only seen when vitamin C was also present (73). If this model is correct then the reduction in the levels of vitamin C in the plasma of smokers compared with nonsmokers (74) is of significance as the repair of any b-carotene radical cations formed would be impaired. A xanthophyll such as zeaxanthin whose conjugated system spans the membrane (see above) would, in theory, be able to interact much more effectively with both lipid- and water-soluble antioxidants than...

Historical Perspectives

Image Stop Smoking

Evidence that chemicals can induce cancer in humans has been accumulating since the sixteenth century (reviewed in Reference 7). In 1567, Paracelsus described a ''wasting disease of miners'' and proposed that exposure to something in the mined ores caused the condition. A similar condition was described in 1926 in Saxony and was later identified as the ''lung cancer of the Schneeberg mines.'' It was realized much later that the cause of this was probably exposure to radon. Nevertheless, Paraclesus could probably be called ''the father of occupational carcinogenesis. It is Bernadini Ramazzini, however, who published a systematic account of work-related diseases in 1700, who is more logically considered the founder of occupational medicine.7

Effects Of Smoking On The Prevalence And Severity Of Periodontal Disease

Controlled clinical studies have demonstrated that in human models of experimental gingivitis, the development of inflammation in response to plague accumulation is reduced in smokers compared with nonsmokers (Table 14-1).(U In addition, cross-sectional studies have consistently demonstrated that smokers present with less gingival inflammation than nonsmokers. svSI These data suggest that smokers have a decreased expression ol clinical inflammation in the presence of plague accumulation when compared with nonsmokers. The microbiologic, immunologic, and physiologic factors that might account for this observation are discussed in detail later. Although gingival inflammation in smokers appears to be reduced in response to plague accumulation when compared with nonsmokers, an overwhelming body of data

Autoantibodies Against Oncoproteins

Lung cancer 10 21 by point mutations, most AAb detect epitopes near the carboxyl terminus of the wild-type protein 17 . In addition to these AAb directed against growth factor receptors (pl85HER-2 neu) or GTP binding proteins (p21ras), AAb to another group of oncoproteins have been described in patients with solid tumors (colorectal, breast, ovary, lung cancer) and patients with leukemias lymphomas. These AAb are directed against nuclear regulatory proteins such as myb and myc 18-23 . However, with the exception of AAb to the L-myc protein, these antibodies have been shown to be relatively unspecific for tumors in some studies (see Table 2). Furthermore, the frequencies of c-myc AAb in healthy volunteers and SLE patients varied greatly in the different studies 18-20 . In general, different methods of AAb determinations and differences in the populations studied may account for varying results. The source and purification of autoantigens and the assays used for AAb determination may...

Autoantibodies To

Cancer testis antigens (CTA) are expressed in a variable proportion of a wide range of human tumors, but are silent in most normal tissues except the testis. Seven CTAs or CTA families have been described up to now (Table 5). They were initially identified as targets for cytotoxic T cells (MAGE, GAGE, BAGE) and, later on, uncovered by SEREX analysis (reviewed in 11,12 ). CTAs identified by SEREX elicited an AAb response in tumor patients. Therefore, this methodology leads not only to the detection of new tumor antigens but also to the identification of specific humoral responses which may be used for diagnostic purposes. Stockert et al. were the first who tested a great number of tumor sera for humoral immune response to SEREX-identified tumor antigens, including several CTAs, by ELISA with recombinant proteins 60 , They showed that 9.4 of melanoma patients, 12.5 of ovarian cancer patients, 4.2 of patients with lung cancer and 7.7 of patients with breast cancer have AAb against...

Treatment of Tobacco Dependency

In most patients the traumatic experience of an acute cardiac event will be the starting point of serious efforts to give up smoking. Here, the engagement, knowledge, and support from all health professionals and the cardiac rehabilitation team is required. After information on the willingness and the stage of change of the patient to stop smoking, the method used to support the patients is described in this chapter, including indications for and use of pharmacotherapy. Insight into smoking addiction, information, support, and understanding are important success factors for the cardiologist in helping the patient to stop smoking and prevent relapse.

Frequency of Smoking in Men and Women in 2002

According to data from the World Health Organization for the year 2002,3 the frequency of smoking in men and women depicts a large variability internationally. Table 27-1 shows for men a range from 67 in China to 19 in Sweden and for women a range from 31 in Germany to 1 in Saudi Arabia. Germany belongs to the countries with the highest percentage of smokers in the world. In the age group 30-39 years about 50 of men and more than 40 of women are smokers. In developed countries we see strong associations between indicators of social status (class) and the frequency of smoking.4 Data from the MONICA Augsburg survey in 1994 95 in men and women, aged 25-74 years, also show strong associations between years of education and cigarette consumption. The higher the number of years of education the lower the percentage of smokers. This finding was true for men of all age groups (25-74 years) and for women of younger age groups (25-44 years).5

Passive Smoking and Cardiovascular Diseases

More than 19 epidemiological studies have focused on passive smoking or second hand smoke and CHD. A meta-analysis by Law et al.16 demonstrated that never-smokers have a 30 higher risk for CHD, if they live with a smoker. Active smoking of one cigarette per day increases the risk for CHD by 39 , which is similar to the risk of a non-smoker who lives with a smoker. Law et al. did not find any bias for this association. The impact of better food habits in non-smokers was estimated to amount to only 6 . If this is taken into account, a risk increase of about 24 for CHD in non-smokers exposed to second hand smoke remains (30 -6 24 ).16 This finding was substantiated by two more recent meta-analyses.17,18

Psychiatric Comorbidity

Smokers more often suffer from psychiatric diseases, namely depression, anxiety disorder and schizophrenia, than do non-smokers. At least 70-90 of all schizophrenia patients smoke.15 There is a clear connection between smoking and depression and anxiety disorders. On the one hand, depression makes smoking lead to nicotine addiction more easily and, on the other hand, smoking promotes the development of depression. The same holds for anxiety and panic disorders. Smoking cessation can cause a temporary aggravation of the depression or anxiety.15

Use in Prevention and Therapy

Pollution and other environmental hazards. Cysteine and glutathione help protect against toxins and pollutants, including drugs, bacterial toxins, peroxidized fats, heavy metals (lead, cadmium, arsenic, etc.), air pollutants, automobile exhaust fumes, food additives, and pesticides.7 Cysteine helps protect the lungs of smokers from the toxic effects of formaldehyde and acetaldehyde, two of the many toxic ingredients in cigarette smoke. Cysteine can be important in cancer chemotherapy, reducing toxicity from agents such as cyclophosphamide and doxorubicin.

