The Painless Stop Smoking Cure

Quit Smoking Magic

Mike Avery is the author of the quit smoking magic program. He is an ex-smoker (20 year habit) and a researcher who has carried out lots of tests on this topic for many years. He used himself as a test subject, after trying everything you can think of to stop smoking. He then tested his quit smoking magic theory on himself and got the results needed. Mike Avery's program of quit smoking magic has successfully helped hundreds of people all over the world quit smoking, including his family members and co- workers. He should be trusted because he has been in the shoes of being a smoker and has cured himself from smoking addiction. So if you are planning on doing the same, you should go to the one person who understands what you are going through. This program will provide you with information about smoking in general and ways on how to stop the smoking addiction from eating you up. Its contents are based on real-life experiences rather than theories that were imagined by someone. It is an e-book program on the subject of quitting smoking and comes with three different bonus e-books on the following topics; how to whiten your teeth, end bad breath and how to clean your lungs. Purchasing this program does not require you to have any technical skill to be able to use it, it only requires you to read and understand. More here...

Quit Smoking Magic Summary


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All of the information that the author discovered has been compiled into a downloadable pdf so that purchasers of Quit Smoking Magic can begin putting the methods it teaches to use as soon as possible.

I give this ebook my highest rating, 10/10 and personally recommend it.

Treatment of Lung Cancer Associated Anemia 161 Transfusions

Historically, treatment options for patients with lung cancer who develop severe or symptomatic anemia were primarily limited to RBC transfusions. In fact, most physicians still do not treat, unless with RBC transfusion, in case of severe anemia (5). Although RBC transfusion is the most rapid correction, especially useful in patients with severe or life-threatening anemia, several risks are associated with it, including acute transfusion reactions and transmission of infectious agents (71,72). Furthermore, the limited availability and the cost of transfusion products limit their use. Finally, there is the concern of decreased immunosurveillance of tumors by the recipient of allogeneic transfusion. A negative impact on outcome has been described in some but not all surgical series examining this issue in lung cancer (73) and other cancer types (74,75). Another treatment option for the management of anemia is the administration of rHuEPO. The Food and Drug Administration (FDA) approved...

Nonsmall Cell Lung Cancer

Randomized Studies on the Primary Use of White Blood Cell Colony-Stimulating Factors in Chemotherapy for Advanced Nonsmall-Cell Lung Cancer Randomized Studies on the Primary Use of White Blood Cell Colony-Stimulating Factors in Chemotherapy for Advanced Nonsmall-Cell Lung Cancer

Other environmental risk factors that may predispose smokers to COPD

In addition to cigarette smoking a number of environmental factors have been identified which impact on lung function (FEV1) and may therefore predispose to the development of COPD. These are summarized in Table 26.4. The identification of low birth weight (Barker et al., 1991), childhood respiratory tract infections (Burrows et al., 1977b Colley et al., 1973 Kiernan et al., 1976) and childhood passive smoke exposure (Lebowitz et al., 1987 Wang et al., 1994) as factors that may contribute to the pathogenesis of COPD suggests that the disease may begin in childhood. However, these observations are often derived from retrospective studies and the results need to be interpreted with caution (Phelan, 1984). In adults, increased expression of adenovirus protein in smokers with emphysema has provided evidence that latent viral infection may amplify the inflammatory response to cigarette smoke and contribute to the development of emphysema (Retamales etal., 2001). Occupational exposure to...

Tumor antigens expressed by lung cancer

Numerous tumor antigens have been described for lung cancers. Among the most frequently expressed are the MAGE antigens with MAGE-1 reported in 11-36 , MAGE-2 in 30 , MAGE-3 in 38 -60 , and MAGE-4 in 13 of NSCLC (28-31). Using tissue microarray technology, expression of tumor-associated antigens (TAAs) of the MAGE family have been reported in 50 of squamous cell carcinomas of the lung and in 38 of large-cell carcinomas of the lung (32). In another study, MAGE-A10 was expressed only by SCLC, and MAGE-A1, 3, 6, 12, and 4b were expressed by both SCLC and NSCLC (33). CTLs derived from regional lymph nodes of lung cancer patients can recognize MAGE peptide epitopes (34). Other described antigens include NY-ESO-1 (35,36), Wilms' tumor-1 (WT1) (37,38), translation initiation factor eIF-4G (in squamous cell carcinomas) (39), carcinoembryonic antigen (CEA) (38), and Mac-2 binding protein (40). Overexpression of HER2 neu is controversial. Although reported in 4-60 of NSCLC (primarily...

Lung Cancer Treatment

EGF receptor regulates the growth of many types of cells. EGF receptor overexpression is common in lung cancer. The EGF receptor can be blocked by an Ab such as the human-chimeric MAb cetuximab that binds to its extracellular domain or by small molecules such as gefitinib, a reversible inhibitor of EGF receptor tyrosine kinase (94,99). In two large phase 2 trials of patients previously treated with chemotherapy for nonsmall-cell lung cancer (NSCLC), response rates of up to 19 were reported for gefitinib (100,101).

Small Cell Lung Cancer

Randomized Studies Focusing on the Primary Administration of White Blood Cell Colony-Stimulating Factors in Small-Cell Lung Cancer Randomized Studies Focusing on the Primary Administration of White Blood Cell Colony-Stimulating Factors in Small-Cell Lung Cancer Randomized Studies on the Primary Use ofWhite Blood Cell Colony-Stimulating Factors in Standard-Dose Chemotherapy for Small-Cell Lung Cancer Randomized Studies on the Primary Use ofWhite Blood Cell Colony-Stimulating Factors in Standard-Dose Chemotherapy for Small-Cell Lung Cancer Randomized Studies on the Primary Use ofWhite Blood Cell Colony-Stimulating Factors to Increase Dose Intensity of Chemotherapy for Small-Cell Lung Cancer

Summary and challenges to vaccines for lung cancer

Lung cancers, like other malignancies, can escape immune recognition by downregulation of HLA class I molecules. Administration of IFN-gamma has been shown to upregulate HLA class I on NSCLC and thus may be a useful adjunct (37). Fas-ligand (Fas-L), frequently detected in lung carcinoma cell lines and resected tumors, can cause apoptosis of T cells. In fact, lung carcinoma cells were capable of killing the Fas-sensitive human T-cell line Jurkat in coculture experiments (65). Inhibiting Fas-L expression by tumors might therefore be a useful adjunct to immunotherapies. The tumor antigen RCAS1, positive in 47 of NSCLC specimens (and up to 80 of adenocarcinomas), induces apoptosis in immune cells bearing the RCAS1 receptor (66). Interference with its activity might improve the activity of lung cancer immunotherapy. Lung cancers may negatively regulate DC differentiation and this observation supports the use of ex vivo-generated DCs in vaccine strategies (67). Lung cancer cell lines...

Presence of Antitumor Immunity in Lung Cancer Patients

Despite immune defects, antitumor immune responses can be detected in some lung cancer patients. For example, more than half of SCLC and NSCLC patients have been described to have circulating antibodies reactive with autologous tumor proteins (9). Presence of these antibodies predicts better response to therapy and survival in some studies (9-11), whereas others, such as those specific for p53, are associated with a survival effect in some but not other studies (12-20). Detecting in vivo antigen-specific T-cell responses in lung cancer patients has been more challenging. Lymphocytes from regional lymph nodes draining lung cancers proliferate in response to autologous tumor to a greater extent than do peripheral blood lymphocytes (8,21), suggesting enrichment for tumor-specific effectors in regional lymph nodes. Tumor-infiltrating lymphocytes from lung cancers have been discovered to have a restricted T-cell receptor V-beta usage (22), a marker for the oligoclonality expected with an...

Lung cancer

Apart from non-melanoma skin cancer, lung cancer is the most common cancer in Australia both in terms of incidence and death, accounting for at least 20 of cancer deaths. 1 In the United States it accounts for 35 of cancer deaths in men and 21 of deaths in women. Only 10-25 are asymptomatic at the time of diagnosis but lung cancer can cause an extraordinary variety of clinical symptoms and signs with a reputation for several paraneoplastic syndromes. The paraneoplastic syndromes include hypercalcaemia, Cushing's syndrome, carcinoid syndrome, dermatomyositis, visual loss progressing to blindness from retinal degeneration, cerebellar degeneration and encephalitis.

The Scope Of Biosurveillance

We also decided against disease surveillance and public health surveillance because these terms, to an epidemiologist, connote surveillance for noninfectious disease, child mortality, injury, cigarette smoking, and dental diseases such as enamel fluorosis (CDC, 2005). To keep what was already a very large topic manageable, we decided against discussing surveillance for these conditions. The principles and techniques that we discuss, nevertheless, apply to surveillance for any disease or condition.

Abnormal Involuntary Movement Scale

Tardive dyskinesia is a syndrome characterized by abnormal involuntary movements of the patient's face, mouth, trunk, or limbs, which affects 20 -30 of patients who have been treated for months or years with neuroleptic medications. Patients who are older, are heavy smokers, or have diabetes mellitus are at higher risk of developing TD. The movements of the patient's limbs and trunk are sometimes called choreathetoid, which means a dance-like movement that repeats itself and has no rhythm. The AIMS test is used not only to detect tardive dyskinesia but also to follow the severity of a patient's TD over time. It is a valuable tool for clinicians who are monitoring the effects of long-term treatment with neuroleptic medications and also for researchers studying the effects of these drugs. The AIMS test is given every three to six months to monitor the patient for the development of TD. For most patients, TD develops three months after the initiation of neuroleptic therapy in elderly...

