The Painless Stop Smoking Cure

Quit Smoking Magic

Quit Smoking Magic is the first and Only program of its type that literally can Force You to easily kick the habit in just days even if you have a shoestring budget and absolutely no will power. Benefits: Helps You to successfully quit smoking in as little as just days. Its as easy as taking candy from a Sleeping baby. This system takes just minutes to administer. This system can be done on a shoestring budget. Absolutely no chance of Any negative side effects. Works for almost Everyone 98% success rate thus far. You will never relapse with this program. Theres no Will-power necessary with Quit Smoking Magic. Powerful concept based on Real-life experiences rather than just theories. Quit Smoking Magic Teaches You: How to quit smoking cigarettes super-fast. How to stop your Cravings dead in their tracks. How to Never relapse with this nasty habit. How to avoid spending a ton of Money in your quest for quitting. How to quit smoking Now rather than later. How to Automatically kick this habit even without will-power. How to keep from having withdrawal symptoms and nasty mood swings. How to refrain from having Insomnia after quitting. How to avoid restlessness as well as changes in appetite. More here...

Quit Smoking Magic Overview


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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...

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...

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...

The Role of Tobacco Dependence and Addiction

In successful counseling of coronary patients on quitting smoking, physicians as well as other cardiac rehabilitation team members need to understand the role of dependence on and addiction to nicotine. This complex mechanism and the highly individual combination of contributing factors implies a diagnostic and therapeutic challenge. The aim of this chapter is to give insight into the theoretical background of nicotine addiction and thus provide a basis for smoking cessation as part of a cardiac rehabilitation program.

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...

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 .

Wnt Signaling in Stem Cells and Lung Cancer

Wnt Lung Cancer

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

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...

Nicotine Pharmacodynamics

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...

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.

Cigarette Smoking

As noted above, epidemiologists have attributed as many as 30 of all cancer deaths to tobacco use, primarily cigarette smoking. In 2005, for example, approximately 163,000 deaths due to lung cancer were expected to occur in the United States (90,000 men and 73,000 women), making up about 31 of all deaths from cancer in men and 27 in women.3 Although the most direct correlation is between cigarette smoking and lung cancer, tobacco use has also been implicated in cancers of the mouth, pharynx, larynx, esophagus, urinary bladder, pancreas, kidney, and, more recently, stomach and liver49 and perhaps colorectal cancer.52 Smoking of pipes or cigars has been implicated in the occurrence of cancers of the mouth, pharynx, larynx, and esophagus, but this form of tobacco use is generally considered much less dangerous because the smoke is usually not inhaled. A number of studies have also suggested a correlation between ''passive

Smoking Cessation

Smoking cessation has immediate positive consequences not only in younger, but also in elderly patients. Smoking cessation after aortocoronary bypass surgery in patients over 65 years of age decreases the mortality within a year after surgery by approximately 40 .24 Smoking leads to an immediate increase in blood pressure, peripheral vascular resistance and heart rate and leads to a decrease in flow-mediated vasodilatation of the arteries with concomitant increase in clotting tendency and a decrease in HDL cholesterol.25 This indicates that elderly smokers should be encouraged to stop smoking as is done in younger patients and they should also be offered nicotine replacement medications for suppression of craving if necessary. This recommendation is appropriate up to the age of 75-80 years in old-old patients smoking cessation counseling becomes somewhat questionable, especially if patients are socially isolated after the loss of their friends and if they have the feeling that smoking...

Variability in Micronutrient Requirements among Individuals

Moreover, besides these genetic differences, nutritional requirements can be profoundly influenced by many factors, including age, environment, and lifestyle choices. A smoker's requirement for vitamin C is two to three times that of a nonsmoker.30 Pregnancy doubles a woman's need for iron. Strenuous athletic training sharply increases requirements for the vitamin B complex and magne-sium.31 Therefore, across the population, there a broad range of optimum intakes for the essential nutrients. Factors which cause nutritional needs to vary from person to person are shown in the table below and are considered in detail in later sections.

Transcription Factors as Oncogenes

C-myc is also found to be amplified in pro-leukemia and small cell lung cancer. The c-myc protein requires dimerization with Max to initiate transcription, and Max homodimers serve as an antagonist of transcription. The formation of Mad-Max dimers also suppresses transcription. It is also interesting to note that the full oncogenic potential of c-myc relies on cooperation with other on-cogenes like ras.

Prevention Strategies

Icals in tobacco smoke, automobile exhaust) throughout their lifetimes, cancer preventive agents that work after initiating events have occurred are desirable. Two strategies of decreasing cell proliferation are induction of apoptosis, or cell death, and differentiation, which may or may not be associated with apo-ptosis. Induction of either differentiation or apoptosis will stabilize or decrease, respectively, overall cell number in a tissue.

Age And Carcinogenesis

The incidence of common cancers increases with age (Figure 1). This association is universal 2 and is observed with the aging of any population around the world. A clear explanation of this phenomenon is the time-length of carcinogenesis, a stepwise process involving the activation of cellular oncogenes, and the suppression of anti-proliferative genes (anti-oncogenes)3. It is reasonable to assume that the duration of carcinogenesis reflects the number of stages involved in the pathogenesis of different tumors, and that this number be highest for tumors whose incidence peaks late in life, such as adenocarcinoma of the prostate and of the large bowel, or non-melanomatous skin cancer 3. In the era of chemoprevention and recognition and elimination of environmental carcinogens, an alternative possibility should be considered. These interventions may cause the prolongation of one or more carcinogenic steps and, in so doing they may delay the development of cancer. For example, the...

Targeting Loss of Tumor Suppressor Function and Oncogene Overexpression

Inhibition of cancer cell invasion after overexpression of TIMPs using different gene delivery vectors has been shown in vitro in gastric cancer cells and mammary carcinoma cells (156,157). Overexpression in vitro of TIMP-2, which was delivered by a recombinant ade io-virus (AdTIMP-2), inhibited the invasion of both tumor and endothelial cells in models without affecting cell proliferation (158). Its in vivo efficiency has been evaluated in the LLC murine lung cancer model, the colon cancer C51 model, as well as in MDA-human breast cancer in athymic mice. Preinfection of tumor cells by AdTIMP-2 resulted in an inhibition of tumor establishment in more than 50 of mice in LLC and C51 models and in 100 of mice in the MDA-MB231 model. A single local injection of AdTIMP-2 into preestablished tumors of these three tumor types reduced tumor growth rates by 60-80 , and the tumor-associated angiogenesis index by 25-75 . Lung metastasis of LLC tumors was inhibited by > 90 . In...

