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Quit Smoking Magic Summary

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Highly Recommended

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Initial Laboratory Investigations other than Radiodiagnosis and Histo Cytological Analysis to Assure Diagnosis and

Besides biopsy and cytopathological investigations there are some clinical and serological (paraneo-plastic) signs that can point us in the right direction in the search for lung cancer. In addition to the question of operability and sentinel node detection, these findings can also be helpful in the differential diagnosis between small-cell cancer, which is mostly not operable, and non-small-cell cancer, which can be more closely evaluated from the aspect of operability.

Primary Multicentricity of Lung Cancer Compatibility with the SLN Concept

In lung cancer treatment, in the clinical and radio-diagnostic investigations synchronous multicentricity and back-metastasis to the lungs must be distinguished. It is essential that this is done before mediastinoscopy and or SLN labeling is started. In this context it must also be emphasized that primary multicentricity does not contraindi- With regard to this point, it must be emphasized that, at least in cases with ipsilateral multi-centricity, the surgical treatment is basically not different from lobectomy or pneumectomy procedures in cases with unifocal lung cancers. In cases with bilateral cancer foci, in addition to lobectomy or pneumectomy on the side with more intensive cancer involvement, laser and irradiation therapy of smaller foci on the contralateral side are considered and performed, as well as lymphadenectomy. Because some of these multifocal cancer types have low degrees of malignancy, the 78.3 5-year survival rate published by Kawashima (2002) is not too astonishing.

Significance of PET in Staging Lung Cancer Introductory Remarks

There is as yet no uniform system for detecting tumor-free or tumor-infiltrated SLNs in lung cancer with high levels of sensitivity and specificity. It will be easily understood that the development of a plausible and rational basic concept for this tumor type is extremely difficult. Fig. 4. Lung cancer with hilar and mediastinal lymph node metastases. The coronal PET image shows an area of focally increased metabolic activity in the upper lobe of the right lung (P). In addition, there are positive lymph nodes in the right hilar region and in the mediastinum (LN)

Demonstration of Lung Cancer Diagnosis in Scarce Tissue by FNAC

Figures 8-10 show a series of cytology smears demonstrating the different diagnoses. The next series (Figs. 11-14) shows cytopathological pictures of FNAC smears of small-cell lung cancer (Giemsa and immunohistochemical staining for cytokeratins 8, 18, 19). This nonaggressive (nonin-vasive) method in connection with other clinical results (imaging investigations) helps to define whether the search for SLNs is indicated and whether the cancer is operable.

Exclusion of Primary Mediastinal Neoplastic Lesions in Differential Diagnosis Against Mediastinal Metastases of Primary

Primary lung cancers can be very small and are primarily not detected by the diagnostic methods described. Fig. 7. Combined histo- and cytopatho-logical techniques applied to ensure lung cancer diagnosis. a Endoscopic biopsy techniques plus exfoliative cytology. b Transthoracic aspiration cytology (FNAC). c Transcarinal puncture of bifurcation lymph node(s) in advanced cases. Diagnoses made by investigations including typing by histopathology only in biopsies were secure in 84 of cases, whereas when all histo- and cytopatho-logical techniques are used the diagnoses are secure in 96 Fig. 7. Combined histo- and cytopatho-logical techniques applied to ensure lung cancer diagnosis. a Endoscopic biopsy techniques plus exfoliative cytology. b Transthoracic aspiration cytology (FNAC). c Transcarinal puncture of bifurcation lymph node(s) in advanced cases. Diagnoses made by investigations including typing by histopathology only in biopsies were secure in 84 of cases, whereas when all histo-...

Put Out the Cigarettes

Studies show that smokers don't remember as well as nonsmokers. That's no surprise when you consider that smoking is a risk factor for cardiovascular disease and other illnesses that contribute both directly and indirectly to memory loss. Smoking also damages the lungs and constricts blood vessels to the brain, depriving it of oxygen and possibly harming neurons. British public health researchers have been following more than five thousand people born in 1946, surveying their smoking behavior at various times over the years. In 1999, when the subjects were fifty-three years old, the researchers explored the relationship between smoking status and performance on cognitive tests. Even when the data were controlled for sex, childhood cognitive ability (measured at age fifteen), educational achievement, and occupational class, the researchers found that smoking correlated with steeper declines on measures of verbal memory and visual processing speed. Importantly, they also found better...

Chemotherapy Regimens for Non SmallCell Lung Cancer

Surgery and radiotherapy remain the best treatment options for resectable non-small-cell lung cancer (NSCLC). The role of adjuvant chemotherapy in successfully resected NSCLC is still highly controversial. Whereas the largest trial (IALT, International Adjuvant Lung Cancer Trial) (see Tona-to 2002) showed a small but significant survival benefit for patients treated with cisplatin-based chemotherapy, the Italian trial (ALPI) (see Alexa-nian and Torri 2000) and the UK trial (Big Lung Trial) (see Evans 2004) did not show any significant differences.