Anticarcinogenic Activity

A review of carotenoid research by the International Agency for Research on Cancer suggests there is sufficient evidence that beta-carotene has cancer-preventive activity in experimental animals, based on models of skin carcinogenesis in mice and buccal pouch carcinogenesis in hamsters (Vainio & Rautalahti 1998), despite a review suggesting that beta-carotene does not protect against lung cancer in animals (De Luca & Ross 1996). None of these mechanisms has been conclusively found to contribute to preventing cancer in vivo and there is ongoing debate as to the role of beta-carotene in cancer prevention (Cooper et al 1999, Patrick 2000). This debate has been further fuelled by the findings of two large intervention studies, the Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study (the 'Finnish study' Heinonen et al 1994) and the Carotene and Retinol Efficacy Trial (CARET Omenn et al 1996a), which found a significantly increased risk of lung cancer in high-risk...

Cardiovascular Disease

Epidemiological studies support the idea that a diet rich in high carotenoid containing foods is associated with a reduced risk of heart disease (Kritchevsky 1999). A review of observational and intervention studies on beta-carotene and the risk of coronary heart disease found that seven cohort studies (Gaziano et al 1995b, Gey et al 1993, Knekt etal 1994, Manson etal 1991, Morris et al 1994, Rimm et al 1993, Street et al 1994) reported relative risks between 0.27 and 0.78 for high serum beta-carotene levels or high dietary intake and that this was supported by case-control studies (Bobak et al 1998, Bolton-Smith et al 1992, Kardinaal et al 1993, Torun et al 1994, Tavani et al 1997) that reported odds ratios between 0.37 and 0.71, with a possible stronger protection for current smokers (Tavani & La Vecchia 1999). These results contrast with those of four more recent cohort studies (Knekt et al 1994, Kushi et al 1996, Pandey et al 1995, Todd et al 1995) and five large RCTs (Buring...

Tailoring Treatment Programs

''Tailoring'' refers to deliberate attempts to account for important individual or subgroup variables when developing program messages or intervention strategies (91). The concept of tailoring has particular relevance to theories that incorporate contextual factors as primary intervention variables as opposed to those that tend to subordinate the importance of contextual issues in favor of greater emphasis on self-control. As reviewed by Rakowski (91), the concept of tailoring has evolved to a high level of specificity with respect to how tailoring can be approached and why it might work where other approaches have failed (91). Many of the relevant variables are culturally determined, although this is implicit rather than directly argued. According to Rakowski, key principles are the need for prior knowledge of the constellation of variables that predict individual variation in a given behavior, and the context specificity of these variables to the interaction of behavior, population,...

Effects On Microcirculation And Nitric Oxide

A double blind, dose-finding study found that flavanol-rich cocoa increased circulating NO species in the plasma of male smokers, with maximal effects seen with ingestion of 176-185 mg flavanols (Heiss et al 2005). Another double-blind trial found that ingestion of a high-flavanol cocoa drink, but not a low-flavanol one, enhanced NO bioactivity and increased plasma concentrations of nitroso compounds 2007 Elsevier Australia

The Nature Of The Concern

This brings us to issue of the legitimacy of discriminatory practices. At the heart of this are the broadly complementary notions of merit and desert. Both of these fail to make sense without some account of responsibility and choice. Where an individual makes particular lifestyle choices, smoking tobacco for example, which have a negative influence on their health they share some responsibility for those outcomes. The extent of this responsibility is the subject of a great deal of debate, nonetheless, I think it is clear that the smoker is in some sense complicit. Equally, though it may prove practically difficult, it makes sense to ask the smoker to desist, and perhaps even make the performance of particular medical procedures contingent upon just such an attempt. Similarly, were an insurance company offering health cover to charge higher premiums of smokers, there would not be an in principle objection. Smoking is something the individual has control over, and consequently can take...

Glycocholate Breath Test

Breath test is a simple, inexpensive, and noninvasive technique to diagnose SBBO. The lactulose breath test is performed after 12 hours fasting previous to the test. Hydrogen breath samples are taken at baseline, and subsequently every 10-30 minutes after the test meal that contains 10-12 g of lactulose. The hydrogen breath samples are analyzed gas chromatographically (81). Baseline samples average 7.1 +5 parts per million (ppm) of H2 and 0-7 ppm for CH4 (82). Values of the baseline sample over 20 ppm H2 are suspect for bacterial overgrowth. Values between 10 and 20 suggest incomplete fasting before the test or ingestion of slowly digested foods the day before the test, the colon being the source of the elevated levels (82). Slowly digested foods like beans, bread, pasta, and fiber must not be consumed the night before the test because these foods produce prolonged hydrogen excretion (82). The patient is not allowed to eat during the complete test. Antibiotics and laxatives must be...

Cholinergic Mechanisms

Application of nicotine to intrathoracic autonomic neurons can alter their activity (68) and induce concomitant changes in regional cardiac function, whether the neurons are located in extracardiac or intrinsic cardiac ganglia (68,140). Nicotinic activation of intrinsic cardiac neurons evokes a biphasic cardiac response, with initial suppression in regional cardiac function being followed by augmentation (Fig. 6). Nicotinic activation of atrial intrinsic cardiac neurons modifies primarily, but not exclusively, atrial function, whereas nicotinic activation of ventricular intrinsic cardiac neurons modifies primarily, FIGURE 6 Chronotropic and atrial inotropic effects elicited by injecting nicotine into a locus of the dorsal right atrial ganglionated plexus (RAGP) before (control) and following sequential selective muscarinic (atropine) and then -adrenergic (propranolol + atropine) blockade. The dorsal right atrial ganglionated plexus is primarily associated with the control of right...

Health Maintenance And Disease Prevention

Smoking and consumption of alcoholic beverages. But despite the efforts of schools, the government, and other organizational spokespersons to convince people to get a good night's rest, eat breakfast, stop smoking, drink alcohol in moderation (if at all), and exercise, a substantial portion of the population continues to resist those recommendations (see Figure 3-6). The consequence of such an unhealthy lifestyle is pain, disease, and a shortening of the life span.

The holistic approach to management

In a healing profession obsessed with interventionism, invasive technology and drug management, the general practitioner has an obligation to his or her patients to use natural healing methods wherever possible and be very discerning and conservative with investigatory medicine. Patients appreciate natural remedies and taking responsibility for their own management wherever possible and appropriate. Examples include relative rest, exercise, swimming, stress management, meditation, spiritual awareness, antioxidant therapy (e.g. vitamin C, vitamin E, selenium), weight control, optimal healthy nutrition, avoidance of toxins (e.g. illicit drugs, nicotine, caffeine and alcohol) and sexual fulfilment.

Adenoassociated Virus For Immunotherapy

The potential of AAV vectors for cancer immunotherapy is evident from recent studies using cytokine gene transfer and in vivo immunization approaches (108-110). Active immunization with tumor cells transduced with rAAV encoding cytokines either by a plasmid based-delivery system or by a recombinant virus-mediated infection has resulted in regression of tumor growth upon further challenge. In a separate study, high-level IFN-y and elevated major histocompatibility complex (MHC) class I expression was observed following transfer of D122 gene-modified murine lung cancer cells that significantly delayed tumor development (111). Similar findings of antitumor immunity following transfer of cytokine-encoding AAV DNA in a rat prostatic tumor model (112) were reported. Enhancements in antitumor T-cell response was observed in vitro by AAV-mediated transduction of B7.1 and B7.2 genes in a human multiple myeloma cell line (113). In a vaccination scheme, Liu et al. have recently shown that...

Osteopenia Osteoporosis

The following tests should be performed on all patients with AIDS a lumbar spine X-ray in the standard anteroposterior and lateral views, bone density measurement (DEXA scan) of the lumbar spine and hip and laboratory blood tests, including calcium, phosphate and alkaline phosphatase. Osteopenia should be treated with 1000 I.E. vitamin D daily and a calcium-rich diet or calcium tablets with a dose of 1200 mg day. Patients should be advised to exercise and give up alcohol and nicotine. In cases with osteoporosis, aminobiphosphonates should be added. Because testosterone suppresses osteoclasts, hypogonadism should be treated (Cheonis 2002, Cheonis 2000, Mondy 2003, Tebas 2000).

Conclusions And Future Directions

PET provides the opportunity to image multiple dynamic biological processes in situ in brain tumors. Energy metabolism and amino acid transport and incorporation are important components of the pathophysiology of gliomas about which molecular imaging is providing regional biological information that is useful in clinical practice. Imaging hypoxia is straightforward and proliferation imaging with FLT shows significant promise. Neither has been exploited thoroughly enough to allow judgment of their potential benefit to the practice of neuro-oncology. Whereas cell division is the most distinguishing function ofgrowth in tumors, probing membrane biosynthesis with PET and 1- C-11 acetate or a choline tracer may yield information as helpful as protein or DNA synthesis. Because astrocytic gliomas frequently carry epidermal growth factor receptor mutations at a frequency that is related to grade, a PET tracer specific for this mutated receptor could be useful for grading and prognosis (127)....

Neoplastic Conditions

Sinonasal cancer the maxillary sinus is the commonest site for sinonasal malignancy and is usually either squamous cell carcinoma or adenocarcinoma in type. The nasal cavity is the second commonest site and is affected by a broad spectrum of lesions but tumours of the sphenoidal and frontal sinuses are rare. Risk factors include tobacco use, exposure to hard and soft wood dusts, nickel and irradiation.