Addressing the Patient

Patients who are not motivated to stop smoking should first of all be motivated. Cardiologists and nurses involved should record the smoking behavior and motivational level (Figure 29-1)1 of their patients with a smoking-related disorder and then support motivated smokers in their attempt to stop. This should also include attention and support for the period following discharge from hospital, especially in cardiac rehabilitation programs. Many smokers succeed without aid. Just as various factors may contribute to a some patients getting addicted more quickly to nicotine than others, so some people can stop easily than others. Some smokers can quit smoking after one single advice to stop others will need the help of quit-smoking-groups. The best results are gained by the more intensive forms of support, for example a group course.7 For those who cannot succeed in quitting this way, medication might increase their chance of success. The treatment with medication is preferably combined...

Marine Invertebrates of the Andaman and Nicobar Islands

Siliquariaspongia japonica.239 Two chemotypes of marine bryozoan Bugula neritina were identified.240 A new polysaccharide exhibiting anti-HIV activity and made up of galactan sulfate was isolated from the marine clam Meretrix petechialis241 Dolastatin 15, a potent antineoplastic peptide from the mollusk Dolabella auriculata was undergoing clinical trials in Europe and North America.242 Two sesquiterpenes active against phytopathogenic fungus Cladosporium cucumerinum were isolated from a marine soft coral of the genus Heteroxenia243 A stereocontrolled synthesis of the antitumor agent (-)-laulimalide was achieved.244 Linckosides A and B, the new neuritogenic steroid glycosides were isolated from the Okinawan starfish Linckia laevigata.245 Three alkaloids having an unusual decahydroquinoline skeleton and showing significant and selective antiplasmodial and antitrypanosomal activities, were obtained from a new tunicate species of the genus Didemnum.246 These bioactive alkaloids may serve...

Clinical Correlation

The patient with a history of cigarette smoking and COPD now exhibits long-term carbon dioxide retention, hypoxia, and worsening of respiratory acidosis with incomplete compensation. This is termed acute-on-chronic carbon dioxide retention. The drug testing and patient history revealed excessive intake of OxyContin, a synthetic narcotic, for chronic upper back pain. This medication was causing acute respiratory distress.

Hgf And Met Prognostic Significance

Are potential indicators for prognosis of cancer patients. Yamashita et al (244) extensively analyzed relationships between HGF protein levels in tumour tissues and clinicopathological characteristics in patients with breast cancer. Higher HGF levels in breast tumour tissues correlated well with disease relapse and reduced overall survival, indicating that tissue HGF level is useful prognostic marker in breast cancer patients. Similar findings were noted by other workers (245, 246). Likewise, HGF levels in tissues of non-small cell lung carcinoma (250), gastric cancer (192), and endometrial carcinoma (190), were associated with poor outcome of these diseases. Thus, HGF level is a useful indicator for risk of relapse and short survival time for patients with these cancers. In addition to tissue HGF levels, serum HGF levels were significantly higher in patients with breast cancer (247, 248), gastric cancer (249), and lung cancer (251). Since HGF protein levels in tissues and sera can be...

Production by Lung Hyaluronidases

Hyaluronan is the natural substrate of hyaluronidases, a family of enzymes (54,55) which are discussed in a separate chapter of this book. At least two hyaluronidases are expressed in the lung. They are HYAL1 (56) and HYAL2 (57), which was first described as a product of lung fibroblasts (58) and is expressed in many tissues. Both these enzymes are lysosomal enzymes and they degrade HA differently than testicular hyaluronidase and provide a large piece of approximately 20 kDa. The genes HYAL1, -2 and -3 are located on the chromosomal region 3p21. This region is deleted in many small cell lung cancer lines. In fact, these genes were known as LuCa-1, -2 and -3 before it was realized that hyaluronidases could result from their expression (57). Another peculiarity concerning the lung relates to HYAL2. Rai et al. (59) expressed HYAL2 in NIH 3T3 cells and could not detect hyaluronidase activity, whereas a construct of HYAL1 in the same cell system did produce hyaluronidase. Furthermore,...

Reflectance Measurement of Carotenoids in Skin

300 Chroma Meter

Measurements of large populations with the Raman device have demonstrated a bell-shaped distribution of carotenoid levels in the palm of the hand (89). Field studies have recently been carried out where a population of 1375 healthy subjects could be screened within a period of several weeks (90). Preliminary analysis of the data confirmed that smokers had dramatically lower levels of skin carotenoids as compared to nonsmokers. Furthermore, the study showed that people with habitual high sunlight exposure have significantly lower skin carotenoid levels than people with little sunlight exposure, independent of their carotenoid intake or dietary habits. When analyzed by a chemical assay based on urinary malondialdehyde excretion, an indicator of oxidative lipid damage, people with high oxidative stress had significantly lower skin carotenoid levels than people with low oxidative stress. Again, this relationship was not confounded by dietary carotenoid intakes that were similar in both...

Age And Natural History Of Cancer

Lung cancer, non small cell In the case of non-small cell lung cancer a more indolent course is suggested by reports from different centers that lung cancer presented at an earlier stage in older than in younger individuals 37-39. These reports may be fraught a referral bias, however, as only older patients with resectable tumors might have been referred to the centers for treatment. It is possible that lung cancer after age 70 involved preferentially ex-smokers, in whom reduced exposure to tobacco smoke resulted in more indolent tumors. While several studies have shown that age is associated with decreased treatment response and survival in women with ovarian cancer, the mechanism of this change has not been clarified40.

General Treatment Consideration

Plete remission after 3-6 cycles of chemotherapy received some sort of consolidation therapy in the form of additional chemotherapy, obviating the benefit of radiation. However, such strategies lead to high cumulative doses of chemotherapy and the risk of male infertility due to the use of alkylating agents, cardiomyopathy from anthracyclines, pulmonary fibrosis from bleomy-cin, and of secondary leukemia and lung cancer after alkylating agents and etoposide.

Basic theoretical concepts

In this concept, the initial step is considered dysfunction of the endothelium, the innermost layer of the vasculature, by local disturbances of blood flow, along with metabolic and humoral risk factors (e.g. hyperglycemia, dyslipidemia, cigarette smoking, inflammation). These alterations of the endothelium perpetuate a series of events that culminate in the development of an atherosclerotic plaque.

Dental And Medical Assessments Review of Dental History

The risk for oral and pharyngeal cancer increases with age, tobacco use. frequent use of alcohol, and exposure to sunlight (lip). Oral cancer is treatable if discovered and treated early. Oral and pharyngeal cancer detected at later stages can cause disfigurement, loss of function, decreased quality of life, and death. Surveillance, Epidemiology, and End Results (Sl lik) data indicate that more than 50 of tongue and floor ol mouth cancers had metastasized to a distant site at time of diagnosis.17 In addition, over the last 25 years, the 5-year survival rate of oral cancer has not improved.1 Oral and pharyngeal cancer lesions may not be painful. Oral cancer may appear as an ulceration, a swelling, or a red or white sore that does not heal within 1 to 2 weeks. Other signs of oral cancer may be swollen lymph nodes and difficulty swallowing and speaking.8

Antitumor Sulfonamides

The development of CAIs possessing potent tumor cell growth inhibitory properties was reported by this group (Supuran and Scozzafava 2000b, 2000c Scozzafava and Supuran 2000a Supuran et al. 2001). Such compounds were discovered in a large screening program in collaboration with the National Institutes of Health (NIH) of sulfonamide CAIs. Several hundred aromatic heterocyclic sulfonamides were assessed in vitro as potential inhibitors of growth of a multitude of tumor cell lines, such as leukemia, nonsmall cell lung cancer, ovarian, melanoma, colon, CNS, renal, prostate and breast cancers. The active compounds (most of them nanomolar inhibitors of CA II and CA IV), of types 4.212 to 4.223, belong to both the aromatic and the heterocyclic sulfonamide classes and showed GI50 values (molarity of inhibitor producing a 50 inhibition of tumor cell growth after a 48-h exposure to the drug) in the micromolar range (Supuran and Scozzafava 2000b, 2000c). Better antitumor compounds were then...

