The Painless Stop Smoking Cure

Quit Smoking Magic

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Quit Smoking Magic Overview


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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...

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

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...

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...

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...

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...

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).

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.

International Variation In Rates

The remarkable international variation in cancer rates, for many of the common cancers, such as breast and prostate, seemed to many to support the traditional view that endogenous hormones could not be the sole or primary cause. The low rates of breast, prostate, and several other cancers in Asian populations and their increase toward Western rates upon migration to the United States or Europe suggested that chemical factors or other environmental agents were the major causes of these cancers. While cigarette smoking was one such obvious chemical carcinogen, which would help to explain the international variation in lung and other smoking-related cancer sites, the most obvious cause of the other cancers seemed to be diet, other lifestyle factors, or unidentified environmental agents. In 1964, an expert committee of the World Health Organization stated that the categories of cancer that are thus influenced, directly or indirectly, by extrinsic factors . . . collectively account for...

Epidemiology Of Sexual Dysfunction

Numerous population surveys in this and other countries indicate a high prevalence of sexual problems in the general population. These surveys indicate that 40 of women have evidence of psychosexual dysfunction. The corresponding number for men is 30 (25). We have more evidence concerning the prevalence of sexual problems in men than women although the data base in both groups is rapidly growing. Correlates of erectile dysfunction in men include diabetes, vascular disease, age, and cigarette smoking. Serum dehydroepiandro-sterone and high-density lipoprotein cholesterol were found to be negatively correlated with erectile problems (26). Depression was correlated with erectile function in cross sectional studies, whereas passive personality traits tended to predict who would develop impotence in a prospective study (27). Studies in other countries have, in general, found somewhat similar rates of erectile dysfunction in the same age population and also that erectile dysfunction tends...

Nutrition And Esophageal Adenocarcinoma

A further study found a statistically significant increased risk of esophageal adenocarci-noma in smokers and a strong association of alcohol with squamous-cell carcinoma of the esophagus (83). However, neither beer nor liquor drinking was shown to be significantly associated with adenocarcinoma of the esophagus, and wine drinking was associated with a significant decrease in risk.

Neoplastic Conditions

Squamous cell carcinoma forms 30-40 of oesophageal cancers and is typically seen in the mid-oesophagus of elderly patients. It is usually moderately differentiated and keratinising, ulcerates or strictures with rolled, irregular margins, involves a long segment of oesophagus and has spread through the full thickness of the wall at presentation. Palliation can be achieved by radiotherapy, ablative laser therapy or the insertion of an expanding metal stent or tube to relieve obstruction. Primary surgical resection is the treatment of choice in a medically fit patient with a locally confined lesion < 5 cm in length. If more extensive than this, resection can be facilitated by preoperative radio- chemotherapy which produces signs of tumour regression (degeneration, necrosis, fibrosis, keratin granulomas) in some 50-60 of cases, but often makes identification of tumour on gross inspection of the specimen difficult. Perforation with potentially fatal medi-astinitis is a possible...

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...

Oral contraceptives

Estrogens can cause nausea, breast tenderness and breast enlargement. Progestins can cause unfavorable changes in LDL and HDL cholesterol. Other adverse effects associated with oral contraceptives, such as weight gain or depression, are more difficult to attribute to one component or the other. Women smokers more than 35 years old who use combination oral contraceptives have an increased risk of cardiovascular disease.

Minority Groups Urban Life And Health

The overall benefit of community resources to all their residents is what Rose (1985) has called a preventive paradox, that is everybody benefits by being exposed to multiple sources of information and services (Rose, 1985). A good example of this paradox is the case of health promotion leading to positive health behaviors, such as physical activity, anti-smoking campaigns, and sexual education among adolescents. People living in urban areas are more likely to be active than those living in rural settings, regardless of their race ethnicity, and as a result less likely to be overweight (Eberhardt, et al., 2001). Cigarette smoking and birth rates among adolescents are lower in urban setting than in rural areas (Eberhardt, et al., 2001). In fact, there is evidence that black adolescents in urban cities have lower rates of smoking than whites and are more likely to initiate later in life (Bachman, et al., 1991 Mcintosh, 1995 Nelson, et al., 1995 Siegfried, 1991). However, not all...