Benefits of Cardiac Rehabilitation

Cigarette smoking, improvement in psychosocial well-being and reduction of stress, and reduction in mortality. These are addressed in turn. Appropriately prescribed and conducted exercise training is an integral component of cardiac rehabilitation, particularly for patients with decreased exercise tolerance. Specific activity recommendations are available for women, for older adults, for patients with chronic heart failure and after cardiac transplantation, for stroke survivors, and for patients with claudication as a reflection of peripheral arterial disease. Strength training can improve skeletal muscle strength and endurance. Smoking cessation can be achieved by specific strategies. Lipid management requires intensive nutrition education, counseling, and behavioral interventions to improve dietary fat and cholesterol intake. Optimal lipid control typically entails pharmacologic management, in addition to diet and exercise training. Diet and exercise are recommended for weight...

Use in Prevention and Therapy

Vitamin A is one of nature's primary anticancer substances, particularly in the skin and mucous membranes. Ample intakes of vitamin A have been shown to protect against cancers of the lung, bladder, prostate, larynx, esophagus, stomach, and colon. Vitamin A can prevent precancerous lesions, such as oral leukoplakia (white patches on the lips and mouth often found in smokers) and cervical dysplasia, from developing and may produce regression and disappearance of these disorders.15 As a cancer treatment, large doses of retinoic acid may reduce growth and recurrence of certain forms of skin cancer.16 As an antioxidant, beta-carotene helps provide protection against damage from many xenobiotics (such as polychlorinated biphenyls PCBs ). It may also reduce the risk of skin cancer associated with exposure to sunlight6 and radiation.2 pulmonary disease and asthma, particularly in regular smokers.17

Common Types Of Cancer

In 2003 more than 2 million new cancer cases were diagnosed in the United States alone, and in that same year, more than half a million Americans died of cancer. Cancer can strike anyone, but the risk increases with age, certain lifestyles, and the quality of the environment. Nearly 80 percent of all cancers are diagnosed in patients age 55 and older, and smokers are 20 times more likely to develop lung cancer than nonsmokers. Cancers can appear in any of our tissues and organs, but there are some tissues that are more susceptible than others Skin cells and the epithelial cells lining the lungs and digestive tract are prominent members in this group. All of these tissues and organs are at the interphase between the external environment and our internal organs, and like a sailor on the mast, take the full force of the storm when it hits (see table on page 3). The deadliness of a cancer varies depending on the tissue that is affected. Prostate cancer struck more than 200,000 American...

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

Both 5-fluorouracil and cytosine arabinoside remain widely used in combination cancer chemotherapy. 5-Fluorouracil is one of the most effective drugs against colon cancer (311).Cytosine arabinoside is effective in leu-kemias and lymphomas but has a very short half-life (ca. 12 min in man), because of catab-olism by cytidine deaminase (321), and various non-specific prodrug forms are used (322). Gemcitabine was shown in phase I trials to be active in a number of cancers, especially in non-small-cell lung cancer, where it showed > 20 responses as a single agent and up to 54 in combination with cisplatin (323). In phase II trials, it has proved active in a wide range of tumors, including non-small-cell lung cancer (> 60 responses in combination with cisplatin) (324), urothelial (22-28 responses as monotherapy, 42-66 in combination with

Malignancies Occurring During

Case reports suggest that the development of the two diseases is not coincidental and that scleroderma patients have twice the risk of developing malignancies than the general population. Lung and perhaps breast cancers seem to be more frequent in PSS patients. In a Danish series of 344 patients 7 , scleroderma was responsible for a 3-fold increased risk of death (Table 1). Most patients died of PSS-related causes (acute renal crisis, hypertension, lung fibrosis, etc.), but malignancies were also described. Lung cancer was the most frequent cause of death-related malignancies (13 160 deaths). Hematological malignancies were the second most common cause of death in the cancer group (4 cases). The other causes were anecdotal breast and ovarian cancer (3 of each), uterus, ovarian etc. An over-representation of lymphoma has been suggested by others 8 who observed 2 cases of non-Hodgkin's lymphoma in PSS patients. These authors reported that the standardized incidence ratio for all cancers...

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.

Overview of Carotenoid Function in the Skin

When increasing the amount of carotenoids in the diet or consuming carotenoid-enriched supplements, these nutrients are initially accumulated in the lipoproteins in blood (78). The concentrations can be easily increased by 100 and higher. This increase in blood carotenoids then leads to an increase of carotenoid concentrations in all organs taking up lipoproteins, including skin. It has been shown that skin carotenoid levels are strongly and significantly correlated with carotenoid levels in plasma (66). As is found in plasma, dermal carotenoid levels are lower in smokers than in nonsmokers. -Carotene levels in skin are known to increase with supplementation (79), and supplemental -carotene is used to treat patients with erythropoietic protoporphyria, a photosensitive disorder (80). Supplemental carotenoids have also been shown to delay erythema in normal healthy subjects exposed to UV light (81-83). There is limited evidence that they may be protective against skin malignancies (67),...

Pss And Lung Carcinoma

Further case-reports 3-7 described a similar association between PSS and lung cancer, usually diagnosed in patients known to have had diffused scleroderma involving the lungs for many years prior to the appearance of the malignancy. . The most common type of lung cancer reported in connection with PSS is bronchiolar (alveolar-cell) carcinoma 2-4, 9 (representing less than 4 of all forms of lung cancer). This type of cancer can be found in areas of chronic fibrosis and has been described in association with scarring.