Other Small Molecule Egfr Inhibitors

Although studies with Iressa are perhaps furthest along, a number of other small molecule inhibitors of EGFR are currently or soon to begin clinical trials in patients with brain tumors. OSI-774 (Erlotinib, Tarceva, Genentech, South San Francisco, CA) exhibits reversible inhibition of EGFR, by competition with the ATP-binding site, similar to ZD1839, with a median inhibitory concentration in the low nanomolar range 132,180 . This agent inhibits EGFR autophosphory-lation at concentrations in the range of 20 nM, and in cell lines dependent on EGFR for proliferation, inhibition of cell growth was observed in a comparable range 180,181 . Higher concentrations were capable of inducing apoptosis. As with ZD1839, this agent induces cell cycle arrest at G1, with accumulation of p27Kip1 182 . In preclinical models, activity has been observed at concentrations in the range of 10 to 200 mg kg day, and early clinical studies confirmed good oral bioavailability. In phase I clinical studies,...

What Is Epidemiology And What Role Can It Play In Urban Health Research

Second, epidemiology plays a critical role in understanding disease etiology, or identifying causes of diseases. Classically, epidemiology has concerned itself with identifying different factors, often called exposures or risk factors that are associated with categorical disease outcomes. Both observational and experimental methods have been employed to this end. Historic examples of this include the identification of smoking as a risk factor for lung cancer and cardiovascular disease and the absence of folic acid as a risk factor for neonatal neural tube defects. In the context of public health practice, epidemiology contributes methods that aid in the search for causes of infectious disease epidemics. For example, outbreak investigations include both the description of the increase in incidence of a particular disease and also the search for the cause, or of the mechanisms of transmission of a well-known cause, of the same disease. Both these traditional roles of epidemiology have...

Historical Significance

In January 2003 a disgruntled grocery worker tainted approximately 200 pounds of ground beef sold at a supermarket in Michigan. At least 92 patients had clinical presentations consistent with nicotine-containing pesticide intoxication. Epidemiology and lab studies confirmed that the food product had been contaminated at the level of the local grocery store, and not at a higher level in the food supply chain. Unintentional contamination with pesticides also has been reported.

Geneticization and BRCA1

Consider, for example, the ways in which biomedicine directs attention primarily to the level of the individual by encouraging each woman to develop high levels of fear about her own risk of contracting breast cancer. In the name of health promotion, women are repeatedly warned of the risk each faces of developing this disease. Many women are easily frightened into a mind-set where they are preoccupied with monitoring their bodies for threatening signs of change (or where they guiltily avoid checking their breasts for fear of discovering some suspicious lump) if a lump is detected, they are primed to quickly seek expert advice and biomedical interventions. This focus on individual responsibility and surveillance occurs as part of a much larger public health campaign aimed at self-regulation not only are women asked to pay worried and regular attention to their breasts, they are also advised to change lifelong eating habits, develop healthy exercise programs, learn stress management...

Aging And Heat Shock Proteins

A characteristic feature of aging is a progressive impairment in the ability to maintain homeostasis in the face of environmental challenges. Heat shock proteins (Hsps) consist of a family of proteins that modulate stresses to the body. Hsps are ubiquitous, highly conserved proteins that have been found in the cells of all organisms studied thus far, including plants, bacteria, yeast, flies, and vertebrates. They are part of a multigene family that has been divided into 6 subfamilies based on molecular size, ranging from 8 to 150 kD (Jaattela 1999). Some are expressed constitutively, whereas others are induced by various types of metabolic or environmental stresses such as heat, ischemia, heavy metal ions, ethanol, nicotine,

Environment as determinant of i genotype and ii disease

Second, the environment presents many exposures that directly alter the probability of occurrence of various diseases. Ionizing radiation contributes to the risks of breast cancer and leukemia. Asbestos causes asbestosis and mesothelioma. Environmental tobacco smoke increases the risks of lung cancer and coronary heart disease. Heavy metals induce various forms of organ dysfunction, for example, environmental lead exposure in early childhood impairs neurocogni-tive development. Patterns of exposure to various antigens in early childhood influence the maturation path of the young immune system, and also

Recommended dosage

Dosages of 0.4-0.6 mg have been used for the treatment of alcohol withdrawal. Total daily dosage for the treatment of opiate withdrawal range between 0.5 and 1.4 mg, depending on the stage as well as the severity of withdrawal symptoms. If the clonidine patch is used to treat nicotine withdrawal symptoms, dosages that deliver 0.1-.2 mg daily are used. For oral therapy (tablets), a total dosage of 0.2-0.4 mg daily is taken in divided doses.

Major Mendelian genes versus minor polygenes as predisposers

Most genetic influences on disease risks, however, occur in polygenic situations where any single contributory gene may shift the probability by no more than a few percentage points. Further, it is likely that it is the interacting set of alleles that is most relevant in determining the level of innate susceptibility of an individual to developing a disorder or disease in response to a particular environmental exposure. In recent years it has become apparent that there are multiple genetic loci which contribute to the occurrence of hypertension, a tendency to rapid weight gain, coronary heart disease, colon cancer, lung cancer and so on. This is hardly surprising. After all, the complex metabolism and physiology of the mammalian organism is, fundamentally, under genetic control, in that all proteins and other active molecules are genetically coded for, and the resultant slight interindividual variations in the molecular structure of proteins affect their biological activity.

Prevention strategies whole populations highrisk groups or selected individuals

That second issue goes further than that. As Rose eloquently pointed out, those factors that best explain the occurrence of cases within a population may not best account for the rate of the disease within the population at large. For example, if the population, overall, consumes a high-fat diet, then whether or not an individual smokes cigarettes may best explain whether he she develops coronary heart disease. Meanwhile, the population-wide dietary behavior may be the main source of the elevated rate of coronary heart disease within that population. Consider another example, admittedly extreme, but it helps to make the point. If within a population everyone smoked 20 cigarettes per day, then the prime determinant of individual risk of lung cancer might well be one or more genetic polymorphisms which determine the fate of inhaled carcinogens. Yet it is the smoking that accounts for the overall high rate of lung cancer in that hapless population.

Other Candidate Genes

Others have examined the possible role of CYP1A1, which is among the major enzymes participating in estrogen hydroxylation, in breast cancer etiology.144-148 Several polymorphisms in CYP1A1 have been described, and two have been associated with breast cancer risk in some,144,146,148 but not all,145,147 studies. The strongest associations for CYP1A1 and breast cancer are limited to women who smoke.

Pharmacodynamics of Darbepoetin Alfa in Patients

Darbepoetin alfa has also been shown to treat anemia in a safe and effective manner in cancer patients receiving chemotherapy. In a multicenter, placebo-controlled study, patients with lung cancer receiving multicycle chemotherapy were randomized to darbepoetin alfa or placebo, and patients who completed the 28-wk study were assessed (126). Patients treated with darbepoetin alfa required fewer transfusions (and had greater Hb responses) than patients receiving placebo. Other studies have suggested that darbepoetin alfa is safe and effective when administered at reduced dosing frequency (once every 1, 2, or 3 wk) (125,127-129). Thus, darbepoetin alfa could be used to treat anemia in patients with reduced-dosing frequency.

How Do We Detect Mutagens

Unfortunately, some chemicals are not recognized to be mutagenic until it is noticed that unusually high numbers of people in a community, a work place, or an occupation are afflicted with rare cancers or have a high number of miscarriages. This was the case with asbestos. We now know that there is no safe level for tiny asbestos fibers that can enter our lungs. It took some time to determine that asbestos was mutagenic because decades passed between exposure and the time when disease symptoms first appeared. Today, asbestos is associated with lung cancer, which is made worse by smoking, and a rare

Neurotoxicantinduced Models Of Parkinsons Disease 6Hydroxydopamine

The 6-OHDA-lesioned rat model has proven to be a valuable tool in evaluating the pharmacological action of new drugs on the dopaminergic system, the mechanisms of motor complications, the neuroplasticity of the basal ganglia in response to nigrostriatal injury, and the safety and efficacy of neuronal transplantation in PD. Extensive pharmacological studies have utilized the 6-OHDA-lesioned rat to investigate the role of various dopamine receptor (D1 through D5) agonists and antagonists, and other neurotransmitter systems (including glutamate, adenosine, nicotine, and opiods) on modulating dopamine neurotransmission. These studies elucidate

Drug Movement Across The Bbb And Determinants Of Cns Drug Concentration

The factors acting to determine the concentrations of drugs and other molecules at a particular location within the CNS are complex. As with other cell membranes, the cerebral endothelium is permeable to low molecular weight (< 500-600 Da), nonpolar, lipid-soluble molecules such as oxygen, carbon dioxide, ethanol, nicotine, diazepam and anesthetics 19,29 . For small molecules, a good correlation exists between the lipophilicity or lipid solubility of a drug (i.e. hydrophobicity), as approximated by the octanol water partition coefficient, and its ability to cross the BBB 2,30,31 . Methotrexate, for instance, has a very low octanol water partition coefficient and penetrates poorly into the brain when given systemically.