Conclusion and Outlook

In the last 50 years, epidemiologic research has identified a large number of risk factors and preventive factors of multiple chronic diseases, yet the transfer of these findings into applied disease prevention has often remained unsatisfactory. For example, half a century after the deleterious health effects of smoking have been disclosed by carefully conducted epidemiologic studies, the global number of smokers and prevalence of smoking keep rising. A similar development appears to be seen for physical inactivity, which is likewise related to a large number of severe chronic diseases. Therefore, further development of epidemiology in aging research has to go along with research on how to more effectively translate epidemiologic study results into the practice of prevention. Preventive efforts again have to keep the entire life span in mind.

Statistical Prediction

Given the shortcomings of clinical judgment for describing functional relationships, it is important to note that sequential and conditional probability analyses have been used to analyze self-monitoring data. These statistical analyses have been used to clarify the functional relationships involved in a variety of problems including smoking addiction, bulimia, hypertension, and obesity (e.g., Schlundt & Bell, 1987 Shiffman, 1993).

Potential Strategies For Improving The Health Of Sexual Minorities Groups In The City

Other public health campaigns (e.g., to encourage smoking cessation, increase exercise, decrease excess weight, avoid driving while intoxicated, use seat belts and bike helmets) should include images and messages targeting LGBT people just as they do members of other minority groups. In addition, research into appropriate structural interventions to reduce smoking and other substance abuse for segments of the LGBT community are needed. Lastly, causes of poor health in the LGBT community that are related directly and indirectly to homophobia and its consequent stress (e.g., depression, substance abuse, violence) can most effectively be prevented by continued efforts to improve the social conditions, antidiscrimination protections, and acceptance of LGBT people.

Cultural Determinants Of Obesity

There is a general concern within the field of behavior change that the available methods are not sufficient to produce long-term improvements in lifestyle risk factors related to diet and physical activity, including obesity, as well as cigarette smoking (15). The need for effective long-term weight control strategies has become especially urgent in light of recent increases in obesity

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,...

Placental Alkaline Phosphatase

Placental alkaline phosphatase (PLAP) is the fetal isoenzyme of the ubiquitous adult alkaline phosphatase. It is normally expressed in utero and in children less than 1 year of age and functions as a protein phosphotyrosine phosphatase, catalyzing the abstraction of inorganic phosphate from phosphate esters. Although widely accepted as a reliable histo-logic marker for seminoma, its merit as a serum tumor marker is uncertain (Figure 7-5). In seminoma, serum PLAP levels are elevated in 50 to 72 of patients, with higher stages more frequently presenting with elevated levels.20-22 In one multicenter prospective trial, the incidence of elevated PLAP in seminoma was greater than that of hCG or LDH (56 vs 35 and 34 , respectively). In addition, PLAP was found to have the highest sensitivity for detecting metastasis.23 Specificity, however, is poor. Elevated levels can be seen in smokers and in persons with other malignancies, including, lung, ovary, breast, and gastrointestinal...

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...

Biological And Molecular Actions

Figure 4-13 shows an overview of some of the main features of water balance (additional discussion is presented in Chapter 15). The hypothalamic osmoreceptor detects elevations in serum tonicity. The mechanism is thought to involve the shrinking of the osmoreceptor neuron to the point where a signal (chemical or electrical) is generated and transmits this signal down its axon to its nerve ending. Alternatively, the changed ionic environment produces a conformational alteration in the osmoreceptor, which generates the signal. The signal is then received by the cell body of the vasopressinergic neuron and transmitted to its own nerve ending for the release of VP-NP. Signals to baroreceptors that control the release of AVP-NP are exemplified by emotional states that inhibit the release of AVP-NP and lead to transitory frequency of urination. Nicotine intake and pain may also operate through baroreceptors of the CNS repressive center, which may stimulate AVP-NP release through adrenergic...

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.

Causes and symptoms

How nicotine works Nicotine is the main addictive drug among the 4,000 compounds found in tobacco smoke. Such other substances in smoke as tar and carbon monoxide present documented health hazards, but they are not addictive and do not cause cravings or withdrawal symptoms to the extent that nicotine does. Nicotine is both a stimulant and a sedative. It is a psychoactive drug, meaning that it works in the brain, alters brain chemistry, and changes mood. Once tobacco smoke is inhaled, nicotine passes rapidly through the linings of the lungs and into the blood. It quickly circulates to the brain where it indirectly increases the supply of dopamine, a chemical in the brain that affects mood. Dopamine is normally released in response to pleasurable sensations. Nicotine, like cocaine or heroin, artificially stimulates the release of dopamine. This release accounts for the pleasurable sensation that most smokers feel almost as soon as they light up a cigarette. Nicotine also decreases anger...