Vincristine Oncovin Vincasar PFS

4.2.3 Vinorelbine (Navelbine) Medicinal Uses. Vinorelbine (37) is used against non-small-cell lung cancer and Things to Come. Vindisine (36) is an analog prepared from vinblastine (34).Its antitumor spectrum, however, is more closely similar to that of vincristine. Clinical studies show activity against acute leukemia lung cancer breast carcinoma squamous cell carcinoma cf the esophagous, head, and neck Hodgkin's disease and non-Hodgkin's lymphomas. Its toxicities include myelosuppression and neurotoxicity. Despite these promising findings, it has yet to be introduced into the clinic (356).

Scientific Foundations

Anticancer drugs interfere with the growth of tumor cells, eventually causing their death. Common chemotherapy drugs used in various cancers include doxorubicin (Adriamycin) in breast cancer, often administered with cyclophosphamide (Cytoxan) paclitaxel (Taxol) in lung cancer and fluorouracil (5-FU) in colon cancer. Some are given only as injections. Others, such as imatinib (Gleevec) for leukemia are taken by mouth in tablet or liquid form.

Noninflammatory Vasculopathies

Thromboangiitis obliterans occurs chiefly in middle-aged men who smoke heavily. It commonly involves the peripheral arteries. The disease may also involve the medium-sized and small meningeal and cerebral arteries, producing intimal proliferation, luminal obliteration, and multiple small infarctions (Fig. 4.30).

Impact Of Imaging Diagnostics On Cancer In Relation With Tumor Markers

In the case of lung cancer, early detection is needed to improve prognosis because most cancers are metastasized when first detected by biomarkers or by cytological assessment of sputum. Mass screening for lung cancer with low-dose X-ray spiral computerized tomography (CT) in mobile units was performed on 5483 individuals from the general population in Japan (13). The detection rate with CT was 0.48 , including cancers of less then 10 mm in diameter, whereas that of standard mass screenings done previously in the same area were 0.03-0.05 , 10 times less sensitive. This high-resolution CT also constitutes an excellent tool for confirmatory discrimination of subtypes of small peripheral lung peripheral adeno-carcinomas (71). Magnetic resonance imaging (MRI) on preoperative local staging of patients with pancreatic cancer was applied to discriminate resectability. MRI results showed 98 sensitivity, 92 specificity, and 96 accuracy in patients with suspected pancreatic tumor (72)....

Chronic Obstructive Pulmonary Disease

In COPD patients, the prevalence of anorexia is particularly high, since most patients suffer from breathlessness, which affects food intake. Recent data indicate that 67 of chronic lung disease patients experience anorexia during the last year of life. This figure is not much different from the prevalence of 76 found among lung cancer patients 12 . More striking, however, are data showing that although COPD patients have physical and psychosocial needs at least as severe as those of lung cancer patients, their symptoms, including anorexia, receive much less attention from health care professionals 12 .

Etiology and Pathogenesis 361 etiology

Besides intense sun exposure, exposure to other environmental carcinogens begins or intensifies during this age period tobacco use, recreational drug use, alcohol use, and sexually transmitted disease. It is unlikely, however, that cancers resulting from these exposures occur during young adulthood. They are much more likely to occur later in life.

Genetic Predisposition and Genetic Susceptibility

In middle to late adult life, cancer occurs as a result of multiple, serially accumulated, genetic changes following decades of exposure to carcinogens like, for example, tobacco smoke. The occurrence of cancer at young ages, when the opportunity for such chronic environmental exposures has not had sufficient time to exist, suggests strongly that individuals are genetically predisposed to develop certain cancers or are genetically susceptible to the carcinogenic effects of environmental agents. In such individuals, the number of genetic changes required to achieve malignant transformation at the cellular level may be reduced and or metabolic processes modified. In many instances, gene-environment interactions in this age range are more likely to be operative.

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...

Validity of Tests for Carcinogenicity

For many years, the prevailing view among cancer epidemiologists has been that 60 to 90 of human cancers are attributable to environmental and lifestyle factors, including cigarette smoking, diet, ultraviolet irradiation, sexual practices, parasitic and viral infections, industrial pollution, and, more recently, pesticides.94,95 event. The no-threshold risk calculation is derived from the extrapolation of high-dose exposure situations. For example, the incidence of lung cancer in deep mineworkers exposed to radon is plotted versus radon exposure linearly back through 0 0 on the plot (Fig. 2-10). In other words, some infinitismal exposure to radon will still cause some cancers. From this sort of extrapolation, it is concluded that no level of exposure to radon is safe. This model is still the one most commonly used for cancer risk assessment by government agencies and its use has led to the propagation of a number of ''cancer myths'' (see Chapter 3).

Starting and stopping use

Contrary to popular belief it is not generally difficult to stop, only 14 finding it 'very difficult'. But ex-smoker status is unstable and the long-term success rate of a smoking withdrawal clinic is rarely above 30 . The situation is summed up by the witticism, 'Giving up smoking is easy, I've done it many times'. Aids to giving up. The addictive effects of tobacco smoking are substantially due to nicotine, and it is logical to substitute nicotine for tobacco smoke as a pharmacological aid to quitting. Nicotine is available in a number of formulations, including chewing gum, transdermal patch, oral and nasal spray. When used casually without special attention to technique, nicotine formulations have proved no better than other aids but, if used carefully and withdrawn as recommended, the accumulated results are almost two times better than in smokers who try to stop without this assistance.19 Restlessness during terminal illness may be due to nicotine withdrawal and go unrecognised...

Passive involuntary smoking

Many nonsmokers are exposed to tobacco smoke, and environmental tobacco smoke has been classified as a known human carcinogen in the USA since 1992.20 Although the risks are, naturally, smaller, the number of people affected is large. One study estimated that breathing other people's smoke increases a person's risk of ischaemic heart disease by a quarter.21 Smoke drawn through the tobacco and taken in by the smoker is known as mainstream smoke. Smoke which arises from smouldering tobacco and passes directly into the surrounding air, whence it may be inhaled by smokers and nonsmokers alike, is known as sidestream smoke. Mainstream and sidestream smoke differ in composition, partly because of the different temperatures at which they are produced. Substances found in greater concentrations in undiluted sidestream smoke than in undiluted mainstream smoke include nicotine (x 2.7), carbon monoxide (x 2.5), ammonia (x 73), 21 Law M R, Morris J K, Wald N J 1997 Environmental tobacco smoke...