Pharmacological treatment

Nicotine replacement therapy, which should be used in conjunction with an educational support program, has been proved to be effective and is available as chewing gum or transdermal patches (the preferred method). Ideally the nicotine should not be used longer than 3 months. Nicotine gum 3 Low dependence (less than 10 cigarettes per day) use non-pharmacological methods rather than replacement Moderate dependence (10-14 cigarettes per day) 2 mg Ensure all the nicotine is utilised. Transdermal nicotine 3 This is available as 16-hour or 24-hour nicotine patches in three different strengths. The patients should stop smoking immediately on use.

Cancer Pain and Chronic Pain

Doctors are beginning to advocate pain relief for all people with cancer who require it, not only for humanitarian reasons but for clinical ones. Studies on rats with lung cancer show that tumors spread more rapidly in animals not given pain medication. Plus, the widespread belief that giving narcotics would addict cancer patients has been shown to be unfounded. Narcotics are much more likely to be addicting when they are taken to provide euphoria than when they are taken to relieve severe pain.

Cancer Prevention

Epidemiological studies have generally shown a decreased occurrence of cancer in those individuals who drink green tea regularly, although this has not been observed in all studies. A 2003 prospective cohort study using 13-year follow-up data found increased green tea consumption was associated with an apparent delay of cancer onset and death, and all cause deaths (Nakachi et al 2003). A phase 2 RCT evaluated the effects of green tea on oxidative DNA damage in 143 heavy smokers over 4 months and found a significant reduction in damage as evaluated from urine and plasma (Hakim et al 2003). A small, controlled, pilot study concluded with similar results when cells from the oral mucosa of smokers showed much less oxidative damage when compared with controls (Schwartz et al 2005). These trials indicate that green tea may be effective in reducing cancer in smokers, but much larger trials are needed. In contrast, a 2001 prospective study in Japan found no association between green tea...

Materials and Methods

Taiwanese HCC patients (308) and healthy controls (304) were recruited from Taipei Municipal Jen-Ai Hospital and Kaohsiung Yuan's General Hospital. Informed consent and peripheral blood (PBL) was obtained from all participants. A questionnaire was designed to collect relevant information regarding HCC risk factors, i.e., age at diagnosis, family history of HCC, hepatitis B virus (HBsAg) or C virus infection (anti-HCV antibody), diabetes mellitus, as well as a-fetoprotein, AST and ALT, and cigarette smoking. The protocols were approved by the Institutional Reviewed Boards, Taipei Veterans General Hospital.

Advantages And Disadvantages Of Observational And Experimental Studies

In this chapter, we've examined both nonexperimental and experimental studies to test various purported health benefits of vitamin C and other antioxidants. Although we've seen that experimental studies have pitfalls, I've emphasized their advantages, which make them the gold standard of medical research for good reason. However, we shouldn't simply dismiss the role of prospective studies, case-control comparisons, and other kinds of nonexperimental designs in medical research. These kinds of studies can provide essential information when experimental studies are impractical or unethical. For example, no one seriously doubts that smok ing has multiple bad consequences for human health, yet much of the evidence for this belief comes from large-scale, long-term comparisons of smokers with matched groups of nonsmokers. In this case, matching subjects for as many potential confounding variables as possible has been a reasonable subst itute for randomly assigning volunteers to smoke or...

Risk Factors for Chemotherapy Induced Febrile Neutropenia

An important and provocative finding in these investigations is the high proportion of overall risk of FN that is present at the beginning of treatment, which is when standard-dose chemotherapy is first given to a previously untreated patient. For years, the treatment paradigm has emphasized the progressive toxicity associated with sequential chemotherapy dosing. Direct and predictable cumulative toxicity for erythroid cells and platelets may occur, but current data suggest that myeloid cells (i.e., neutrophils and monocytes) may show inherently different responses. Careful observation of blood cell counts in patients with small-cell lung cancer (SCLC) treated with up to six cycles of cyclophosphamide, doxorubicin, and etoposide illustrated that neutrophil counts were not progressively lower with each cycle (10). These results suggest that the hematopoietic tissues of the bone marrow adapt to the sequential insults of chemotherapy, just as the bone marrow adapts to produce more...

Antisense Oligonucleotides

Antisense oligonucleotides (ASONs) are a new class of molecularly targeted agents that are transitioning from the laboratory into the clinic. Clinically, these drugs are well-tolerated with favorable toxicity profiles, and laboratory studies have demonstrated that they can be feasibly combined with radiotherapy. ASONs directed against a number of important cellular targets, including the mRNA of c-myb, MDM2, bcl-2, protein kinase C-a, PKA-I, H-ras, c-raf, R1- and R2-subunit of ribonucleotide reductase, and transforming growth factor 2 (105-108) have been investigated in clinical trials. Laboratory studies investigating the potential value of ASONs as radiosensitizers have also been conducted. Survivin is a recently discovered member of the IAP family that plays a dual role in suppressing apoptosis and regulating cell division and interest has been generated on the use of ASONs to target survivin for downregulation (109). A variety of human tumor types including lung, breast, colon,...

Perspectives p53 and cancer management

M., Jamshedur Rahman, S. M. et al. (2003). Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res, 63, 7113-21. Pfeifer, G. P., Denissenko, M. F., Olivier, M. et al. (2002). Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene, 21, 7435-51.

Colony Stimulating Factor Therapy

Abbreviations NHL, non-Hodgkin's lymphoma SCLC, small-cell lung cancer CAE, cyclophosphamide, doxorubicin, and etoposide VAPEC-B, vincristine, etoposide, cyclophosphamide, and bleomycin VNCOP-B, etoposide, procarbazine, cyclophosphamide, vincristine, and bleomycin rHuG-CSF, recombinant human granulocyte colony-stimulating factor. Abbreviations NHL, non-Hodgkin's lymphoma SCLC, small-cell lung cancer CAE, cyclophosphamide, doxorubicin, and etoposide VAPEC-B, vincristine, etoposide, cyclophosphamide, and bleomycin VNCOP-B, etoposide, procarbazine, cyclophosphamide, vincristine, and bleomycin rHuG-CSF, recombinant human granulocyte colony-stimulating factor.

Influence of Some Other Factors on Metal Metabolism and Toxicity

Because sweat is an important route of excretion for some metals (e.g., zinc and nickel), metal losses through sweat might influence metabolism and tox-icity. Workers exposed to nickel in a hot environment had considerably lower nickel levels in blood than expected (Szadkowski et al., 1969). The clearance of inhaled particles from the lung depends on the proper function of the mucociliary transport system. Smoking cigarettes over a long period and bacterial and viral

Ligandbinding Formats

Binding assays for compounds that interact with ligand-gated ion channels are well tailored for HTS and have been used extensively in discovery programs directed toward GABA-, glutamate-, purine-, serotonin-, inositol-1,4,5-triphos-phate-, and nicotine-responsive channels. In addition, voltage-gated ion channels, although lacking endogenous ligand activation, have been studied using binding paradigms. This has been possible where radio- or fluorescence-labeled drugs or toxins bind to the channel at pharmacologically significant sites, such as ligands commonly used for calcium 64 , sodium 65 , and potassium channel proteins 66-71 . Binding methods have also been useful in the study of coagonist and allosteric sites on channel proteins. Examples include the binding of TBPS or TBOB to benzodiazepine sites on GABA receptors 72,73 and ligands for the glycine binding site on NMDA receptors 74,75 . Screening paradigms where the affinity of the radioligand may depend on the state of channel...

Conclusions And Research Directions

Although the U.S. population is generally healthy with good longevity prospects, several factors may hamper future gains. For instance, the increasing prevalence of obesity is an alarming trend and presages increasing mortality from diabetes, heart disease, and some forms of cancer. Further, in the four decades since the U.S. Surgeon General brought to public attention the hazards of cigarette smoking, nearly a quarter of the U.S. adult population continues to smoke, and surprisingly large proportions of individuals start smoking every year. These patterns threaten to offset improving longevity prospects that result from increasing levels of education and public health efforts and are especially pernicious as they disproportionately affect racial and ethnic minorities (U.S. Department of Health and Human Services 2000). There is an opportunity to better understand the social and contextual influences on mortality. Although much work has focused on various social relationships,...

Use Of Csfs For Rbc Support 11 Introduction

Anemia is a common clinical problem in patients with lung cancer. Many patients with lung cancer exhibit anemia at diagnosis that may be aggravated by disease-specific therapy, which is often platinum-based. Many patients with lung cancer are symptomatic (1). In these patients, anemia may cause or aggravate shortness of breath and fatigue. Fatigue is the most often reported symptom in cancer patients receiving chemotherapy and has profound consequences on quality of life (QOL) (2). Anemia can be responsible for delay or reduction of cytotoxic treatment, and it is an independent negative prognostic factor of disease outcome (3,4). The impact of anemia in patients with lung cancer is largely underestimated by the medical community. Despite substantial evidence that treatment of anemia reduces the number of transfusions (and the associated risks) and improves QOL, many clinicians still only treat with red blood cell (RBC) transfusions if their patients' hemoglobin (Hb) concentration...

Causes of Anemia in Patients

Anemia in patients with lung cancer has a multifactorial etiology (6). Contributing factors are the anemia of chronic disorders, concomitant postobstructive respiratory infections, tumor-induced autoimmune hemolysis, and bone marrow invasion or dysfunction caused by the tumor. These patients can also have iron, folate, or vitamin B12 deficiency, as well as blood loss from tumor erosion. Endogenous EPO is of particular interest, since anemic cancer patients have been shown to have inappropriately low amounts of circulating EPO for their degree of anemia, reflecting a perturbation in this homeostatic mechanism, with loss of the normally expected inverse linear relation between serum EPO and Hb concentrations (7,8). In a study with a very homogenous group of chemotherapy- and radiotherapy-naive patients with lung cancer, analysis of serum EPO and soluble transferrin receptor suggested that impaired erythroid marrow response to EPO and a relative inadequacy of EPO production were...