Detection Of Second Malignancies Strategies For Screening

Despite the prevalence of lung cancer after lymphoma therapy, there is no clear role for prospective imaging as screening. The role of chest CT as screening is currently being studied in a prospective randomized trial in other high-risk groups,48 but survivors of lymphoma are not included in the study. There are no clear data suggesting a benefit to regular imaging. However, there should be a low threshold to image the chest for any signs or symptoms that could represent a thoracic malignancy. Given the clear increased risk of secondary malignancies in patients who smoke, we recommend counseling against tobacco use.

Stage 2 Contemplation

The short-term and long-term effects of quitting smoking. Short-term advantages are being in better shape and feeling more energetic, having a better skin, better taste and smell, a better voice, and whiter teeth. Long-term effects are a better prognosis, adding years to life, less chance of, or improvement of, lung diseases and heart and vascular diseases, less chance of lung cancer and other forms of cancer. In this stage possible misconceptions must be dispelled. These topics must be discussed to help the patient make a conscious decision.

Solitary Pulmonary Nodule

The solitary pulmonary nodule is defined as a nodule surrounded by normal parenchyma. Approximately 35 of solitary pulmonary nodules are malignant. Proper management of a solitary nodule in an individual patient depends on a variety of elements age, risk factors, presence of calcifications, and size of the nodule. The presence and type of calcification on a solitary pulmonary nodule can be helpful. Popcorn and bull's-eye calcifications suggest a benign process. In low-risk patients (i.e age 35 years and younger and non-smokers), a solitary calcified nodule can be followed every 3 months with 38.31 A 33-year-old woman who is a nonsmoker had lost 30 lb and had a cough. She is noted to have a lung mass on chest radiograph. Which of the following lung cancers is the most likely cell type

Lay Advice and Support

There is a good deal of evidence to support the use of peer mentors (also called lay advisors or buddies) with at-risk patients13 and cardiac patients. For example, peer advisors can provide social support to decrease heart disease-related depression, encourage healthy recovery, and decrease hospital readmission rate.14 Peer support for cardiac surgery patients reduced anxiety and led to increased activity post surgery.15 Peer support groups for people 12 months after a cardiac event led to an increase in physical activity and smoking cessation.16 Home visits to post-Mi patients by trained lay volunteers, who had attended CR themselves, significantly increased the likelihood of attendance at CR. Peer support was also shown to be useful in promoting exercise in seniors,17 and using peers as an extension to care by nurses to post-Mi patients had positive outcomes for both patient and the peer advisor.18

The Role Of Nanotechnology In Drug Delivery

Experimental researches over years have been exploring the possibility and extent of realization of transdermal drug delivery. The first successful model of transdermal delivery was a scopo-lamine patch created in 1979. There have been earlier studies on the barriers to a transdermal delivery dating back to as early as 1924. In the United States, annual expenditure in drug delivery in more than 3 billions, such a high profile industry namely health care is not driven for mere disease and injury therapies but also for novel applications such an nicotine delivery 28 . The consequences of delivery nicotine by patches through skin have led to creation of more than one million smokers who were otherwise 28 .

Ecadherin dependent regulation of cellcell adhesion by EFAs

Expression of E-eadherin by GLA in cancer cells. Tumour cells were treated with either a range of PUFAs (A and B) or with GLA for upto 48 hours (C and D) and then proteins were extracted, separated with SDS-PAGE and molecule visualised with enhanced chemiluminiscence. The relative level of the molecule is indicated in the figure as relative protein band densities from the corresponding gel photo. GLA, among the fatty acids tested, selectively up-regulated the expression of E-cadherin, a 120kDa cell-cell adhesion molecule (A and B). This effect was seen 24 hours after treatment (C and D). A HRT18 human colon cancer cell B and C PLC PRF 5 human liver cancer cell D Cor L23 human lung cancer cells (47). Figure 5. Expression of E-eadherin by GLA in cancer cells. Tumour cells were treated with either a range of PUFAs (A and B) or with GLA for upto 48 hours (C and D) and then proteins were extracted, separated with SDS-PAGE and molecule visualised with enhanced chemiluminiscence....

Both Collagen and Elastin are Affected in Pulmonary Emphysema

In emphysema, major disruptions of the extracellular matrix occurs with a resulting enlargement of the air spaces. For many years, the focus has been on elastin since the most prominent histological change is a loss of elastin fibers particularly at junction points in the alveolar walls (98). Chemically, there are changes in all components of the connective tissue including elastin (99) and the total elastin content of emphysematous lungs is less than for normal lungs (100). It has been assumed that an imbalance between proteolytic enzymes, especially elastase, and proteinase inhibitors such as a-1-antitrypsin results in the loss of elastin fibers (101,102). This assumption is strongly supported by five facts 1 Individuals homozygous for a-1-antitrypsin deficiency often go on to develop emphysema (103). 2 Cigarette smoking, which alters a-1-antitrypsin chemically (104) and which leads to an increase in neutrophil elastase-derived fibrinopeptides in the serum of smokers (105), is a...

Gender Issues in Rehabilitation

Little is known about the needs and experiences of women with regard to cardiac rehabilitation. Diabetes, lipid abnormalities, cigarette smoking, and probably also psychological factors seem to be of special importance. Symptoms and signs of myocardial ischemia and infarction may be different from those in men. Women are less likely to be referred to cardiac rehabilitation programs, are less interested, and have higher drop-out rates than men. Cardiac rehabilitation programs should be made more attractive for women. However, further research in this field is urgently needed.

Autoimmune Diseases

(2) the frequency of p53 AAb is significantly higher in risk groups for lung cancer compared to healthy blood Found in a patient with bladder and metastatic lung cancer 44 Found in patients with HCC, lung cancer and dysgerminoma 56 Therefore, p53 AAb should be determined in larger risk groups (e.g., smokers) for early diagnosis and therapy of cancer. On account of the low frequency, other possible autoimmune tumor markers, e.g., AAb against L-myc, pi85HKR 2 neL1 or some of those described below, should be further evaluated. Sera of cancer patients have been shown to be useful reagents for identifying new cellular proteins possibly involved in tumor development. A new cell-cycle-specific DNA-binding nuclear protein has been identified using autoimmune serum of a patient with bladder and metastatic lung cancer 43, 44 , This serum produced a previously undescribed cell-cycle-related staining pattern on HEp-2 cells. According to the cell-cycle distribution the detected antigen was...