Guide To Further Reading

Journal 313 211-215 Mendelson J H, Mello N K Management of cocaine abuse and dependence. New England Journal of Medicine 334 965-972 Ness R B et al Cocaine and tobacco use and the risk of spontaneous abortion. New England Journal of Medicine 340 333-339 Nutt D J 1996 Addiction brain mechanisms and their treatment implications. Lancet 457 31 (see also other articles in this series on pages 97,162, 237, 301,373) Raw M, McNeill A, West R1999 Smoking cessation evidence based recommendations for the healthcare system. British Medical Journal 318 182-185

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

Chemoattractant For Monocytes

Lung cancer cell line (Calu-3) (87) The identification and cloning of MCP-1 provided an opportunity to screen tumors for their expression of a bona fide monocyte-specific chemoattractant. Table 1 lists several types of cell lines, tumor explants, and primary tumor tissues that express MCP-1. Although the list appears to be extensive, MCP-1 expression is not a universal property of tumor cells since there are many tumor types that do not express MCP-1, e.g., prostate carcinoma and many lung cancers (44).

Central Neural Mediation of Cytokine Induced Anorexia

The major hypothalamic detection site for blood-derived signals. Yet, severing the ARC from PVN or its connections with the PVN only slightly attenuated peripheral IL-1p-induced anorexia 35 , indicating that the ARC is involved but not necessary for peripheral IL-1p-induced anorexia. Several lines of evidence 20 implicate activation of hindbrain to forebrain aminergic neurons in the feeding suppression and hypermetabolic effects of circulating IL-1p. IL-1p-induced anorexia may in part be mediated through prostaglandin E2-dependent activation of serotoninergic neurons originating in the raphe nuclei and projecting to the hypothalamus 36 . In line with this idea, systemic administration of a serotonin (5-HT2c) receptor antagonist and microinjection of the 5-HT1A autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) directly into the raphe nucleus both markedly attenuated the feeding-suppressive effect of peripherally injected IL-1-p 3 . Interestingly, anorexia induced...

Mechanisms Of Mcp1 Antitumor Effects

An alternative approach to using MCP-1 was demonstrated by transfecting an MCP-1 cDNA into small-cell lung cancer cell lines that express P-glycoprotein (72). As in other systems, MCP-1 did not alter the growth rate of these cells in vitro, but in this model, MCP-1 expressers formed tumors in nude mice with the same efficiency and growth rate as control cells. However, the tumor-suppressive effects of systemi-cally administered anti-P-glycoprotein antibody were much greater against the MCP-1-expressing cells. This suggests that even when MCP-1-mediated macrophage attraction is insufficient to produce tumor cell death, the presence of MCP-1 can enhance antibody-dependent cellular cytotoxicity. (The MCP-1 effect is probably related to macrophage elicitation in vivo since the addition of recombinant MCP-1 to mixed macrophage tumor cell cultures in vitro did not enhance cytotoxicity.)

Therapeutic interventions

Conclusive evidence that lowering hsCRP levels leads to a reduction in clinical cardiovascular events in primary prevention settings is not available. Nevertheless, many behavioral and pharmacological interventions that reduce cardiovascular event rates are associated with lower hsCRP levels. Behavioral interventions in this category include smoking cessation, weight loss, increased physical activity, and dietary modification (see ref. 6 for a review). Pharmacological interventions are reviewed in the following sections. Because a patient's compliance with recommended interventions depends in part on his or her perception of absolute disease risk and because the addition of hsCRP testing to existing risk algorithms provides an improved prediction tool, a major rationale for hsCRP screening is to help motivate at-risk individuals to adopt healthier lifestyles and to comply with prescribed drug therapies.

Calmodulin and Cell Proliferation

Some investigators have examined the levels of CaM expression in relation to growth responses. Exaggerated growth responses have been recorded in cardiomyo-cytes resulting from an overexpression of CaM (Gruver et al. 1993). Recently, however, Prostko et al. (1997) found no effects on growth responses arising from an overexpression of CaM in C6 glioma cells in culture, but reduction of CaM expression was found to inhibit their growth. The antiproliferative effects exerted by CaM inhibitors have also provided a substantial body of evidence that suggests an association of CaM with growth responses. Several CaM inhibitors have been tested to date. Schuller et al. (1991) found that B859-35, which is a dihydropyridine derivative, markedly inhibited proliferation of three human lung cancer cell lines. Hait et al. (1994) reported that several phenothiazine antipsychotic drugs inhibit CaM and also the proliferation of C6 glioma cells. They also found that the antiproliferative effects...

Calmodulin in Neoplasia

An enhancement of CaM has been recognised as a feature of cell transformation and of malignant cells. CaM levels of human lung cancer cells are higher than that of benign tumours of the lung or normal lung tissue (Liu G.X. et al. 1996). These authors also describe a correlation between tumour grade and TNM stage and levels of CaM. However, Edelman et al. (1994) have described a CaM-like protein that is apparently restricted to epithelial cells. This CaM-like protein was identical in size and largely homologous to CaM, but, unlike CaM, its expression seems to be significantly lower in malignant cells.

CHD Is an Inflammatory Disease

Most investigators agree that atherosclerosis is a chronic low-grade inflammatory disease.26 Proinflammatory factors (free radicals produced by cigarette smoking, hyperhomocysteinemia, diabetes, peroxidized lipids, hypertension, elevated and modified blood lipids) contribute to the injury to the vascular endothelium, which results in alterations of its antiatherosclerotic and anti-thrombotic properties. This is thought to be a major step in the initiation and formation of arterial fibrostenotic lesions. From a clinical point of view, however, an essential distinction should be made between unstable, lipid-rich and leukocyte-rich lesions and stable, acellular fibrotic lesions poor in lipids, as the propensity of these two types of lesion to rupture into the lumen of the artery, whatever the degree of stenosis and lumen obstruction, is totally different.