Incidence of Anemia in Patients

The prevalence of pretreatment anemia varies across different solid tumor types. In an anemia audit, up to 60 of patients with lung cancer had Hb values < 11 g dL, a considerably higher prevalence than in patients with colorectal or breast cancer (10-20 ). Consequently, approx 40 of patients with lung cancer needed blood transfusions, compared with only about 20 of patients with breast cancer (16). The proportion of patients with anemia increases over the course of treatment. The problem of anemia in patients undergoing chemotherapy has been reviewed for NSCLC (17) and for cancer in general (18). A larger variation in both mild-to-moderate anemia (Hb concentration > 8.0 g dL) in 8-100 of patients with lung cancer and severe anemia (Hb concentration < 8.0 g dL) in 0-55 was reported. In a retrospective analysis including 128 patients with lung cancer, chemotherapy significantly decreased Hb concentrations compared with pretreatment values, with a significantly more prominent...

Effect of Anemia on Disease Outcome

A Hb concentration > 11.0 g dL was a significantly (p 0.001) favorable prognostic factor in a large retrospective analysis of 2531 patients with advanced NSCLC (67). The relationship between anemia and survival was examined in a review of 60 papers, 25 of which were about lung cancer (3). The relative risk of death of anemic patients with lung cancer increases by 19 (95 confidence interval (CI) 10-29). This effect is present regardless of whether the patients are treated with chemotherapy, radiotherapy, or surgery (4). An important additional question is whether this effect is because the lower Hb values are a sign of more advanced disease, or whether the anemia compromises anticancer treatment and thereby survival. In the last scenario, treatment of anemia might improve disease control and outcome. Several theoretical arguments (the role of tumor hypoxia in resistance to therapy 68 ) and patient data, in the fields of both radiotherapy (especially for head-and-neck and gynecologic...

Recommendations for the Use of Erythropoietic Factors

Anemia is a problem in up to 50-60 of patients with lung cancer, especially if they are treated with platinum-based chemotherapy. Despite its well-documented profound impact on QOL, many clinicians only treat with transfusion, once severe anemia (Hb concentration < 8 g dL) is present. Much evidence supports the use of rHuEPO for chemotherapy-induced anemia, if the Hb concentration decreases by < 10 g dL (79). Although recent data suggest that QOL may be preserved better if rHuEPO is started when the Hb concentration is < 12 g dL, there is at present not enough evidence to make an overall recommendation for this strategy, but rather clinical evidence in particular circumstances. include reduced time missed from work for physician visits and potentially better patient compliance. In a large randomized, placebo-controlled, phase 3 study in patients with lung cancer, using an administrations schedule of 2.25 g kg once weekly, darbepoetin alfa showed a statistically significant and...

Use Of Csfs For Wbc Support

Neutropenia is a common side effect of chemotherapy for lung cancer. Neutropenia can be associated with febrile neutropenia (FN), neutropenic sepsis, which may be life-threatening, prolonged hospital admission for administration of iv antibiotics, and increased cost. Grade and duration of neutropenia have been correlated with the risk of developing sepsis. This section reviews the use of rHuG-CSF or rHuGM-CSF in lung cancer in these different settings, based on published randomized data. Finally, some guidelines for the use of white blood cell (WBC)-stimulating cytokines in the clinical approach to patients with lung cancer are given.

Recommendations for the Use of White Blood Cell CSFs 231 Primary Administration

Ommend reserving primary administration of CSF for patients with an expected incidence rate of FN of at least 40 (112). Thus, for most standard chemotherapy regimens for patients with lung cancer, primary administration of CSF is not recommended. Guidelines, however, recognize that there are some clinical situations in which the use of CSF might be appropriate, as in the case of patients at high risk for postobstructive pneumonia, with extensive prior chemotherapy and or irradiation, with a history of recurrent FN while receiving earlier chemotherapy, or with decreased immune function. The recommended dose is 5 g kg per day for rHuG-CSF (filgrastim) and 250 g m2 per day for rHuGM-CSF (sargramostim), to be started between 24 and 72 h after chemotherapy until the occurrence of a neutrophil count of 10 x 109 L. CSFs should be avoided in patients receiving concomitant chemoradiation. Although some limited evidence exists that CSFs can decrease the probability of FN in subsequent cycles of...

Environmental factors

Failed to identify the major causative factor(s). Many environmental factors have been proposed as causative agents for IBD (Table 20.1). From these, diet, domestic hygiene and micro-organisms were the most investigated areas (Andersson et al., 2001 Bull et al., 2003 Cosnes et al., 1999 Darfeuille-Michaud et al., 1998 Ekbom et al., 1990 Ekbom et al., 1996 Gent et al., 1994 Gilat et al., 1987 Godet et al., 1995 Greenstein, 2003 Kallinowski et al., 1998 Lamps et al., 2003 Persson etal., 1987 Sanderson etal., 1992 Thompson etal., 1995). In fact the only risk factors that can be currently supported are appendectomy, which has a protective role in UC, and tobacco. Smoking protects against UC (OR 0.41 (0.34-0.48) and improves the disease course (Calkins, 1989). On the other hand, smoking increases the risk of CD (OR 2.0 (1.65-2.47)) and the severity of the disease, as shown by an increased use of immu-nosuppressant agents and surgical intervention in smokers (Calkins, 1989 Cosnes et al.,...

Empirical Support Of Relationalcultural Theory

Data from empirical research increasingly supports the power of connection to protect and to heal. The literature on resilience shows that a connection with one adult (parent or teacher) is the single best protection against high-risk behaviors of drinking, violence, depression, and suicide in adolescents (Resnick et al., 1997). Students who felt connected were less likely to use cigarettes, alcohol, or drugs less likely to engage in early sexual activity, violence, or become pregnant and less likely to experience emotional distress. These studies do not point to personality traits or diagnostic categories as the best predictors of outcome they clearly and strongly point to the centrality of connection.

Approaches to Exposure Assessment

Questionnaires used for exposure assessment generally cover sources of exposure, e.g., presence of cigarette smoking or pets, and time-activity in general, people cannot accurately classify the intensity of an exposure. Information on concentrations at which exposures are taking place can be gained with use of personal monitors for airborne contaminants or of microenvironmental modeling. Concentrations of contaminants in water supplies can be directly measured and combined with information on quantities consumed to estimate dose.

Clinical Manifestations

Another manifestation of LCH is primary pulmonary LCH, which affects both children and adults. Pulmonary LCH has been associated with cigarette smoking in adults, and the course tends to be severe. The childhood form of pulmonary LCH appears to be less severe but more chronic in nature (6).

Granulocyte Colonystimulating Factor And Granulocytemacrophage Colonystimulating Factor For Chemotherapyinduced

Crawford et al. (19) did a randomized, double-blind, placebo-controlled trial in patients with small-cell lung cancer (SCLC) to evaluate the incidence of fever and neutropenia in patients treated with chemotherapy. Two-hundred eleven patients receiving chemotherapy with cyclophosphamide, doxorubicin, and etoposide (CAE)

Protein Tyrosine Kinase Inhibitors

The role of EGFR in many cancers was appreciated early on and was one of the first targets for therapy. Indeed, the quinazoline Iressa (ZD 1839) (Fig. 3) 21,25 is in advanced clinical trials for treatment of cancers for which EGFR plays an important role, such as lung cancer and head and neck cancer. Similarly, the quinazoline AG 1478 (Fig. 3) 22 is in clinical development for the treatment of glioblastoma multiforme in which the EGFR and its persistently active A (2-7) EGFR are overexpressed 30,31 . This tyrphostin will be used in combination with CDDP, with which it synergizes to induce apop-tosis in glioma multiforme cells in vitro and in vivo 31 . OSI 774 (Fig. 3) is also an effective quinazoline in clinical development 32 . Over the years, we have come to realize that het-erodimer combinations of the four members of the Her family play a role in the oncogenic phenotype of many cancers therefore, attempts are being made to generate inhibitors that inhibit both Her-1 and Her-2. The...

Cost Effectiveness Analysis

Cost effectiveness analysis typically expresses the tradeoff between the costs of an intervention to the non-financial outcomes as a ratio. Cost effectiveness analysis is concerned with what is happening at the margins - that is, an accounting of the additional, or incremental, costs and effects of an intervention. Cost effectiveness analysis can inform health care decision making by indicating which of several alternative demands for health care spending can improve health the most. For example, consider a city public health official who must decide between expanding one of three programs - smoking cessation, safe sex counseling, or food inspection -within a fixed budget. CEA can indicate which of the three programs will be associated with the greatest improvement in health effects. These health effects could be measured as life years gained, hospitalizations averted, improvements in quality of life scores, or many other metrics. Real world decision making can highlight the...