Rehabilitation in Peripheral Vascular Disease

The patient with peripheral artery disease is a potential polyvascular patient. Thus, an integrated approach to prevention and treatment of atherothrombosis as a whole (smoking cessation, aggressive treatment of dyslipidemia, diabetes mellitus, and hypertension) is warranted.

Effects Of Smoking On The Response To Periodontal Therapy

Numerous studies have indicated that current smokers do not respond as well to periodontal therapy as non-smokers or former smokers (Table H ' ). I he majority of clinical research supports the observation that pocket depth reduction is more effective in nonsmokers than in smokers using nonsurgical periodontal therapy (Phase I therapy) including oral hygiene instruction, scaling, and root planing.1 In addition, gains in clinical attachment as a result of scaling and root planing are less pronounced in smokers than in nonsmokers. In a study of patients with previously unhealed advanced periodontal disease, scaling and root planing plus oral hygiene resulted in significantly greater average reductions in pocket depth and bleeding on probing in nonsmokers than in smokers when evaluated 6 months after completion of therapy. Average pocket reductions of 2 S mm tor nonsmokers and 1.9 mm for smokers were observed in pockets that averaged 7 mm before treatment, even though plaque scores were...

Summary and Conclusion

Because of nicotine, smoking is quickly and strongly addictive. This will result in a chronic change in the brain, causing a strong craving and a high chance of relapse after quitting. Greater understanding of the neurophysi-ological background of addiction, that is, the disruption of the neuroreceptors, has increased the possibilities of treatment with medication. Cardiac rehabilitation plays an important role in supporting the patient to quit smoking. Fur

From Cancer Classification To Drug Discovery

The early landmark paper, which unleashed the power of gene expression and microarray technologies, demonstrated accurate classification of hematologic malignancy-acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) 1 . This study demonstrated that molecular signatures could clearly classify patients at the clinic. The study led the way for microarrays to gain importance in several areas tumor classification, prediction of tumor classes, molecular diagnostics, and revelation of the genetic defects, the Achilles' heel of cancers. Subsequently, many solid tumor studies were performed using DNA microarrays. For example, in breast and lung cancer, the focus moved from tumor classification based on unsupervised clustering of gene expression index 2-4 to dissection of solid tumors in the context of patient survival 5 and defining tumors by metastasis signatures from multiple data sets and cancer subtypes 6,7 . These cancer studies were able to reveal gene expression class-based...

Relationship Between Diagnosis And Prognosis

In contrast, although patients with generalized aggressive periodontitis also .ire young patients (usually under age 30), they present with generalized interproximal attachment loss and a poor antibody response to infecting agents (see I'ig. 3-5). Secondary contributing factors such as cigarette smoking are often present. These factors, coupled with the alterations in host defense seen in many of these patients, may result in a case that does not respond well to conventional periodontal therapy (scaling with root planing, oral hygiene instruction, and surgical intervention). Therefore these patients often have a lair, poor, or questionable prognosis, and the use of systemic antibiotics should be considered to help control the disease (see hapter 45).

Chemokines And Gastric Hypochlorhydria

In vitro studies suggest that IL-1 a may act as an autocrine growth factor for gastric cancer cells (58). Although a similar role has been proposed for IL-8 with some tumor cells (93), IL-8 does not appear to be an autocrine growth factor of gastric cancer cell lines (unpublished observations). One area in which elevated chemokines in gastric juice may be relevant to gastric tumorigenesis is their important role in mediating (63,99,102) or inhibiting (102,103) angiogenesis. The C-X-C chemokines with the ELR (Glu-Leu-Arg) sequence have been reported to have angiogenic effects, whereas the non-ELR members of the C-X-C subfamily (e.g., platelet factor 4) inhibit angiogenesis (102,103). The composition of chemokines in hypochlorhydric gastric juice may be important in the regulation of tumor neovascularization and therefore the initiation and maintenance of tumor growth. Local production of IL-8 by gastric cancer cells (28) may also be relevant to angiogenesis and thus metastatic...

Gender Differences in Coronary Heart Disease

Although women and men share several conventional risk factors for CHD, both non-modifiable (age and genetic predisposition) and modifiable (cigarette smoking, hypertension, obesity, dyslipi-demia, diabetes mellitus, sedentary life style, and psychological stress),their impact may be different in women.4 Recently nine major risk factors were found to be responsible for 90 of the myocardial infarctions.5 Diabetes mellitus,lipid abnormalities, cigarette smoking, and possibly also psychosocial factors, seem to be of special importance in women.6 Diabetes mellitus seems to abolish the gender protection in women and is associated with a less favorable in-hospital and long-term prognosis in subjects with MI, with a greater adverse impact for women than for men. Low HDL cholesterol and elevated triglyceride levels may be particularly important in younger women and may better predict CHD in women than total and LDL cholesterol levels. Also the ApoB ApoA1 ratio has been claimed to be of...

Iga And Other Neoplasms

In 96 patients with lung cancer, concentrations of IgG, IgA, IgM, C3 and C4 were evaluated and compared with cell type and controls. Forty-nine patients had squamous cell carcinoma, 11 adenocarcinoma and 20 small cell carcinoma. Sixteen were not defined. IgA and complement were significantly elevated in almost all cancer patients when compared to controls 71 . Rossel et al. 72 evaluated a large group of patients with lung cancer and a corresponding control population, for secretory component and secretory Ig. Since polymeric immunoglobulin receptor is synthesized by bronchial epithelial cells and released into the lumen as secretory component or secretory Ig (slgA, slgM), expression may be up-regulated in patients with lung cancers. Serum secretory component and slgA levels were significantly elevated in patients with cancer and other nonneoplastic diseases when compared to controls. Adenocarcinoma of the lung was associated with the highest levels. T lymphocytes with membrane...

The Era Of Dna Microarrays

FIGURE 9.2 In diseases such as cancer, systems biology-level approaches are needed to understand basic gene regulation (i.e., a list of genes that are classifiers) or, perhaps, to predict class of distinct patient groups. Classification and its accuracy are very important for firstpass diagnosis of the disease in patient populations to better detect, diagnose, and describe the disease these results have an impact on drug response and clinical trials. A tumor may look phenotypically identical by morphometric analysis, but could be very different at the molecular level as has been discovered for many solid tumors like lung cancer 3,4,6,13,14 . As evident from reviewing these studies, alterations in molecular circuitry that are causative of disease, or are markers in cohorts of patients, can also indicate druggable pathways. Sometimes, the pathway changes are not discernible or, perhaps, difficult to use as a target. A recent group has shown the importance of directly moving into marker...