Thoracic Aortic Aneurysms

Thoracic aneurysms are most commonly located in the ascending and descending thoracic regions (Fig. 7.10). The more difficult transverse arch and thoracoabdominal locations are also less common. Several etiologies exist for chronic aortic aneurysms. The most common cause is atherosclerotic degeneration of the aorta (Fig. 7.11a-d), usually occurring in elderly smokers. Chronic aortic dissection (Fig. 7.12a-c), Marfan's syndrome (Fig. 7.13a-c), cystic medial necrosis or aortitis secondary to syphilis or granuloma are other etiologies.

Cancer Is a Global Problem

Ences among developing and developed countries in the incidence rates of certain cancers, lung cancer is the most common cancer among men in both regions of the world and breast cancer is the most common cancer in women (Fig. 3-4).5 There are, however, regional differences in the distribution of various cancers in different regions of the world that reflect differing etiologic factors. For example, infectious etiology plays a greater role in certain parts of the world, e.g., the role of schistosomiasis infections in causing bladder cancer in parts of Africa and that of hepatitis B infections in liver cancer in China

Paraneoplastic Syndromes Of The Nervous System

The presence of these antibodies has been associated with small cell lung cancer (SCLC) in about 90 of patients with this type of neoplasm. Nevertheless, 1520 of patients harbor these antibodies without having paraneoplastic syndromes. The onconeural antigen termed Hu antigen refers to a family of predominantly nuclear proteins expressed in all neurons of the central and peripheral nervous system. The Hu antigen corresponds to a set of proteins with a molecular weight of 35-40 kD expressed both in neurons and SCLC cells 26 , The Hu proteins constitute a family of RNA-binding proteins (HuD, HuC, Hel-Nl. and Hel-N2) characterized by an RNA recognition motif of about 80 amino acids. All Hu proteins are thought to have a role in the development and maintenance of the nervous system because of their restricted expression in neurons and their homology to the drasophila protein elav 27 , The anti-Hu antibodies have shown specific binding capacity to neurons in both the central and peripheral...

Leptin and Cancer Anorexia Cachexia

The persistence of anorexia and the onset of cachexia in cancer patients, therefore, implies a failure of this adaptive feeding response 86 . Leptin, a member of the gp 130 family of cytokines, induces a strong T helper-1 lymphocyte response and is regarded as a proin-flammatory inducer 87 . Several data suggested a role of leptin in inflammatory diseases. Proinflammatory cytokines up-regulate leptin expression in white adipose tissue and increase plasma leptin levels in hamsters and mice 88 . However, in many common diseases associated with cachexia, such as chronic obstructive pulmonary disease and chronic inflammatory bowel disease, there is an inflammatory status caused by high proinflammatory cytokine levels, whereby leptin concentrations are decreased related to body fat mass. In patients with advanced non-small-cell lung cancer, serum leptin levels were lower than in controls and lower still in those who were cachectic who also showed an increase of...

Epidemiologic Risk Factors

In addition to age over 50 and Caucasian race, an increased number of ovulatory cycles appears to increase risk for ovarian cancer, reflected in an association with early menarche, late menopause, and nulliparity (Berek and Bast 2006). Conversely, factors that decrease the number of ovulatory cycles, including repeated pregnancies, prolonged breast feeding and use of oral contraceptives, decrease the risk of ovarian cancer. A protective effect from tubal ligation suggests that exogenous carcinogens might gain access to the ovary from the uterus through the fallopian tube. However, evidence for viral or strong chemical carcinogens has not been obtained, with the possible exceptions of the use of talc products in all histotypes and of cigarette smoking in mucinous cancers, but not in the more common serous histotype (Berek and Bast 2006). Approximately 10 of ovarian cancers are familial and are associated with mutations in BRCA1, BRCA2 or, less frequently, with the mismatch repair...

Aging and the Incidence of Cancer

Ever, many exceptions to the age-cancer relationship. Lung cancer brought on by cigarette smoke and childhood leukemias are the most notable examples. The chemicals in cigarette smoke are known to accelerate tumor formation, but the factors responsible for cancer acceleration in children are still unclear.

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

Other Tissue Autoantibodies

Tion between neoplasia and autoimmunity results from increased incidence of both conditions in senescence. In our preliminary investigation 61 we studies 139 patients (55 of whom were aged 60 years and younger, and 84 were older than 60 years) suffering from a variety of malignant tumors for ANA, RF and antiery-throcyte antibodies (Coomb's test). There was no significant difference between the incidences of ANA and RF in the young patients and in the young controls and similarly, there was no significant difference between the incidences of ANA and RF in the elderly cancer patients and in the elderly controls. Our results suggest that the reported high incidence of ANA and RF in malignancies is a result of the old age of these patients rather than the tumor itself. However, the incidence of antierythrocyte antibodies was significantly higher in the patients than in the controls. This study was later extended to test a large battery of autoantibodies and the malignancies were grouped...

Cell Surface Adhesion Molecules

From the evidence discussed so far, it would be natural to assume that well differentiated, non-invasive and non-metastatic carcinomas will express normal or relatively high levels of cadherins, whereas tumours that are poorly differentiated and possess a high metastatic potential will not. This correlation has been shown to hold true for several tumour types including squamous cell carcinomas of the head and neck (49), lung cancer (50), prostate and bladder carcinomas (51, 52), pancreatic cancer (53) and lobular breast cancer (29).

Dietary Nutritional Factors

Vitamin E (alpha-tocopherol) is a fat-soluble potent intracellular antioxidant occurring in lettuce, watercress, and cotton- and hemp-seed oil. In the Finnish alpha-tocopherol beta-carotene (ATBC) trial, 29,133 male smokers aged 5069 years were randomly assigned to receive al-pha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (Heinonen et al. 1998). However, in this study prostate cancer was only looked at as a secondary end point. A 32 decrease in the incidence and a 41 decrease in mortality from prostate cancer was observed among the subjects receiving al-pha-tocopherol compared with those not receiving it. Notably, among men receiving beta-carotene, prostate cancer incidence was 23 higher and mortality was 15 higher compared with those not receiving it. Despite these data, results from other epidemiologic studies do not support a general protective effect of vitamin E. been confirmed by higher serum levels or urinary concentrations of...