Genetic abnormalities downstream of notch signal activation

Disorders in the general population as well as in cancer patients (Nijziel et al., 1999 Paspatis et al., 2000). Other factors such as the endothelial cell protein C receptor and thrombomodulin have been implicated in the functioning of protein C. Both the protein C receptor and thrombomodulin are expressed frequently in cancer cell lines and in breast cancer (Tsuneyoshi et al., 2001). a-1-antitrypsin was shown many years ago to possess immunosuppressive properties, besides being associated with certain human neoplasms as a paraneoplastic marker. It was even suggested to relate to the state of progression of carcinoma of the cervix (Sherbet, 1982). Recent work indicates a link-up between a-1-antitrypsin deficiency with genetic instability. For instance, a fifth of colonic carcinomas with high microsatellite instability were deficient in a-1 antitrypsin. In contrast, colonic tumours with low microsatellite instability were comparable with a control group in respect of antitrypsin...

Peripheral Vascular Disease

Chronic ischemia is by far the most common symptom of peripheral vascular disease, and with proper attention most patients will not progress to surgery. Patients with chronic ischemia due to peripheral vascular disease are at a higher risk of death from all vascular causes. Theses patient should receive full anti-atherosclerotic therapy, including help with smoking cessation and anti-lipid therapy. Smoking is the major risk factor for peripheral vascular disease and its progression. The other effective therapy is a supervised exercise program. Patient who follow such a program will have improvement of their exercise performance and a prolonged pain-free walking distance.

Dihydrochelirubine 12monooxygenase

The intense interest in this and related enzyme activities is consequential to the central role that 3,4-benzpyrene plays in the aetiology of human lung cancer. In man and rat, liver enzyme is primarily microsomal, and is activated by low molecular weight cofactors. In man, the activity is twice as high in smokers compared with non-smokers. In rat, activity is three times higher in males than in

Michael J Spivey Daniel C Richardson and Monica Gonzalez Marquez

In another headband-mounted eyetracking experiment, Spivey and Geng (2001, Experiment 1 see also Spivey, Tyler, Richardson, & Young, 2000) recorded participants' eye movements while they listened to spoken descriptions of spatiotemporally dynamic scenes and faced a large white projection screen that took up most of their visual field. For example, Imagine that you are standing across the street from a 40 story apartment building. At the bottom there is a doorman in blue. On the 10th floor, a woman is hanging her laundry out the window. On the 29th floor, two kids are sitting on the fire escape smoking cigarettes. On the very top floor, two people are screaming. While listening to the italicized portion of this passage, participants made reliably more upward saccades than in any other direction. Corresponding biases in spontaneous saccade directions were also observed for a downward story, as well as for leftward and rightward stories. (A control story, describing a view through a...

Animal Models and Insights into Mechanisms of Lung Senescence

Another important factor important in lung aging may be the ability of homeostatic mechanisms to maintain the integrity of the lung microvasculature and alveolar wall capillary bed. Vascular endothelial cell growth factor (VEGF) appears to be an extremely important gene product for the development and maintenance of the lung vasculature (Berse et al., 1992 Monacci et al., 1993 Zeng et al., 1998), and recent studies have shown that emphysema in smokers is associated with a reduction in VEGF expression (Kasahara et al., 2001 Koyama et al., 2002 Kanazawa et al., 2003a Kanazawa et al., 2003b). Blockade of VEGF receptors in a rat model has been shown to correlate with induction of epithelial cell apoptosis and cause distal airspace enlargement (Kasahara et al., 2000). However, this change was prevented by the administration of a caspase inhibitor, which suggests that if VEGF production by epithelial cells and VEGF signaling is not disrupted, emphysematous changes do not occur. These...

Principal Metals Showing Mutagenic Effects

Metals, such as nickel compounds and chromate, are associated with exposure to other environmental carcinogens such as cigarette smoking (Gibb et al., 2000 Grimsrud et al., 2002b 2003). Recent success in inducing cancers with arsenite and chromate in mice was associated with the use of hairless mice exposed to both UV and these carcinogenic metals through their drinking water (Davidson et al., 2004 Ross-man et al., 2001 2004). Thus, in general, carcinogenic metals have strong interactions with carcinogens, such as PAH, UV, and the many carcinogens that are present in cigarette smoke. Some carcinogenic metals such as nickel compounds are able to induce cancers in animals exposed to these metals alone, although nickel also has a strong interaction with other organic carcinogens such as benzo(a)pyrene and UV (Schwerdtle et al., 2002 Waalkes et al., 2004 Wozniak and Blasiak, 2004).

Combining Viral Oncolysis With Delivery ofAnticancer Genes

Synergy with chemotherapeutic agents has also been described for HSV. The oncolytic effect of HSV-1716 in combination with mitomycin was synergistic in two of five nonsmall cell lung cancer cell lines in vitro and inhibited tumor growth more efficiently than either agent alone (77). Combination treatment of the HSV mutant G207 and vincristine led to strongly enhanced in vitro cytotoxicity without affecting infection efficiency and replication of G207 in rhabdomyosarcoma cells. In vivo combination treatment of alveolar rhabdomyosar-coma using intravenous G207 and vincristine resulted in complete tumor regression without evidence of regrowth in five of eight animals whereas none of the animals receiving either monotherapy were cured (78).

The Basic Legal Tools

These three different approaches can be illustrated with a simple example. Consider, for example, the public health problem of smoking. One approach is to regulate smoking directly, by prohibiting smoking in particular places and by particular people, i.e., children. A second approach is to provide economic incentives either for individuals to encourage them not to smoke, for example, by raising the price of cigarettes through taxes, or for businesses to encourage them to ban smoking or to offer smoking cessation programs. The third approach is for government itself to provide smoking cessation programs, public information about the harms of smoking, and to ban smoking in government buildings and facilities. These legal techniques vary in their infringement upon individual autonomy and may also vary with respect to cost and effectiveness, but all three are used in connection with urban policy. Each of these approaches is explored below.

Reproductive biology

Once in possession of a cavity, sturnids typically construct a bulky nest of grasses, leaves, fine twigs, and other materials. Sometimes these include man-made objects, and there have been cases of European starlings adding discarded, but lighted, cigarettes to a nest with disastrous results. The amount of material added tends to be whatever it takes to fill the cavity. Red-

Chronic obstructive pulmonary disease COPD

COPD is defined as airflow obstruction that does not vary significantly over time. It is a heterogeneous disease which may develop from destruction of the lung parenchyma (emphysema) or inflammation of the small airways (bronchiolitis). In any affected individual there may be considerable overlap, with each of these components contributing a varying amount to airflow obstruction. Chronic bronchitis is defined by the presence of cough with sputum production that is present for three or more months of the year, for at least two consecutive years. The most common cause of COPD is cigarette smoking (Anderson and Ferris, 1962 Fletcher and Peto, 1977 Surgeon General, 1979). Although chronic bronchitis is associated with cigarette smoking, and is often present in patients with COPD, it is not synonymous with COPD. The terms should not be used interchangeably as chronic bronchitis may occur in the absence of airflow obstruction. airflow obstruction. Moreover, in long standing asthma there may...

Environmental risk factors for the development of COPD smoking

COPD is a major cause of global morbidity and mortality. An estimated 44 million people suffered from COPD in 1990 (Wise, 1997) and this condition accounts for approximately 2.8 million deaths year. COPD is currently the fifth most common cause of death worldwide. However with the increase in the prevalence of smoking in the developing world (Peto et al., 1999), it is predicted to become the third most common cause of death by 2020. The most important environmental risk factor for the development of COPD is cigarette smoking. Cross-sectional population studies have shown that smokers have poorer lung function (lower FEVJ and a greater rate of decline in FEV1 than non-smokers (Dockery et al., 1988 Fletcher and Peto, 1977 Prescott et al., 1997). However it remains unknown why only 15 20 of smokers develop significant airflow obstruction. One explanation is the variation in pack years smoked (one pack year is 20 cigarettes day for one year), with heavy smokers being at significantly...

Genetic risk factors for the development of COPD

The observation that only a minority of cigarette smokers develop COPD suggests that additional factors contribute to the impact of smoking on the development of chronic airflow obstruction. The most important genetic factor in the development of COPD is the Z allele of -antitrypsin. Alpha -antitrypsin is the most abundant circulating proteinase inhibitor and plays a central role in protecting the lungs against proteolytic attack. The Z allele (GZu342Lys) results in 85 of the synthesized mutant -antitrypsin being retained as polymers within hepatocytes (Lomas et al., 1992). This results in plasma levels of -antitrypsin that are only 10 15 of the normal M allele. Homozygotes for the Z allele are greatly predisposed to developing emphysema if they smoke (Piitulainen and Eriksson, 1999). However severe Z -antitrypsin deficiency makes up only 1 2 of all cases of COPD and there is considerable variability in FEVi between current and ex-smokers with the same PI Z genotype (Silverman et al.,...

Substance abuse and related disorders

Substance-related disorders are disorders of intoxication, dependence, abuse, and substance withdrawal caused by various substances, both legal and illegal. These substances include alcohol, amphetamines, caffeine, inhalants, nicotine, prescription medications that may be abused (such as sedatives), opioids (morphine, heroin), marijuana (cannabis), cocaine, hallucinogens, and phencyclidine (PCP). According to the mental health clinician's handbook, Diagnostic and Statistical Manual of Mental Disorders (the DSM), fourth edition text revised (DSM-IV-TR), all of the substances listed above, with the exceptions of nicotine and caffeine, have disorders of two types substance use disorders and substance-induced disorders. Substance use disorders include abuse and dependence. Substance-induced disorders include intoxication, withdrawal, and various mental states (dementia, psychosis, anxiety, mood disorder, etc.) that the substance induces when it is used. The DSM-IV-TR does not recognize...