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...

Drug Dependency Assessment

Similar withdrawal symptoms can also occur with sedatives, anticonvulsants such as clonazepam and carbamazepine, and muscle relaxants such as carisoprodol (11-13,127). Frequent nicotine and caffeine use is also an important consideration in pain management. Nicotine abstinence symptoms can cause restlessness, palpitation, and irritability, and caffeine abstinence can precipitate headaches.

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).

Joel N Hirschhorn Celeste Leigh Pearce David Altshuler

Some circumstances, such as the role of smoking in lung cancer,4 a single environmental exposure can make a major contribution to disease risk. In other cases, such as early-onset breast cancer, exposure to a mutation in a single gene can be both necessary and sufficient to cause dis-ease.5,6 In the population, however, most cancers are attributable neither to a single identifiable environmental factor nor to mutation of a single gene. Rather, cancer typically results from a combination of factors inborn and somatically acquired mutations in gene sequence, one or more environmental factors, and certainly an element of bad luck. Such disorders are referred to as complex traits. This complexity has thus far befuddled researchers where the web of causality is broad, any single strand plays only a minor role and eludes most efforts at discovery.

Specific interventions

Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina, coronary artery procedures, or evidence of clinically significant myocardial ischemia. CHD risk equivalents include clinical manifestations of non-coronary forms of atherosclerotic disease, diabetes, and > 2 risk factors with 10-year risk for hard CHD > 20 . Risk factors (RF) include age (male > 45 years, female > 55 years or premature menopause without hormone replacement), positive family history for premature CHD (in first-degree relatives < 55 years and first-degree female relatives < 65 years), cigarette smoking, hypertension (blood pressure > 140 90 mmHg or taking antihypertension drugs), HDL < 40 mg dl (1.0 mmol l). If HDL cholesterol is over > 60 mg dl (1.6 mmol l), subtract one risk factor from the total (adapted from Dub 2000 and Schambelan 2002). Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina,...

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)....

Spices as Antioxidants

Spices can be used in foods to help fight the toxins created by our modern world. Heat, radiation, UV light, tobacco smoke, and alcohol initiate the formation and growth of the free radicals in the human body. Free radicals damage the human cells and limit their ability to fight off cancer, aging, and memory loss. Many spices have components that act as antioxidants and that protect cells from free radicals (Table 9).

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.

CoExistence of HS and CD

A clinical association between HS and CD has been described in some cases reports 31-33 and in one case series 34 . Gower-Rousseau et al. reported the occurrence of HS in two first-degree relatives of patients with CD 35 . This finding suggests a common genetic susceptibility for the two diseases. In the study by Church et al. 34 , CD lesions were found in 24 out of 61 patients with HS. In our series of 2926 patients with CD, 18 (0.6 ) have such an association. This figure should be considered as minimal, as a systematic search for HS was not made. Of note, the proportion of active smokers was 78 in our patients with both diseases. Clinical characteristics of patients with HS and CD in the two latter studies are given in Table 7.1. CD patients with HS differ from other CD patients by a higher frequency of colonic and perianal involvement, an increased need for immuno-suppressants, and, more importantly, a very unusual need for proctectomy and definitive ileos-tomy. Finally, the...

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...

Cities Are Different from One Another and May Change Over Time

Epidemiologic inquiry in health presupposes that there are identifiable (and modifiable) factors that influence health. Typically, public health studies imply, for example, that we can generalize about how different foods will affect health across individuals, at least within the confines of effect modification across groups (e.g., age groups) ) or under different circumstances (e.g., at different levels of caloric intake). However, cities are characterized by multiple factors (e.g., size, population density, heterogeneity etc.) that in many ways make each city unique. The complexity of cities and of city living may mean that urban characteristics that are important in one city may not be important in others, limiting the generalizations that can be drawn about how urban living influences health. Further complicating this task is the fact that cities change over time with implications for the relative contribution of different factors in determining health in cities. For example,...