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.

Hyaluronan in Emphysema

Evidence relating HA to emphysema is accumulating. Konno et al. (114) found HA to be decreased in emphysematous lungs. Data from animal models show that HA is involved in cigarette smoke-induced emphysema and in elastase-induced emphysema. Guinea pigs exposed to tobacco smoke have reduced levels of lung HA (115). Cantor et al. (116) showed that instillment of hyaluronidase and the addition of 60 oxygen, which is a non-toxic concentration of oxygen, produced air-space enlargement. They also showed that prior hyaluronidase treatment increased the effect of elastase instillment (117), an observation that was confirmed by Murakami et al. (118). Further, HA protected elastin fibers in vitro and lead to a decrease in air-space enlargement caused by elastase instillment in vivo (119).

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

Smoking and Cardiovascular Diseases

In the first half of the last century German clinicians were among the first who contributed to our knowledge on the relationship between smoking and lung cancer.6 The classical epidemiological studies on this relationship were started at the end of the 1940s and the beginning of the 1950s in England and in the US. A cohort study of 34,000 British male physicians was started by Doll et al. in 1951 with follow-up periods of 20, 40, and 50 years.7-9 For the 20-year follow-up, the relative risk for smokers compared to non-smokers of developing lung cancer was 14. On the other hand, the relative risk for the relationship between smoking and coronary heart disease (CHD) mortality turned out to be only 1.6. Because of the greater number of deaths from CHD compared to those from lung cancer the attributable risk for smoking and CHD was nearly twice as big as the respective figure for smoking and lung cancer (Table 27-2). With these data, Doll and Peto could show that a reduction in smoking...

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

Smoking and Acute Myocardial Infarction Mechanisms

Tobacco smoke is a complex mixture of aerosols and particulate matter containing about 4000 different chemical compounds of which many are highly toxic and more than 40 are carcinogenic. Tobacco smoke interferes with the cardiovascular system in the following ways Smoking increases the risk of thrombosis by increasing platelet aggregation, blood viscosity, and fibrinogen levels. C-reactive protein, a marker of inflammation, is also increased by cigarette smoking. The inhaled carbon monoxide produces carboxyhemoglobin, which leads to an imbalance between oxygen demand of and supply to the myocardium. Polycyclic aromatic hydrocarbons (PAH) and other toxic compounds damage the endothelium. LDL cholesterol is oxidized by cigarette smoke and it is the oxidized LDL cholesterol which exerts its atherogenic effect. VLDL cholesterol and triglycerides are also increased by inhaled cigarette smoke. In addition, cigarette smoke decreases the protective HDL cholesterol.

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

Nonspecific Tumor Markers

CYFRA 21-1 appears to be a useful marker for non-small cell lung cancer (NSCLC), especially the squamous type with a sensitivity of 55 . Increased levels correlate with the severity of the disease (41). In a group of squamous-cell lung cancer patients at different stages of disease, measurement of CYFRA 21-1 and SCC have showed significant prognostic value for clinical stages. A significant relationship between marker level and survival was observed for CYFRA 21-1 as well as SCC levels. In a multivariate analysis, CYFRA 21-1 and or TPS remained significant predictors of survival (42). The Combination of proliferation markers with other tumor markers appears most effective. Combination of CYFRA 21-1 and NMP22 help determine the need for cystoscopy in patients with bladder cancer (43).

Effects of Type of Intervention

Advice given by physicians is effective for smoking cessation.2 Interventions involving professionals from different disciplines have more effect than interventions carried out by professionals from a single discipline.2 In their Cochrane review of interventions by nurses in the area of smoking cessation, Rice and Stead indicate that intensive telephone support after discharge from hospital is an essential component of an effective intervention for heart patients.3 Brief advice given by nurses to patients with a coronary bypass is also effective. Patients with a myocardial infarct are twice as likely to be successful in stopping than are patients after a bypass operation.4 Table 29-1. Nicotine withdrawal symptoms according to the criteria of DSM-IV

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...

Antidepressants and Other Pharmacotherapy

The withdrawal symptoms of smoking cessation can be stress, depression, anxiety, anger, insomnia, and weight gain. For that reason antidepressants can be helpful.10 old for seizures it is contraindicated in patients who are at risk for seizures. The daily dose is 150mg day for 6 days, then 150mg twice a day. In those predisposed to seizures, in elderly people, or those with decreased kidney or liver function, the maintenance dose should be taken once a day only. Smoking cessation starts about 10 days after the start of medication.9 An overview of drugs used for smoking cessation, contraindications and side-effects is given in Table 29-4. Nortriptyline is an antidepressant with serotonergic and norepinephrenic activity. This antidepressant is not approved as a smoking cessation aid but is recommended in many public health services guidelines for smoking cessation. The daily dose is 25 mg day for 3 days, then 50 mg day 4 days, then 75-100 mg day. Smoking cessation starts from the tenth...

Test JoeReference Ranges

Since the troponin I and CK-MB levels are below the medical decision limits, the ED physician reassures Mrs. Smoker that Joe is not having a heart attack. However, the elevated BNP indicates Joe has CHF. The physician counsels Joe to stop smoking, increase his exercise level, eat a diet low in fat, and take his medications. He provides information on a smoking cessation program and refers Joe back to his cardiologist for continued therapy.

Comprehensive Database Searching

Checking public patented proteins at 88,019 sequences gave no hits. However the patent nucleotide division, gbPAT, at 581,001 sequences, gives three solid hits, AX321627, AX192589 and AX072029. The first of these is a 2114-bp DNA from patent WO0172295. The document indicates this protein was isolated from a lung cancer sample (http ep. ). These hits constitute a partial mRNA level of confirmation for the novel protein but a reciprocal check (i.e. a BLASTN of AX321627 against the nr nucleotide database) indicates this clone may be a chimera from two separate gene products. A search against a commercial patent database, containing 673,453 protein sequences, reveals identity matches for the N-terminal section from patent WO200060077 and a C-terminal identity match from WO200055350, both of which are reported as cancer-associated transcripts Checking the GSS division by TBLASTN gives four genomic hits AZ847251 from mouse, AG114530 from chimpanzee, BH306228 from rat and...