Diseases Laws And Social Constructs

How, then, have 'addictions' come to be conceptualised within a disease framework, while lacking such a central feature, and when the main 'symptom' is an integrated goal-directed series of actions (i.e. to obtain more supplies) rather than some incapacity or deficit (It should be noted that intoxication is not a required component of 'addiction'. The fact that some drugs can disrupt behaviour is irrelevant to definitions of 'addiction'. Thus being 'drunk' is not the same as being an 'alcoholic'. So-called addiction to nicotine, on the other hand, produces neither intoxication nor intoxication-related performance deficit, but may even improve performance on certain tasks. The answer lies in the history of the word itself and the observation that the term 'addiction' was originally a socially functional label rather than a scientifically derived concept. Its purpose was to change the public attitude towards the problems of substance abuse away from one of moral censure and 'disease of...

Measured or modelled compounds

Ofnitrogen oxides and sulfur dioxide from industry and from heating and traffic sources were estimated, using a combination of models and monitoring data. Controlling for age, smoking habits and length of education, the adjusted risk ratio for developing lung cancer was 1.08 (95 CI 1.02-1.15) per 10-pg m3 increase in average concentration of nitrogen oxides at a home address between 1974 and 1978. The corresponding figure per 10-pg m3 increase in sulfur dioxide was 1.01 (95 CI 0.94-1.08).

Immunization with Tumor Antigens

The availability of identified tumor antigens for lung cancers has made it possible to immunize patients directly against these antigens. The earliest studies used TAAs derived from cell membranes of various tumors. These had been found to induce antibody responses. In a phase III study of resected (stage I II) squamous cell carcinoma, patients were randomized to TAAs emulsified with complete Freund's adjuvant (CFA), CFA alone, or no immunization. The median and 5-yr survival of the TAA group (106 mo and 75 ) exceeded the CFA alone (71 mo and 53 ), and no immunotherapy (34 and 38 mo) groups (57). Because these were relatively crude preparations, regulatory considerations have driven the switch toward the use of more purified epitopes delivered either in adjuvant or presented by dendritic cells (DCs). In one clinical trial, HLA-A2+ patients with NSCLC and tumor expression of NY-ESO-1 were given eight weekly intradermal injections of NY-ESO-1 peptides 157-165 and 157-167 with GM-CSF as...

Animal Modeling In The Postgenomics

Once a putative therapeutic has been identified, careful consideration is again required for the disease model and the endpoints to be measured. In most cases, targets will arise out of the clinical epidemiology of a specific disease, but for in vivo testing, it is not sufficient to just seek out models of the underlying disease without regard for the specific molecular target of interest. For example, testing of EGFR inhibitors should utilize not just any lung cancer model, but specifically lung cancer models where the tumor is driven by mutated EGFR. In the case of xenografts or syngeneic tumor transplants, it will be critical to fully characterize the cell lines and verify that they at least express the target of interest. In the case of GEM, tumor cells derived from GEM, or engineered human cells, it is likewise important to establish that the model is driven by the target of interest.

Effect of Two Easily Applied Rules in the Adjuvant and Advanced Disease Setting

To illustrate this, suppose one had designed a trial to test the hypothesis H0 5 0 versus 5 > 0 to have 90 power versus the alternative HA 5 ln(1.5) with a one-sided a of 0.025, using a Fleming et al. (10) rule with three interim looks. Such a design would require interim looks when there had been 66,132, and 198 events, with final analysis at 264 events. From Table 1a of Fleming et al. (10), one such rule would be to stop and conclude that the treatment was beneficial if the standardized logrank statistic Z exceeded 2.81 at the first look, 2.74 at the second look, or 2.67 at the third look. The null hypothesis would be rejected at the end of the trial if Z exceeded 2.02. If a symmetric lower boundary were considered inappropriate, one might choose to replace it by simply testing the alternate hypothesis HA 5 ln(1.5) versus 5 < ln(1.5) at some small significance level (e.g., a 0.005) at each interim look (this suggestion is adapted from the monitoring rules in SWOG Protocol...

Identify Public Health Needs and Affected Populations

As an example of how data can inform the establishment of public health priorities, consider New York City mortality data. Cardiovascular disease, followed by cancer, are the city's leading killers, accounting for, respectively, 41.1 and 23.0 of all deaths in 2002. Many of these deaths can be directly attributed to cigarette smoking, which kills approximately 10,000 New Yorkers per year, making it the leading preventable cause of death. A further examination of these mortality data reveals, for example, that for both heart disease and colon cancer, black New Yorkers die at younger ages than white New Yorkers (Figure 1, Figure 2), which may indicate missed opportunities for prevention, early detection and treatment among blacks. Similar patterns can be detected when examining another leading cause of death among New Yorkers - HIV AIDS. While mortality rates have been declining over time, differences among racial ethnic and income groups exist

Clinical efficacy Lifestyle modifications

Several modifications of habits are recommended for patients with GERD. These include rising of the head of the bed, early evening meals with sufficient time to elapse before going to bed, weight reduction, stopping smoking and avoidance of alcoholic beverages etc (for overview, see 22 ). None of these measures have been studied with sufficient quality so far. Therefore, its merits - if there are any - cannot be evaluated based employing the methods of evidence-based medicine. Certainly, some suggestions may have some limited value in an individual patient. It seems, however, questionable to recommend these lifestyle modifications as a prerequisite for starting effective drug therapy. It is completely unknown whether life style modifications have any effect as an adjunct to effective drug therapy.

Case Reports of Toxicity Caused By Commercially Available Products or Traditional Uses by Various Specialty Populations

One case of an acute lateral wall myocardial infarction (MI) was reported in a woman after daily ingestion of Edita's Skinny Pill (containing 300 mg bitter orange plus caffeine and guarana) for 1 year (44). The 55-year-old Caucasian woman developed chest discomfort after eating Chinese food. After workup at the hospital, the woman was diagnosed with acute lateral-wall MI and smoking addiction. Her ejection fraction was 0.45. Prior to this incident, she had no known coronary artery disease, hypertension, or hyperlipidemia.

Promote Evidence Based Interventions

Tackling priority health concerns requires an appreciation of the conditions that underlie them. For example, an examination of actual causes of death, i.e., external, modifiable factors that contribute to death, reveals that, in 2000, approximately half of all deaths in the U.S. could be attributed to largely preventable behaviors and exposures heading the list were tobacco and poor diet physical inactivity, accounting for 18.1 and 16.6 of all deaths nationwide, respectively (Mokdad, et al., 2004). Thus, if the public health community hopes to have an impact on preventable deaths, effective interventions to address tobacco use, physical inactivity and poor diet are needed.

The Economics of Health Care

Health care costs have risen steadily and now exceed US 1 trillion annually, including nearly US 150 billion for cancer care (1,2). By the year 2010, it is projected that health care expenditures in the United States will approach US 3 trillion with US 300 billion spent on cancer care (Fig. 1) (3). Approximately 90 of medical costs for cancer care are associated with five diagnoses breast cancer (24 ), colorectal cancer (24 ), lung cancer (18 ), prostate cancer (18 ), and bladder cancer (8 ) (4,5). Hospital care represents the largest single cost component, accounting for 40-50 of total cancer care costs (2). Other major components of health care costs include physician professional costs and to a lesser extent pharmaceutical and home care costs. The direct medical costs of cancer care are greatest during the period of initial diagnosis and treatment (6). Other illness-related costs in patients with cancer include direct

MDA7 is a Tumor Selective Apoptosis Inducing Factor

The initial observation of mda-7 loss of expression in melanomas and its correlation with progression of this type of tumors suggested growth suppressive properties in melanoma cells (4-7). Ensuing studies investigated the effects of ectopic expression of mda-7 in a wide variety of tumor cells (melanoma, carcinomas of the breast, colon, prostate, nasopharynx, high grade gliomas, and osteosarcoma) and proved that mda-7 inhibits tumor cell growth regardless of the status of other genes (p53, Rb, Bax or p16) (1,9,10) (see Fig. 2 for a representative study of lung cancer cells). However, expression of the gene in normal human skin fibroblasts and mammary breast epithelial cells did not significantly affect their growth or trigger apoptosis (9,10). Together, these reports indicate that MDA-7 is an IL-10 family cytokine with tumor cell apoptotic activity and that the cytotoxic effects it induces are specific to tumor cells (5,10,22-24). Several studies have investigated the signal...

Antimetastatic Activity Of Mda7il24

In vitro, MDA-7 expression resulted in significant inhibition of migration (see Fig. 7B) and invasion of tumor cells plated on Matrigel coated wells (21,71). This inhibitory effect was independent of the previously established cytotoxic effects of MDA-7 on tumor cells and occurred by down regulating p85 PI3K, pFAK, MMP-2, and MMP-9 expression (71). A role for these signaling molecules and proteolytic enzymes in tumor metastasis and angiogenesis has previously been reported (62). For example, involvement of MMPs in invasion and angiogenesis in lung cancer has been demonstrated by the expression of MMP-2, -9 in several lung cancer cell lines and surgical specimens, their localization to the tumor neovasculature, and a correlation between MMP expression and prognosis. Inhibition of tumor metastasis by MDA-7 IL-24 was also demonstrated in vivo (71,77). Intravenous injection of lung tumor cells treated with Ad-mda7 ex vivo into nude mice resulted in reduced number of lung tumor metastasis...