Cardiovascular Risk Factors

The cardiovascular risk profile in elderly patients differs considerably from that in younger patients (Table 47-3). There are fewer smokers but more patients with diabetes and arterial hypertension. The body mass generally decreases with age. The lipid profile shows generally lower triglycerides and a higher HDL cholesterol. Psychosocial risk factors such as hostility, anxiety, and stress are encountered with lower frequency compared to younger patients.1517

Impact Of Mechanismbased Studies In Cancer Drug Discovery And Development

Population statistics and epidemiology. Such efforts are all dependent upon a series of tools, including informatics and platform tools such as sequencing, PCR, and DNA microarrays. In the discovery of cancer drugs such as Herceptin, EGFR inhibitor (Iressa and Tarceva) for lung cancer, and Imitanib (Gleevec) for CML and GIST, it has become common knowledge that a systematic dissection of molecular biology mechanisms is needed to understand the Achilles' heel of cancer and discover drugs that resolve the outcome of patients who suffer from cancers. Many of the findings reviewed here were dependent upon powerful genetic and biochemical approaches or assays. Poor understanding of tumor classes and effective stratification can also affect drug discovery outcomes and is perhaps the case for Iressa 13,14,49,50 . Microarray-based classification therefore has a tremendous role in classifying such cancer patients, as well as in the future of personalized medicine. Even findings from Stegmaier...

Human Diseases Linked to Inherited Defects in DNA Repair Genes

A number of abnormalities in nucleotide excision repair including the syndromes xeroderma pigmentosum, Cockayne syndrome, and tri-chothiodystrophy are associated with abnormalities of organ function and maintenance, skin disorders, sun and radiation hypersensitivity, malignant transformation, and, to a lesser extent, premature aging with the loss of hematopoietic function and bone structure. These syndromes are also associated with premature cancers, both skin and epithelial cancers such as prostate cancer and lung cancer, and leukemias (de Boer

Carotenoids and Radicals Interactions with Other Nutrients

Ascorbic Acid Quench

Furthermore, carotenoid antioxidant activity depends on numerous other factors among which are the concentration and cellular distribution of the substance. Possibly related is that while early epidemiological studies have suggested a link between diets rich in carotenoids and a lower incidence of several serious diseases (9-11), subsequent epidemiological findings suggest little health benefits from dietary supplementation with -carotene. There is even a possible deleterious effect in some subpopulations, such as heavy smokers (12,13). Figure 3 shows the decay of the radical cation of monomer -carotene in unilamellar liposomes (monitored at 920 nm, in the absence and presence of vitamin C). Quenching is clear even though the decay kinetics are somewhat complex. Analysis of the decay curves shows a good fit with two or more exponential decays in the presence of vitamin C and a single exponential decay in its absence. We interpret this as quenching of the -carotene radical cation in...

The Importance of Patient Centred Outcomes

The real value of any cachexia intervention can only be truly measured by assessing the day-to-day impact on the individual patient, whether that be an impact on QoL or patient independence. Over the past 20 years, the importance of such patient-centred outcomes has become evident. Studies have shown that cancer patients receiving palliative care are interested not only in the quantity of their remaining life, but also the quality. For example, in a recent survey of patients with advanced lung cancer, only 22 of patients chose palliative chemotherapy, in preference to supportive care alone, to benefit from the associated 3-month survival advantage 30 . In contrast, 68 of patients chose chemotherapy if it substantially reduced adverse symptoms without prolonging life.

Systemic Inflammation

Over the past two decades, it has become apparent that the presence of systemic inflammation is a significant adverse prognostic factor in a variety of major disease processes, including both atherosclerosis 53 and cancer 54 , the two major causes of mortality in western society. It has been shown in a variety of tumour types (e.g. pancreatic 54 ,gastric 55 , oesophageal 56 , colorectal 57 , non-small cell lung cancer 58 , breast 59 , renal 60 ) that the presence of systemic inflammation is associated with a shortened overall duration of survival. Moreover, the severity of such inflammation also correlates with survival duration 61 . It has been shown in an animal model of cancer cachexia 62 , and to some extent in humans 63-65 , that proinflammatory mediators play a dominant pathophysiological role. Patients with systemic inflammation exhibit an elevated REE

Nontraumatic brachial plexopathy

Nontraumatic brachial plexopathy may have a wide variety of causes, including the following primary or metastatic tumors of neurogenic and other origins inflammatory conditions, such as chronic inflammatory demyelinating polyneurop-athy (CIDP) or brachial neuritis (Parsonage-Turner syndrome) or radiation fibrosis, commonly secondary to treatment for breast or lung cancer. For nontraumatic brachial plexopathy, MRI is the modality of choice for imaging 1,4,27 . The largest published review of brachial plexus imaging found that radiation fibrosis was the most common referral indication for the brachial plexus, but the range of pathology was broad, with breast and lung cancer far outweighing other primary and meta-static tumors, including lymphoma 28 . The current authors recently have witnessed an increase in requests for MRI of the brachial plexus in the evaluation of CIDP and its variants, primarily to localize signal abnormalities in the plexus for the purpose of biopsy and to follow...

The Impetus Behind Studying and Treating the Cancer Anorexia Weight Loss Syndrome

Decline in functional status, as assessed by patient questionnaire data (p 0.004) 4 . In lung cancer patients, Sarna et al. found that weight loss was associated with decreased functional status over a 30-week period 5 . Hence, the primary goals of treating the anorexia weight loss syndrome are to improve both survival and quality of life in patients with advanced, incurable cancer.

Coronary artery bypass grafts in the era of percutaneous coronary angioplasty

This predicted demise of the speciality might be thought as unprecedented in the history of cardiothoracic surgery. They are wrong In the late 1950s, antibiotics and improved housing conditions caused the rapid fall in the requirement for tuberculosis surgery. The surgeons who performed the operations including thoracoplasty, were highly skilled and produced fabulous results for their time. When their services were no longer required, cardiac surgery was evolving and it was anticipated that that these gifted surgeons would just move across and learn a new set of tricks. In fact remarkably few made the transition successfully and those outstanding thoracic surgeons either retired or stuck to lung cancer work.

Endothelial control of coronary vascular tone

Muscle Endothelium Adenosine

Endogenous (for example, arachidonic acid, noradrenaline, thrombin) and pharmacological substances (for example, calcium, nicotine, high potassium), and physicochemical stimuli (shear stress, mechanical stress, hypoxia) can stimulate endothelium-dependent vasoconstriction.15 16 Major endothelium-derived vasoconstrictors are endothelin, thromboxane A2, and prostaglandin H2 (see Fig 4.2) All of the presented data indicate that the endothelial system cannot be viewed as simply an inert lining of blood vessels, but rather it must be regarded as a highly active endocrine organ that serves a wide variety of biological functions including synthesis, metabolism, and binding of various vasoactive and non-vasoactive substances. Impaired endothelial function is likely to contribute significantly to the pathophysiology of coronary artery disease and myocardial ischaemic syndromes. Endothelial dysfunction of the coronary arteries is found across a broad spectrum of conditions in patients free of...