Monitoring Of Cancer Patients

Persisting antibodies were diagnosed with prognosti-cally poor tumor stage III IV - 30 of the patients from the respective seronegative group, however, survived. For lung cancer patients, it was shown that p53AAb present at the time of carcinoma diagnosis may persist during disease progression 90 . p53AAb levels in one patient with tracheal chondromata increased over a period of 2 years concomitantly with tumor development until clinical lung cancer diagnosis therapeutical intervention by chemotherapy was paralleled by a sharp decrease in p53AAb 51 . The usefulness of p53AAb in trailing therapy was investigated by a study on 16 seropositive patients with inoperable lung cancer 88 . A substantial decrease in p53AAb during therapy was noted for 12 patients - four had unchanged p53AAb levels or a decrease of less than 50 . Since chemotherapy can eventually lead to (partial) immunosuppression, the authors addressed the questionable specificity of the observed p53AAb drop by simultaneous...

Industrial Chemicals and Occupational Cancers

The chemicals and industrial processes that have a known or suspected etiologic role in the development of cancer are listed in Table 3-6. As noted above, about 2 -5 of all cancer deaths are attributed to occupational hazards. Of those agents listed as carcinogenic for humans, a number were identified because of their close association between an abnormal clustering of certain cancers and exposure to an industrial chemical or process. For example, epidemiologic studies of workers occupationally exposed to industrial levels of 4-aminobiphenyl have a higher incidence of bladder cancer.80 Occupational exposure to asbestos fibers results in a higher incidence of lung cancer, mesotheliomas, gastrointestinal tract cancers, and laryngeal cancers.81 As mentioned earlier, cigarette smoking and occupational exposure to asbestos act synergistically to increase the incidence of lung cancer. Several epidemiologic studies have shown increased frequency of leukemia in workers exposed to...

Calbindin Expression And The Metastatic Phenotype

The ability of steroids to influence the expression of calbindins has led to investigations aimed at examining their potential involvement in the development and growth of tumours, their progression, and prognosis. Watanabe et al. (1994) investigated CBD levels of lung cancers. The levels of CBD were low in normal lung tissue, but its expression was higher in lung cancers, with SCLC tissue expressing greater amounts than non-SCLC (NSCLC). Furthermore, CBD levels correlated with progression of NSCLC to advanced stages of the disease involving metastatic involvement of the lymph nodes. Upon investigating cell lines derived from these tumours, Watanabe et al. (1994) noticed that CBD expression might also relate to the expression of neuroendocrine-related paraneoplastic properties of these tumours. They found that the CBD could be used to differentiate classical SCLC from variant Significant differences also have been noted in the expression of CBD in human colonic cell lines derived from...

Detection Of A Malignant Disease

From all the reports on p53 autoantibodies it seems to come up that p53 autoantibodies are in general associated with a malignant disease, whereas, healthy blood donors are rarely positive for p53 autoantibodies. Two individuals were found to express p53 autoantibodies although no tumor was detected. Both individuals were heavy smokers and diagnosed for chronic cough or a benign obstructive tracheal tumor. Both developed lung cancer within 5 or 15 months, respectively 27 . In a study of patients with prostate carcinoma, a healthy control patient was also positive for p53 autoantibodies 28 , Later, it turned out that this patient died from an undetected lung cancer. Thus, these studies might indicate that p53 autoantibodies may be early markers for malignancy and that this type of analysis allows for the detection of an unknown cancerous malignancies. However, there are also reports that p53 autoantibodies were found in patients with nontumorous diseases such as autoimmune diseases....

Air and Water Pollutants

Air, water, and soil pollution is estimated to account for only 1 -4 of all cancers. A small percentage of lung cancer (less than 5 ) may be due to chronic inhalation of outdoor air pollutants such as industrial or engine exhaust chemicals. Indoor air pollutants such as secondhand smoke and radon are thought to be contributors, but this risk is most likely exaggerated (see below). In China and some other Asian countries, chronic inhalation of cooking oil smoke may be a causative agent of lung cancer.90 The contamination of the atmosphere by chlorofluorocar-bons (whose production is now banned in developed countries) in refrigerant and propellants has been implicated in destruction of the ozone layer and a resultant increase in skin cancer due to a lower filtering of UV irradiation from the sun. Occupational exposure to inhaled asbestos, such as occurred in Liberty Ship building in World War II, has been clearly linked to me-sothelioma. cancers) for any given level of low-dose...

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.

Carbon Monoxide Poisoning

Carbon monoxide (CO) is the most commonly encountered toxic gas. It is an odorless gas that is a by-product of incomplete combustion of carbon, such as from burning of natural gas, gasoline, or other petroleum products. It is present in exhaust from automobile engines or natural gas furnaces or water heaters. It also is a product of structure fires, and so a commonly encountered toxin in firefighters. It is a by-product of cigarette smoking both for the smoking individual and for those inhaling secondhand smoke. People become exposed through these routes, especially from auto exhaust, gas leaks, or secondhand smoke.

Clinical Presentation

Dyspnea 011 exertion is the most sensitive symptom for the diagnosis of CHF, but its specificity is much lower. Other symptoms, which are common but less sensitive for the diagnosis, include dyspnea at rest, anxiety, orthopnea, paroxysmal nocturnal dyspnea, and cough productive of pink, frothy sputum. Nonspecific symptoms sometimes reported are weakness, lightheadedness, abdominal pain, malaise, wheezing, and nausea. Patients may have a medical history of hypertension, coronary artery disease, or other heart diseases (cardiomyopathy, valvular disease). Histories of cigarette smoking and alcohol abuse may also be found.

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...

Bisphosphoglycerate compound also called glycerate23bisphosphate has two important

As Figure 7. shows, 2,3-BPG binds in the cavity between the fi chains of lemoglobin, making electrostatic interactions with positively charged groups surrounding this opening. Comparison of the two hemoglobin conformations shown in Figure 7.12b shows that this opening is much narrower in oxyhemoglobin than in deoxyhemoglobin. In fact, 2,3-BPG cannot be accommodated in the oxy form. The higher the 2,3-BPG content in red blood cells, the more stable the deoxy structure will be. The decrease in O2 affinity by hemoglobin is explained by stabilization of the deoxy structure. Increased 2,3-BPG levels are also found in the blood of smokers, who because of the carbon monoxide in smoke also suffer from limitation in oxygen supply.