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,

Types Of Group Level Studies Used In Urban Health

In general, the outcome Y could be either continuous (number of cigarettes per day smoked), binary (smoking cigarettes yes no), or censored binary (time to cessation of smoking). The exposure X could be either continuous and or binary. Furthermore, X could measure an existing condition (such as gender, race, weight) or a new intervention (such as a new treatment Vs placebo) or even be a vector of multiple exposures. A given number (say N) of subjects are measured for Xand Y, and statistically compared to determine if Xis related to Y. Either a hypothesis testing or inferential statistical estimation approach may be used.

Group Mediated Effects Are of Interest

Several settings occur where the effect being studied is mediated through a neighborhood or group and there are a limited number of these groups neighborhoods to study. For example, smoking cessation classes are often taught to classes (i.e. groups) of 15 students and it may be of interest to know if positive and or negative synergies form from interactions among the students in the same class. Or a city may have k (e.g., k 59) distinct neighborhoods. It may be of interest to know whether the neighborhood a person lives in (or characteristics of that neighborhood) is related to his or her level of depression.

Antioxidants And Aging

Researchers at the National Cancer Inst itute (NCI) did a classic prospective study of the health effects of smoking in the 1960s (Giere 1997), which provides a model for other researchers, such as the Sw iss group that st udied antioxidant s and memory. From more than 400,000 men who volunteered for the smoking study, the researchers selected about 37,000 smokers and an equivalent number of nonsmokers for comparison. The key strength of this large-scale st udy was that each smoker was paired with a nonsmoker, and members of these pairs were similar in obvious characteristics such as age and ethnic group, as well as a host of other characteristics that might influence health, ranging from religion to the average amount of sleep per night. Not surprisingly, the death rate of smokers after only 3 years was t wice that of nonsmokers. There are several pitfalls of prospective studies compared to the kinds of randomized experiments that have been used to study the effects of vitamin C on...

Overexpression of Tumor Suppressor Genes and Apoptosis Inducing Genes

The fact that overexpression of tumor suppressor genes and apoptosis-inducing genes can induce cell-cycle arrest or apoptosis has led to numerous experimental and clinical investigations into their use as anticancer therapeutics (37,40). Transfer of various tumor suppressor genes directly into cancer cells has been demonstrated to suppress tumor growth by inducing apoptosis and cell-cycle arrest while also exerting lethal bystander effects. Adenovirus-mediated p53 gene therapy has produced promising results in lung cancer and head and neck cancer, among cancers. Combination of tumor suppressor gene therapy with conventional anticancer therapy has been shown to yield synergistic therapeutic benefits. In clinical trials, tumor suppressor genes, especially the p53 gene, have been well tolerated and produced favorable clinical responses, including pathologically complete responses, in subsets of patients with advanced disease or cancers resistant to conventional therapy (37).

Candidate Mechanisms For Stable Druginduced Changes In The Brain

One such mechanism is a change in the shape or the number of excitatory synapses. This mechanism contributes to long-lasting changes in synaptic strength as a result of LTP and other forms of learning (37). Recently, changes in dendritic spines have been found after chronic drug administration. Repeated treatment with either amphetamine or cocaine increased dendritic branching, spine density, and the number of branched spines in Golgi-stained medium spiny neurons in the NAc and pyramidal neurons in the prefrontal cortex, effects which persisted at least 1 mo (38,39). Very similar alterations were observed in rats allowed to self-administer cocaine for 1 mo (40). Interestingly, nicotine produced effects similar to those found with cocaine and amphetamine perhaps more robust (41) , whereas chronic morphine produced effects opposite to those observed after cocaine or amphetamine, i.e., decreases in spine density and dendritic branching (42). The most important point is that these changes...

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.

Adverse Reactions

Traditionally, ginseng is not recommended with other stimulants such as caffeine and nicotine and a case report exists of a 39-year-old female experiencing menometrorrhagia, arrhythmia and tachycardia after using oral and topical ginseng along with coffee and cigarettes (Kabalak et al 2004).

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.