Association With Cell Cycle

Other cyclin dependent kinase inhibitors involving in malignancies include p21 in NSCLC and pancreatic adenocarcinoma, and p15 in leukemia, melanoma and metastatic lung cancer, and p57 in sarcomas and Wilms' tumors. Additional studies are needed in the future will verify their clinical utilities as tumor markers.

Case Study 2 Client X Adidas Employee

Mended by the appropriate national international cardiac rehabilitation organizations (i.e. the European Society of Cardiology Guidelines on Cardiac Rehabilitation and Secondary Prevention), notably exercise conditioning, nutritional dietary counseling, cardiac risk factor management, smoking cessation relapse prevention, stress management, vocational, educational and psychosocial aspects, quality of life measurements specific to cardiac populations, and evaluation outcome measures for the program. In addition, it is highly desirable that a behavioral counseling approach is taken when delivering cardiac rehabilitation wellness preventive services to employees, promoting a client-centered approach towards lifestyle change and cardiovascular risk reduction management.

W Frank Peacock Md Facep

Disproportionately affecting the elderly, HF is the only cardiovascular pathology that is increasing in both incidence and prevalence 1,2 . If under 50 years of age, less than 1 of the U.S. population is diagnosed with HF, but by age 80, this number rises to 10 . This has huge cost implications for our national health system. Inpatient HF costs are estimated as high as 23.1 billion and outpatient costs at 14.7 billion, annually. Annual HF hospitalization costs exceed the combination of costs for breast and lung cancer 3 .

Adenosine 5triphosphate ATP

Cancer cachexia is associated with elevated lipoly-sis, proteolysis, and gluconeogenesis. ATP infusion has been found to significantly inhibit loss of body weight, fat mass, and fat-free mass in patients with advanced lung cancer 196 . Agteresch et al. found that regular infusions of ATP inhibited loss of body weight and improved quality of life in patients with non-small-cell lung cancer (NSCLC)

Syndrome Of Inappropriate Antidiuretic Hormone Secretion Siadh

A variety of tumours, e.g. oat-cell lung cancer, can make vasopressin, and of course they are not subject to normal homeostatic mechanisms. SIADH also occurs in some CNS and respiratory disorders (infection). Dilutional hyponatraemia follows, i.e. low plasma sodium with an inappropriately low plasma osmolality and high urine osmolality. When the plasma sodium approaches 120 mmol 1 treatment should be with fluid restriction ( 500 ml day). Treatment is primarily of the underlying disorder accompanied by fluid restriction. Chemotherapy to the causative tumour or infection is likely to be the most effective treatment. Demeclocycline, which inhibits the renal action of vasopressin, is useful Infusion of isotonic or hypertonic saline must be reserved for extreme emergencies, associated with stupor, and undertaken with great caution. Rapid correction of hyponatraemia must be avoided because of the risk of central pontine myelinolysis the rate of correction must not exceed 12 mmol 1 per 24 h.

Micronutrients Smoking

Cigarette smoke is a powerful oxidant causing widespread cell damage and may accelerate atherosclerosis and other degenerative changes in the skin, lungs, and other organs.6-8 Vitamin E requirements are higher in smokers supplementation may help reduce oxidative damage9,10 Supplements of folate and vitamin B12 can reduce severity of the precancerous changes in the lungs of regular smokers3 Smokers breakdown body stores of vitamin C rapidly.2 May help reduce oxidative damage and loss of respiratory function11 Fig. 5.36 Reduced bronchial metaplasia in smokers supplemented with vitamin B12 and folate. 73 chronic smokers with metaplasia (precancerous cells) in their bronchi were given either 10 mg folate plus 0.5 mg vitamin B12 or placebo for 4 months. Direct cytological comparison at 4 months showed significantly greater reduction of metaplasia in the treated group.

Proteasomal Degradation as a Chemopreventive Target

UBE1L expression is reported as repressed in lung cancer cell lines and some lung cancers, directly implicating UBE1L in lung carcino-genesis (Pitha-Rowe et al. 2004b Kok et al. 1993). Immunoblot expression of UBE1L has been shown to be reduced in some examined malignant as compared to adjacent normal lung tissues (Pitha-Rowe et al. 2004b). In the histologically normal human bronchial epithelium, immunohistochemical analyses revealed abundant UBE1L but low levels of cyclin D1, implicating an inverse relationship between these species (Pitha-Rowe et al. 2004b). A direct relationship between these species was confirmed by co-transfection experiments conducted in HBE cells, where UBE1L was shown to repress cyclin D1 expression in a UBE1L dose-dependent manner (Pitha-Rowe et al. 2004b). This finding mechanistically linked UBE1L to retinoid chemoprevention by conferring repression of cyclin D1 protein expression (Pitha-Rowe et al. 2004b). This has also directly implicated UBE1L as a...

Progestogenonly Contraception

Progestogen-only contraception is particularly appropriate to women having an absolute contraindication for oestrogen, e.g. history of thromboembolism, smokers over 35 years (who refuse to give it up), and for diabetics. Hypertension is not an absolute contraindication to the more effective combined pill since only a proportion of women have oestrogen dependent hypertension (and often such women are normotensive until exposed to increased levels of oestrogen). It is used by lactating women as it interferes with the milk less than the combined pill.

EGFR as a Chemoprevention Target

The described bronchial epithelial chemopre-ventive model has proven useful to highlight the epidermal growth factor receptor (EGFR) as another chemoprevention target (Lonardo et al. 2002). Carcinogen-transformed bronchial epithelial cells, as compared to RA-chemoprevented cells, overexpressed EGFR (Lonardo et al. 2002). EGFR activation promotes cellular growth and transformation and signals other biological effects (Salomon et al. 1995). EGFR overexpression is frequently observed in malignancies, including non-small-cell lung cancer (NSCLC) as well as in premalignant lung lesions (Rusch et al. 1995, 1996). Overexpression of EGFR and its ligand(s) often enhances EGFR-associated tyrosine ki-nase activity and triggers EGFR-dependent effects that regulate tumorigenesis (Salomon et al. 1995). RA is known to repress EGFR expression through a transcriptional mechanism (Lonardo et al. 2002). In bronchial epithelial cells treated with the epidermal growth factor (EGF), RA also prevented...

Define Program Content Table 591

This includes the design of the program, that is, inclusion criteria for participation, description of the different interventions (physical training, psychological support, dietary counseling, smoking cessation, vocational guidance), duration, number of sessions. It should contain a description of the structure of the cardiac rehabilitation staff, facilities (training halls, equipment), and safety precautions. Financial issues should be addressed costs of the program, costs for the participant, resources available from healthcare providers.