The Approach To The Patient With A Lung Mass

A general laboratory work-up of the patient with a lung mass includes CBC and electrolytes. The fundamental work-up of lung mass then includes sputum cytology, CT scan of the chest and flexible fiberoptic bronchoscopy. These three tests should be included in the preoperative evaluation of all lung masses. CT scan is useful for a number of reasons, not only to further define the location and extent of the lung lesion, but also to identify any synchronous lesions that may have been missed on the chest x-ray. Most importantly the CT evaluates for mediastinal adenopathy, the presence of which may require investigation. The use of CT scanning as a modality for staging of lung carcinoma is controversial. In general, in the United States the standard of care for staging of lung carcinoma is by CT scan. Mediastinal nodes greater than 1.0 cm require further evaluation. Node enlargement may represent either reactive inflammation or may represent involvement with carcinoma. Further assessment of...

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,...

Comorbidity and Special Issues That Influence Interpretation of BNP

The presence of concomitant pulmonary disease does not diminish the utility of the BNP test in distinguishing patients with heart failure from those without heart failure. Morrison et al. (24) showed that rapid testing of BNP could differentiate pulmonary from cardiac etiologies of dyspnea. Some types of pulmonary disease that provoke significant increases in wall stress in the right heart, such as cor pulmonale, lung cancer, and pulmonary embolism (PE), are associated with elevated levels of BNP. However, the magnitude

Segmentectomy Versus Lobectomy

The standard lung cancer operation for a tumor confined to a lobe of the lung is a lobectomy rather than a segmental resection. However, there is evidence that in some situations a segmentectomy may result in similar long-term survival as a lobectomy. This is important in a patient with limited pulmonary function in whom a lobectomy will result in a poor predicted postoperative FEV-1. In these segments a segmentectomy may permit resection of the lesion in an anatomical

The Great Cancer Myths

These authors have developed charts for men and women that show the chance of dying from various causes based on age and smoking history (Figs. 3-11 and 3-12). Instead of giving risks in terms of population percentages, these data show risk in terms of individual risks. For example, their data indicate that a 60-year-old woman, even one who smokes, has a 4.5 chance of dying of a heart attack in the next decade, a 6.5 chance of dying of lung cancer, and a 0.7 chance of dying of breast cancer. Or to look at it another way, for every 1000 60-year-old women who are smokers, 45 will die of heart attacks, 65 of lung cancer, and 7 of breast cancer in the next 10 years. For 60-year-old women who have never smoked, 14 of 1000 will die of heart disease, 5 of lung cancer, and 7 of breast cancer by the time they reach 70 years of age. For 60-year-old men who are smokers, 84 of 1000 will die of heart disease and 98 of lung cancer, but only 4 of 1000 will die of prostate cancer. cigarette smoking,...

Clinical Approach

The most common etiology for COPD is inhalation injury, specifically cigarette smoking. Another important cause is a,-antitrypsin deficiency, which is hereditary. The disease may become evident by age 40 years and often occurs without cough or smoking history. Therapy by replacement of a,-antitrypsin enzyme is available. Characteristically, patients with COPD present with progressively worsening dyspnea (first on exertion, then with activity, then at rest). Patient may vary in appearance from a blue bloater (chronic bronchitis, overweight, edematous, cyanotic) to a pink puffer (emphysema, thin, ruddy cheeks).

T3 Chest Wall Involvement

Chest wall invasion by lung carcinoma occurs in approximately 5 with a 5 year post-resection survival rate of approximately 1 in 3 when regional lymph nodes are negative. There is general agreement that full thickness chest wall resection is indicated in patients with nonsmall cell lung cancer invading the chest wall. There is some disagreement if the tumor extension appears to involve only the parietal pleura. Some feel that an extrapleural dissection should be attempted and if a plane is readily achieved, then only an extrapleural resection should be performed without chest wall resection. However most feel that if the parietal pleura is involved then formal chest wall resection is indicated. The role of adjuvant radiation therapy has not yet been defined.

Superior Sulcus Tumors

Superior sulcus tumors by definition are T3 disease (at least), and are Stage Illb if there is no nodal disease (N0), or Stage Ilia if there is intrapulmonary node involvement (N1). The management of superior sulcus tumors is important since this is perhaps one of the few stage III types of lung cancer that may actually be cured by surgery.

The Team Approach

The next time that the student was in the laboratory, he searched for additional information about Mr. Layne. Mr. Layne was referred to a registered dietitian for nutritional therapy and received instructions for an exercise program. The primary objective or goal for the clinical treatment of an individual with metabolic syndrome is first, to reduce the risk of clinical atherosclerotic disease, and second, to decrease the risk of developing type 2 diabetes mellitus. Generally, reducing the risk for the former involves reducing the major risk factors cigarette smoking and low-density lipoprotein (LDL) cholesterol, blood pressure, and or plasma glucose levels.26 Due to the likely presence of abdominal obesity, weight loss is a necessary first step.

Applications In Environmental Analysis

An integral part of environmental analysis in air is the examination of the presence of amines (mainly heterocyclic) in an atmosphere polluted with cigarette smoke. Epidemiological studies have shown that cigarette smoking is associated with the development of human cancers, and cigarette smoke condensate has been known to be mutagenic in bacteria and carcinogenic to experimental animals. Cigarette smoke contains various pyrolysis products. Among them are known patent mutagens and carcinogens such as volatile N-nitrosamines, tobacco-specific nitrosamines, polycyclic aza-arenes, and mutagenic and carcinogenic heterocyclic amines.7 Figure 11.17 shows an example of a chromatogram of AAs in Kentucky cigarettes, while Table 11.16 compares the results of a determination of AA amounts in ng cigarette using the new SPE method, ISO method, and some other references.

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...

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