Recognition And Treatment Of Pseudohit

HIT is a relatively common complication of heparin therapy. It may be even more common in patients who have baseline platelet activation and PF4 release, as occurs in adenocarcinoma-associated DIC or DKA. Therefore, a patient with early thrombocytopenia attributable to a pseudo-HIT disorder may subsequently develop clinically significant HIT antibodies (Greinacher, 1995) (Fig. 5). Another example is that of a patient with lung cancer and DVT who developed a platelet count rise during intravenous heparin therapy, followed by recurrent thrombocytopenia and, ultimately, venous limb gangrene during anticoagulation with warfarin and ancrod (Fig. 7). In this situation, one might have expected platelet count recovery during a second course of heparin. However, an intravenous heparin challenge resulted in worsening of thrombocytopenia, and the patient had a strong positive assay for HIT antibodies, indicating the concurrence of cancer-associated DIC and HIT.

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...

Other Methodological Issues

Failure to take these insights into account leads to a ''low birth weight paradox,'' viz., puzzlement over the finding that ''LBW babies in high-risk populations usually have lower mortality than LBW babies in better-off populations'' (Wilcox 2001a 1234). A prime example occurs in what at first glance seems to be an enigmatic effect of smoking. While it early became clear that both low birth weight and infant mortality are more likely among babies of mothers who smoke, it was also discovered that ''LBW babies born to mothers who smoked had lower infant mortality than the LBW babies of mothers who did not smoke'' (Wilcox 2001a 1234 emphasis in the original). The puzzle is solved when infant mortality is plotted by relative birth weight (adjusted to z-scores), in which case '' m ortality with mother's smoking is higher across the whole range of weights'' (Wilcox 2001a 1237).

Antimicrobial Activity

In vitro and animal studies show that the organosulfur components of garlic suppress tumor incidence in breast, blood, bladder, colon, skin, uterine, esophagus, and lung cancers. Potential mechanisms include decreasing nitrosamine formation, decreased bioactivation of carcinogens, improved DNA In summary, although the data is encouraging, more studies are needed before definitive conclusions can be made about the effect of garlic on the prevention or the cause (in the case of lung cancer) of cancer, especially with garlic supplements.

Gene Replacement Therapy

The p53 gene (also known as TP53) encodes a 593-amino acid phosphoprotein that plays critical roles in several cell processes including cell-cycle regulation and control of apoptosis (16-18). p53 gene mutations are frequent in tumor cells and have been associated with cancer progression and the development of resistance to both chemotherapy and radiation therapy (19-21). The development of gene transfer techniques has facilitated transduction of tumor cells with wild-type p53 (wt-p53). Preclinical studies both in vitro and in vivo have shown that restoration of wt-p53 function can induce apoptosis in cancer cells. Intratumoral injection in animal models of retroviral or adenoviral wt-p53 constructs results in tumor regression for a variety of different tumor histologies, including non-small-cell lung cancer (NSCLC), leukemia, glioblastoma, and breast, liver, ovarian, colon, and kidney cancers (22-28). Several preclinical studies have indicated that gene therapy with Ad-p53 has useful...

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,...

Influence of Drugs Alcohol and Tobacco on Metal Metabolism and Toxicity

Smoking may affect the uptake and effects of metals in several ways. A discussion in relation to carcinogen-esis of arsenic compounds is given in Section 3. The content of carbon monoxide, various organic compounds, and a number of toxic metals (e.g., cadmium, nickel, mercury, and lead) are probably of importance in explaining the increased carcinogenicity of combined exposures to carcinogenic metals metalloids and smoking, compared with single exposures, as show in several studies performed in the working environment (e.g., Lundstrom et al., 2006).

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.

No Is Required For The Induction And Expression Of Behavioral Sensitization To Psychostimulants

NO IS INVOLVED IN THE REWARDING EFFECTS OF COCAINE, ALCOHOL, AND NICOTINE, BUT NOT IN THE AVERSIVE EFFECT OF LiCl Repeated administration of a drug with rewarding properties in a specific environment (e.g., black or white compartment of a cage) causes conditioned place preference (CPP). A drug with aversive properties such as LiCl elicits conditioned place aversion (CPA) animals spend less time in the drug-paired compartment compared to the time they spent in the same compartment before drug administration. The rewarding effect of cocaine, alcohol, and nicotine was investigated in the CPP paradigm (25-27). In the first experiment, Swiss Webster mice were treated with cocaine (20 mg kg) in one compartment of the cage and with saline in the other compartment. Drug and saline injections were given in alternate days for a total of 8 d there were four drug sessions and four saline sessions. On d 9, animals received a saline injection and had the choice of moving freely between the two...

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...