Overview Of Genetic Study Designs

Polygenic Model For Periodontitis

The term genetic marker refers to any gene or nucleotide sequence that can be mapped to a specific location or region on a chromosome, from a genetic epidemiologic viewpoint, any marker that is sufficiently polymorphic, or variable, in the population can be used to map or locate disease alleles. Finally, there is an important distinction between the role of genes in monogenic disorders such as Huntington's disease and their role in complex multifactorial diseases such as periodontitis. In monogenic disorders, genes are referred to as causative because nearly everyone with the mutation develops the condition Knvironmcntal factors generally play a minor role in determining the phenotype. In contrast, genes involved in complex multifactorial diseases are often referred to as susceptibility genes (or more correctly, susceptibility alleles), l or these diseases, individuals who inherit susceptibility alleles will not develop disease unless they are exposed to deleterious environments. Tor...

Decision Theory Modeling Cost Effectiveness

Ades and colleagues carried out a decision theory modeling exercise of the cost-effectiveness of CR after myocardial infarction (MI) using the perspective of the patient or insurance payer.19 In this model they used the total of direct medical expenditures (less costs associated with drugs, outpatient care and home care) including cost data derived from 626 operating CR centers minus the direct savings realized from averted medical care. Health outcome data were derived from published results of RCTs on mortality and epidemiological studies of long-term survival. An incremental life expectancy of 0.202 years during a 15-year period following rehabilitation was estimated and, with inflation-adjusted costs in 1995 US , the ICER for CR was estimated as 4950 LYS (Table 60-1). The authors conclude by stating that CR is more cost-effective than thrombolytic therapy, coronary bypass surgery, and cholesterol lowering drugs, though less cost-effective than smoking cessation and should stand...

Definition Of Prognosis

Prognosis is often confused with the term risk. Risk generally deals with the likelihood that an individual will get a disease in a specified period (see Chapter S). Risk factors are those characteristics of an individual that put them at increased risk lor getting a disease. In contrast, prognosis is the prediction of the course or outcome of a disease. Prognostic factors are characteristics that predict the outcome of disease once the disease is present. In some cases, risk factors and prognostic factors are the same (see Chapter 5). lor example, patients with diabetes or patients who smoke are more at risk for acquiring periodontal disease, and once they have it, they generallv have a worse prognosis.

Comparing the performance of selfassessment questionnaires

Several studies (19-22) have compared the performance characteristics of the various indices. Cadarette and colleagues (19) compared the performance of the ORAI index to that of SCORE, ABONE, the 1998 NOF guidelines22 and the body weight criterion in a population of 2365 postmenopausal women age 45 and older who were participating in the CaMos study. These women were otherwise healthy women who had not taken HRT or any other bone-sparing agent or who had taken HRT for 5 years or more. The average age was 66.4 years and the average weight was 152 lb (69 kg). Bone density was measured at the femoral neck and T-scores were calculated using the manufacturer's reference data for Canadian women in which the mean and SD were 0.857 g cm2 and 0.125 g cm2, respectively.23 To compare the performance of the 1998 NOF guidelines to the risk indices, the authors converted the NOF guidelines to an index scoring system in which 1 point was awarded for age 65 or older, weight less than 127 lb (57.6...

Significance of p53 Gene Mutation

A specific sensitivity to chemotherapeutic agents has been reported for certain mutations (28). Even if the different types of mutations as well as the different location of mutations confer a specific grade of treatment sensitivity, clinically this does not seem to impair the prognostic and predictive implications of p53. While the response to (p53-dependent) treatment was shown to be related to the p53 genotype in more than 168 patients from neoadjuvant studies, we were unable to identify a single tumor that responded to treatment in the presence of a p53 mutation (Table 2 6-8 ). This was found to be true for more than 70 different mutations in thep53 gene. The results were reproducible in three different tumor types (breast, colorectal, lung cancer).

Differential Response Of Breast Carcinoma To Epidermal Growth Factor Receptor Inhibitors

Until recently, the molecular mechanisms underlying the sensitivity of tyrosine kinase inhibitors remained unknown. Paradoxical associations between EGFR expression and response to treatment lead to further confusion regarding determinants of response to therapy. Recently demonstrated in nonsmall cell lung cancer was the observation that specific mutations in the EGFR tyrosine kinase domain predicted for response to treatment with agents that block EGFR receptors. Two separate study groups (98,99) reported the discovery and the identification of missense and deletion mutations that cause the EGFR to have a much higher affinity for gefitinib and hence lead to an increased responsiveness to the tyrosine kinase inhibitor. Recently reported were the results of Lee et al. (100) who investigated the presence of somatic mutations of ErbB2 kinase domain in gastric, colorectal, and breast carcinomas. The authors concluded that in addition to lung adeno-carcinomas, ErbB2 kinase domain mutations...

The Snp Chip Flowthrough Methods

Metrigenix (Baltimore, MD, www.metrigenix.com, Figure 19.2LL) utilizes a patented flow-through chip technology (FTC) that serves as the technology base for the MetriGenix microarray 51 . The FTC is a state-of-the-art three-dimensional microarray technology platform that can be used to provide high-throughput, high-content assays to measure gene expression or genetic polymorphisms. The flexibility of the system is based on the detection biomolecules bound to the chip surface, but the speed of hybridization exceeds standard surface hybridization techniques by several orders of magnitude due to molecular availability. The applications to date include colon cancer biomarker detection, as well as nonsmall cell lung cancer signatures.

A passion for complexity and the challenge of longterm research

Alsana well it's very difficult to pinpoint a specific risk factor it's not like lung cancer where 99 per cent is a result of smoking. It's not as clear cut as that and I don't think it ever will be. I don't think it's ever going to be one specific factor per se. It's not only the fact that you can get tumours in various different organs but the fact that each organ can have tumours of different types. This is what makes it fascinating. I think there are going to be many things that interact with each other. I don't know whether it's pollution whether it's diet or hormone changes related to lifestyle. I suppose they all or the majority of them contribute in some way.

Treatment of Graves Disease

When managing the problems of active Graves' disease, the following measures are known to be of benefit maintenance of a euthyroid state, avoidance of cigarette smoking (very important), use of topical hydrating agents (with or without preservatives, as needed), and nonsteroidal anti-inflammatory drugs. These are largely supportive therapy, allowing time to pass and inflammatory activity to subside, while protecting vision in the meantime. This is adequate for a majority of cases. Infrequently, one encounters cases of fulminant inflammatory disease that threaten destruction of the eye through extreme exposure of the ocular surface and formation of corneal ulcers, or by compression of the optic nerve, which can destroy vision to the point of no light perception. The use of orbital irradiation and or surgical decompression should be saved for these very dangerous, high-risk cases. High doses of oral corticosteroids, such as 1 mg kg of body weight of prednisone, can be used

Clinical Implications Of Genetic Studies

The Identification ol genetic risk factors lor periodontitis in no way mitigates the importance of recognizing and controlling important environmental risk factors. For example, tobacco use is a major risk factor in AT. The risk of disease attributed to smoking appears to override any genetic susceptibility or resistance to disease.' Par patients who smoke, preventive strategies must address the overwhelming environmental factor tobacco use. It also is possible that new treatment strategies will be developed to directly counter the deleterious effects of certain risk allele si simple theoretic example is the use of select antiinflammatory drugs in patients who tire genetically programmed to be hvperresponders to bacterial antigens.