Strategies Directed at the School Setting

The school setting offers the only ready opportunity for sustained direct contact with young people in large numbers. In 2002, projected enrollment in U.S. elementary and secondary schools stood at over 53 million in more than 120,000 schools. For 13 years, between the ages of 5 and 17, students spend six hours per day, five days per week in school for some 40 weeks each year, providing a setting for ongoing, incremental intervention. Although young people are generally healthy, these are years when many key health-related habits of adult life are established (Grunbaum, et al., 2004). By modifying the pattern of risk factors that underlie chronic disease (mainly tobacco use, physical inactivity and nutritional habits) and other causes of premature mortality (risky sexual behavior, violence), subsequent injury and ill health can be averted (Kolbe, 2004).

Risk Factor Surveillance and Medical Room Utilization

The CDC Youth Risk Behavioral Surveillance System (YRBSS), established in 1990 and conducted biannually, measures the high school (grades 9-12) prevalence of risk behavior in six key areas intentional and unintentional injury, tobacco use, alcohol and other drug use, sexual activity, diet and physical activity. Surveys typically permit citywide estimates and analysis by gender and race ethnicity, but sample sizes are too small to examine by geographic area within cities, which may be important for local planning. A modest increase in financial support to increase the sample size permitted calculation of New York City borough-specific estimates (Fornek, et al., 2004). The DOHMH also conducted a special survey of heights and weights among elementary students that highlighted the extent and magnitude of obesity and overweight (Thorpe, et al., 2004).

Strategies Directed at the Policy Environment

Increasing the unit price of cigarettes both reduces smoking initiation and increases cessation (Task Force on Community Preventive Services, 2001). The DOHMH had long advocated for excise tax increases, and in 2002, the tobacco excise tax in New York City rose twice. First, New York State raised its excise tax from 1.11 to 1.50 per pack, followed by an increase in New York City's excise tax from 0.08 to 1.50 - resulting in a combined tax of 3.00 and a pack price ranging from 7.00 to 7.50 - at the time, the highest price in the nation. Smoke-free air or clean indoor air legislation has been shown effective in reducing exposure to secondhand smoke and encouraging smokers to quit (Task Force on Community Preventive Services, 2001). In 1995, New York City enacted clean air legislation that prohibited smoking in many workplaces and public areas, including larger restaurants. However, this bill exempted bars and small restaurants, and allowed designated smoking areas in many...

The Efficacy of Prophylactic Colony Stimulating Factors

Several studies of the efficacy of CSF for prevention of neutropenic complications and the infection risk associated with cancer chemotherapy in a variety of malignancies using different chemotherapy regimens have been reported (65-72). Controlled clinical trials conducted in both Europe and the United States have shown the ability of rHuG-CSF (filgrastim) to reduce the risk of FN associated with systemic chemotherapy in selected patients when it is administered prophylactically before the onset of fever or neutropenia. In the initial clinical trial, Crawford et al. (65) randomized patients with small-cell lung cancer (SCLC) in a prospective, double-blind, placebo-controlled trial of rHuG-CSF after treatment with cyclophosphamide, doxorubicin, and etoposide (CAE). During the first cycle of treatment, when all patients were in the double-blind portion of the trial, 27 of filgrastim patients experienced FN compared with 55 of placebo patients (p < 0.001). One or more episodes of FN...

Biology And Molecular Genetics

The metastatic phenotype is the result of a complex alteration of gene expression that affects tumor cell adhesion, motility, protease activity, and internal signaling pathways 33,34 . Initial changes involve down regulation of surface adhesion molecules, such as integrins and cadherins, which reduces cell-to-cell interactions and allows easier mobility through the surrounding extracellular matrix (ECM). Cell motility is also accelerated in response to specific ligands, such as scatter factor and autocrine motility factor 32-34 . Several oncogenes and signal transduction pathways are also commonly activated in these aggressive cells, including members of the Ras family, Src, Met, and downstream molecules such as Raf, MAPK 1 2, Rac Rho, PI3-kinase, and focal adhesion kinase. Cellular invasive capacity is augmented in the metastatic phenotype by increased tumor cell secretion of matrix metalloproteinases (e.g., collagenases, gelati-nases, elastases) and other enzymes that degrade the...

CT Study Example of Detection Accuracy

The detection of abnormal lymphoid tissue is an important aspect of chest imaging. This is true especially for the mediastinum, the central portion of the chest that contains the heart, major blood vessels, and other structures. Abnormally enlarged lymph nodes, or lymphadenopathy, in the mediastinum can be caused by primary malignancy such as lymphoma, metastatic disease that results from the spread of breast or lung cancer through the lymphatics, tuberculosis, or non-infectious inflammatory diseases such as sarcoidosis. Typically radiologists can easily locate lymph nodes in a chest scan. The detection task is therefore to determine which of the located lymph nodes are enlarged.

Traditional Chemotherapeutic Approaches

The most common approach to chemotherapy for brain metastases is to administer it ''up front'', before or during conventional RT or radiosurgery 42-51 . Several authors have demonstrated that combination regimens given intravenously can be active in this context (see Table 35.1). The most frequently used agents included cisplatin, etoposide, and cyclophos-phamide (CTX). In a series of 19 patients with small-cell lung cancer and brain metastases, Twelves and co-workers used intravenous (IV) CTX, vincristine, and etoposide (days 1-3) every three weeks before any form of irradiation 42 . Ten of the 19 patients (53 per cent) had a radiological or clinical response. In 9 patients, there was CT evidence of tumor shrinkage (1 CR, 8 PR) while in 1 patient there was neurological improvement, without neuro-imaging follow-up. The mean time to progression (TTP) was 22 weeks, with a median overall survival of 28 weeks.

Interstitial Chemotherapy

Tolerated, similar to the experience with gliomas, with adverse events in only 7 patients (e.g., seizures, eye pain, re-operation for cerebral edema). No local recurrences were noted in the cohort there have been 4 remote CNS failures. The median survival in follow-up of 16 evaluable patients was 15.5 months. The authors concluded that the BCNU wafer was well tolerated and active against MBT and should be tested in a phase III trial. In a recent report of 42 consecutive patients with MBT, Brem and colleagues described their experience with the implantable BCNU wafers 97 . Thirty-four patients were newly diagnosed, while 8 were treated at recurrence. Radiotherapy (3000-4400 cGy) was used, in addition to surgical resection and wafer placement, for all newly diagnosed patients. The majority of the cohort had MBT from non-small-cell lung cancer (20), melanoma (11), renal carcinoma (4), and breast (3). There were no localized recurrences in newly diagnosed patients 3 patients developed...

Molecular Treatment Approaches

Gefitinib (ZD 1839, Iressa) is another protein tyrosine kinase inhibitor with selective activity against EGFR 105-107 . It has been clinically effective against several different types of solid tumors, including non-small-cell lung cancer and brain tumors. Several authors have recently described case reports of the use of gefitinib in patients with MBT from non-small-cell lung cancer 120-124 . Several of these initial patients had objective responses, including a few CR, that were quite durable. These early reports lead Ceresoli and colleagues to perform a prospective phase II trial of gefitinib in patients with non-small-cell lung cancer 125 . Forty-one consecutive patients were treated with gefitinib (250 mg day) 37 had received prior chemotherapy and 18 had undergone brain irradiation. There were four patients with a PR and seven with SD. The overall progression-free survival was 3 months. However, the median duration of responses in the patients with a PR was 13.5 months.

Overview And Future Considerations

Treatment of brain metastases from lung cancer chemotherapy. Lung Cancer 45(suppl 2), S253-S257. 36. Milas, I., Komaki, R., Hachiya, T. et a . (2003). Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases. C in Cancer Res 9, 1070-1076. 42. Twelves, C. J., Souhami, R. L., Harper, P. G. et a . (1990). The response of cerebral metastases in small cell lung cancer to systemic chemotherapy. Br J Cancer 61, 147-150. 45. Bernardo, G., Cuzzoni, Q., Strada, M. R. et a . (2002). First-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain metastases from non-small-cell lung cancer A phase II study. Cancer Investig 20, 293-302. 48. Robinet, G., Thomas, P., Breton, J. L. et a . (2001). Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of...

Glossary And Abbreviations

Alkaloid - Naturally occurring cyclic organic compound containing nitrogen in a negative oxidation state, which has limited distribution in living organisms. Based on their structures, alkaloids are divided into several subgroups 11011-heterocyclic alkaloids and heterocyclic alkaloids, which are again divided into 12 major groups according to their basic ring structure. They tend to have marked physiological effects in vivo (e.g. morphine, codeine, nicotine). Allostatic responses - Changes that occur in the body in order to adapt and respond to physical or psychological change (e.g. standing, sitting, stress). They are critical to suivival, have broad boundaries and involve the sympathetic nervous system and the HPA axis. ALT - alanine aminotransferase Amino acid - Organic compound composed of one or more basic amino groups and one or more acidic carboxyl groups form the basic structural units of Prospective study - Study designed to determine the relationship between a condition and...

The Smoker's Sanctuary

The Smoker's Sanctuary

Save Your Lungs And Never Have To Spend A Single Cent Of Ciggies Ever Again. According to a recent report from the U.S. government. Centers for Disease Control and Prevention, more than twenty percent of male and female adults in the U.S. smoke cigarettes, while more than eighty percent of them light up a cigarette daily.

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