Specific Multicultural Issues

In general, among many Hispanics, spirits, a divine providence, or supernatural events govern the world and the individual cannot control or prevent adversity resulting from these events. This belief may result in a sense of vulnerability and lack of control in the presence of adverse events, which may compete with the goals of therapy. For example, if a Hispanic with HIV (not AIDS) believes that no protections exist against problems with a root in fatalismo, a treatment plan with the goal to create a sense of hope by emphasizing positive events in the future would fail. In many instances, AIDS is developed 10 to 15 years after the individual has been infected with HIV and a significant percentage of persons with HIV have died because of other problems including drug abuse, injuries, suicide, homicide, and lung cancer (see Hoffman, 1996, p. 19). A sense of fatalismo would prevent Hispanic clients with HIV infection to see that despite the progressive course, absence of curative...

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.

Basic Fibroblast Growth Factor

Basic fibroblast growth factor (bFGF) was one of the first angiogenic factors to be characterized and since then has been studied extensively. It induces tube formation in collagen gels, modulates integrin expression and gap junction intercellular communication, and it upregulates VEGF, VEGFR2, and uPAR in vitro (44). bFGF stimulates both lymphangiogenesis and angiogenesis in a mouse corneal lymphangiogenesis model and up-regulats VEGF-C expression in vascular endothelial and perivascular cells (45). It is one of the most potent angiogenic factors and high serum levels upon diagnosis are associated with poor outcomes for cases of lung cancer (46).

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).

Case Studies 41 Airborne Particles and Morbidity and Mortality

Because of the sweeping consequences of the new standard and the potential costs of its implementation, the certainty of the underlying scientific evidence was questioned and a substantial national research agenda was initiated with guidance from a committee of the National Research Council (National Research Council (NRC) and Committee on Research Priorities for Airborne Particulate Matter, 1998). Because diverse microenvironments contribute to exposure to airborne particles, the contribution of outdoor sources to total personal exposure to particles was addressed in a number of locations. In these studies, participants wore particle monitors and noted their time-activity, and particle measurements were made in a number of key microenvironments. Some of the studies targeted those groups considered to be at increased risk from particle exposure. Overall, the studies showed that outdoor air pollution is a significant determinant of particle exposures, particularly for persons who do...

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)

Availability Of Overthecounter Sales Data

Bought cough syrup and tissues is more likely to have an acute respiratory illness (or an acquaintance or child with respiratory illness) than someone who purchased cough syrup and a pack of cigarettes. The major barrier to obtaining these additional data is the reluctance of retailers to provide the data due to concerns about the volume of data they would have to process on behalf of a biosurveillance organization, proprietary business concerns, and that participation in loyalty card programs may be adversely affected.

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...

Serthr Kinase Inhibitors

Inhibitors of the Ras-Raf-Mek-Erk pathway have great therapeutic potential, as mutated Ras is the hallmark of many cancers. Mutated Ras occurs in 30 of all human tumors, in 80 of pancreatic cancers, in 50 of colorectal cancers, in 40 of lung cancer, and in 20 of hematopoietic malignancies. So far, no real success has been achieved in developing Ras inhibitors, but promising developments are reported in the development of Raf and Mek inhibitors. A recent study 73 shows that mutations that activate the kinase activity in B-Raf occur in 66 of human melanomas, suggesting that Raf kinase inhibitors (such as the recently reported Onyx Bayer compound BAY 43-9006 74 ) (Fig. 9) may be utilized to treat metastatic melanoma. Mek inhibitors such as PD 184352 75 are also very promising. PD 184352 (Fig. 9) is a highly potent and selective inhibitor of Mek that is orally active. Tumor growth has been inhibited as much as 80 in mice with colon carcinomas of both mouse and human origin after treatment...

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...

Products Available

Two commercial forms of the herb are available. White ginseng consists of the dried root and red ginseng is prepared by steaming the fresh, unpeeled root before drying (9). Many different formulations of the herb are available including capsules, gelcaps, powders, tinctures, teas, slices to eat in salads, and whole root to chew. There are also a wide variety of products that claim to contain ginseng such as ginseng cigarettes, toothpaste, cosmetics, soaps, beverages (including beer), candy, baby food, gum, candy bars, and coffee. Prices vary widely based on the quantity and quality of the ginseng root used (10). Tinctures are more expensive but last for years. Powder capsules are cheaper but have a shelf-life of only 1 year (11).

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