Toxic Optic Neuropathies Definition

Ethambutol and other antitubercular drugs, cytostatic agents, heavy metals, hexachlorophene, and methanol can all cause a toxic optic neuropathy (also see Chap. 17). The first priority is to identify the offending agent and then to block further exposure. Specific measures that follow are determined by the nature of the toxin. The most common syndrome of toxic damage to the optic nerve chiasm is that of tobacco-alcohol amblyopia. It is thought that the toxin in question is cyanide, which is present in trace quantities in tobacco smoke. Interventional therapy with oral multivitamins (e.g., vitamin B complex) and intramuscular injections of hydroxycobalamine (the decyanated form of vitamin B12) can reverse the visual loss in the early stages of the disease. These vitamins are thought to chelate trace levels of cyanide and detoxify the affected tissues. Some individuals may be more at risk than others are, based on the composition of their mitochondrial DNA and variations in the...

Comprehension Questions

17.2 A 48-year-old male presents for follow-up of an elevated calcium level of 12.3 mg dL found on routine screening labs at his last well-male visit. He takes no medications other than an occasional antihistamine for allergies. He recently started smoking a half-pack of cigarettes per day. He was prompted to attend to his well-male visit by his wife who claims that he has become forgetful, has a decreased appetite, and has had a 10-pound weight loss over the past 2 months. As part of his follow-up labs, you obtain a serum PTH. which comes back within the normal range. What is the next step in diagnosis 17.3 You obtain follow-up labs for a hypercalcemic patient and find that the PTH level is suppressed. There tire no suspect medications. You suspect lung cancer based on a 30 pack-year smoking history, but the chest x-ray is normal. What do you do next

Antihypertensive Drugs

Blood pressure lowering therapy should be considered in individuals with repeated measures of systolic blood pressure 140mmHg and or diastolic blood pressure 90mmHg. Guidelines recommend that the overall cardiovascular risk should be considered.1 Treatment directed at lowering blood pressure should include lifestyle change encompassing smoking cessation, moderation of alcohol consumption, weight reduction, physical exercise, reduction of high salt intake and other dietary changes. When these measures fail, pharmacological treatment is indicated.

Prevention Guidelines Management of the Coronary Patient

Regarding smoking of tobacco, results from EUROASPIRE7,8 have shown that 1 in 4 to 1 in 5 of our patients continue to smoke after an acute event. They should be encouraged by health professionals to permanently stop smoking all forms of tobacco. The momentum for smoking cessation is particularly strong at the time of an acute event, an invasive treatment, or vascular surgery. However, relapse occurs frequently. Therefore this problem should be identified at all possible occasions.

Factors Involved In The Prooxidant Activity Of Carotenoids

Once produced, the fate of such carotenoid radicals is of interest. The carotenoid radical cation (CAR'+) itself is unreactive and decays slowly by second-order kinetics to unknown products, which do not significantly interact with oxygen and which do not continue the chain reaction, as suggested by Truscott (14). However, since such a radical is rather long lived, it could migrate to a site where damaging consequences arise unless a mechanism is available for its removal (14). A recent finding suggests that it can be efficiently repaired by cell antioxidants, such as vitamin C. On the other hand, the carotene radicals (CAR' and ROO-CAR') may act as pro-oxidants and undergo oxidation, especially under elevated oxygen partial pressures (16). While at low po2, the CAR'+ is mainly formed and carotenoids act as chain-breaking antioxidants, consuming peroxyl radicals (8,17), whereas at high po2, the carotenoid radicals are hypothesized to react with oxygen to produce carotenoid peroxyl...

Future Developments in Preventive Cardiology The Euroaction Project

Cardiac rehabilitation traditionally focused on physical rehabilitation but this specialty has gradually evolved into more comprehensive professional lifestyle programs - smoking cessation, making healthy food choices, and becoming physically active - based on behavioral models of change. Risk factor management in terms of controlling blood pressure, lipids and glucose to defined targets, and the use of prophylactic drug therapies, is also now an integral part of this approach. Finally, the psychosocial and vocational support required to help patients lead as full a life as possible is also provided. This evolution in

Physical Examination Multiple Choice

An 83-year-old woman presents to the ER the afternoon of Thanksgiving complaining of severe abdominal pain. She states it was at first cramping around her navel but has now radiated to the rest of her abdomen. She also complains of some vomiting and bloody diarrhea. About 1 hour before the pain started, she had a large traditional holiday meal. She states she generally only eats about half a sandwich and some soup at meals. She denies any earlier history of similar pain. Her past medical history is significant for coronary artery disease, for which she has had a stent placed in the past. She is only taking medicines related to her heart condition. She denies any alcohol, drug, or tobacco use. Her review of systems is positive for soreness in her legs while walking and occasional chest pain on exertion. On exam, you find an elderly woman in great distress. She is pale and tachycardic. Examining her abdomen, you hear decreased bowel sounds. On palpitation, her abdomen is rigid with...

Inflammatory Biomarkers and Clinical Utility

A more optimistic position would argue that residual risk indicated by inflammatory biomarkers in an optimally managed patient could provide impetus for intensification of lifestyle measures to ameliorate the individual's inflammatory profile. Weight loss, dietary interventions, smoking cessation, and regular physical activity may all mitigate inflammation beyond pharmacotherapy. Statins have received the greatest attention as pharmacological modifiers of inflammatory biomarkers. However, increasing evidence supports the possibility that other classes of medications may likewise modulate inflammation. Although aspirin has not consistently reduced levels of CRP, emerging evidence suggests that fibric acid derivatives, thiazolidinediones, and metformin can reduce such levels. The fibric acid derivatives can limit inflammation by activating peroxisome proliferator activated receptor-a (PPAR-a). The thiazolidinediones (e.g., the glitazone class of insulin...

Animal Studies On Pufas And Cancer Metastasis

CLA has been demonstrated to inhibit proliferation of a number of human malignant tumour cells including melanoma, colorectal, breast and lung cancer cell lines. In animals, CLA reduced the incidence of epidermal tumours and forestomach neoplasia in mouse, aberrant crypt foci in rats colon and also mammary tumorigenesis. Further study has demonstrated an effect of CLA on prostate tumour (113). SCID mice were fed with either a standard diet, diets supplemented with 1 linoleic acid (LA) or 1 CLA for 2 weeks prior to subcutaneous (s.c.) inoculation of DU-145 cells. Mice receiving LA-supplemented diet displayed significantly higher body weight, lower food intake and increased local tumour load as compared to the other two groups. Mice fed the CLA-supplemented diet displayed not only smaller local tumours, but also a drastic reduction in lung metastases.

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A Disquistion On The Evils Of Using Tobacco

A Disquistion On The Evils Of Using Tobacco

Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.

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