Pattern of Distant Hematogenous Metastases from Lung Cancer

The pattern summarized for distant metastasis is highly characteristic for lung cancer, and especially for the small-cell (anaplastic, oat-cell) type but high-grade adenocarcinomas and anaplastic squamous cell cancers also develop metastases in the organs listed (see Fig. 5). After confirmation of the diagnosis of lung cancer by biopsy or cytology and before local SLN labeling, N-staging, and surgical treatment (lobectomy, pneumectomy) the organs listed and the skeleton must be carefully checked by radio-diagnostic imaging to exclude the presence at least of any currently detectable distant metastasis.

Nicotine from bad habit to chemical dependency

Most smokers do not continue to smoke out of choice, but because they are addicted to nicotine. This statement in the latest edition of the report by the Royal College of Physicians that launched the public campaign against smoking in the early 1960s reflects a significant shift in the war against tobacco and a confirmation of the current status of the concept of addiction. Whereas earlier editions had characterised smoking as a bad habit, the February 2000 version, bluntly titled Nicotine Addiction in Britain, claims that smokers are in the grip of a chemical dependency. According to the RCP report, its recognition of the addictive character of nicotine was a result of new researches in psychopharmacology, involving biochemical and behavioural studies in animals in humans. It seems probable that a greater influence was the growing popularity of notions of addiction in society generally. The RCP report conducted a detailed comparison of nicotine with heroin, cocaine, alcohol,...

Nicotine Addiction

Cigarette smoking is the leading cause of preventable morbidity and mortality in the United States among all ethnic groups. National and regional surveys have found that on average Latinos smoke at lower rates than do whites and that among current smokers, Latinos smoke fewer cigarettes per day than do these other groups. Data from the 1997 National Health Interview Survey (NHIS) showed that the overall prevalence of current cigarette smoking was lower for Latinos (20.4 ) than for whites (25.3 ), although rates vary substantially by sex (Centers for Disease Control and Prevention 1999). For Latino men, the rates are approaching those of white men (26.2 vs. 27.4 ), whereas for Latina women, the rates are low relative to white women (14.3 vs. 23.3 ) (Centers for Disease Control and Prevention 1999). In the United States, from 1988 to 1995, the number of Latinos who reported being current smokers increased from 2.8 to 3.2 million. Concurrently, the number of Latinos who reported quitting...

Lung Cancer

Routine and specialized radiological examinations (including CT and MRT) of the thoracic situs and mediastinoscopy, with histopathological investigations of excised lymph node or soft tissue specimens, are the most important preoperative methods of staging for lung cancer and are helpful in further decision-making however, there is no practicable and clinically proven strategy for pre-operative determination of the exact pattern of local lymphogenic tumor spread in the sense of the SLN concept and detection of early metastases in the N2 and N3 stages. In Fig. 9 the possibility of peritumoral 99mTc-nanocolloid injection is documented (Fig. 9 a). Such strategies can be discussed at least in the early stages of non-small-cell lung cancers. Fig. 9. Lung cancer. Locoregional spread detected by local submucous injection of tracer around the tumor (a). Systemic administration, e.g. of ultrasmall paramagnetic particles of iron oxide (US-PIO), can help in finding filling defects of lymph nodes...

Smoking Cessation

Offers information and support for smokers who want to quit. Its website provides links to support groups, or you can call for infor-226, mation on a group near you. Continues to research the latest developments in lung care and has many programs and strategies for fighting lung disease. The Quit Smoking Action Plan offers specific recommendations for selecting a personalized three-step plan (preparing to quit, using medications, and staying smoke-free) to free yourself of cigarettes and stay that way.

The Sentinel Node Concept Related to Main Tumor Types and Subtypes Applicability in Daily Routine Work

Lung 301 of Lung Cancer 301 Primary Multicentricity of Lung Cancer Compatibility with the SLN Significance of PET in Staging Lung Cancer 305 Diagnosis Against Mediastinal Metastases of Primary Lung Cancers 310 N-level-dependent Survival 317 Chemotherapy Regimens for Lung Cancer

Quantitative Measurements

Another source of inaccuracy is the distribution of FDG in different body compartments. Fat, for example, has a lower FDG uptake than other tissues. Therefore, FDG uptake in tumors will be overestimated in heavy patients. To correct for these effects the use of the lean body mass or the body surface area has been suggested (Zasadny et al. 1993 Kim et al. 1996). However, when these correction methods were applied in a study population of breast cancer patients no better results were obtained than with other SUV approaches to differentiating between benign and malignant breast tissue (Avril et al. 1997). As a result of the competition between the transport of endogenous glucose and FDG molecules into the cell, FDG uptake in tissue is sensitive to variations in blood glucose levels. In patients with lung cancer a markedly decreased FDG uptake (41.8 15 ) was found when plasma glucose levels were about double those recorded in fasting conditions (Langen et al. 1993). The lumped constant...

The Oaths Message For Today

Problem-solving by comparing cases, casuistry, is one way to try to understand the Oath's implications for the medical ethics problems of our time. Casuistry has a long history in philosophy, theology, ethics, and medicine.29 In medicine, physicians often approach a medical or ethical problem by comparing one case with another. Is this person's disease more like a classic case of pneumonia or a typical case of lung cancer How is this case of discontinuing life support similar to, or different from, that case of euthanasia The similarities and differences between cases illuminate significant facts and values and can clarify a diagnosis or help us decide whether the solution to one case applies to the other. Casuistry is a difficult art. Superficially similar cases can differ by morally significant details. For example, a person with incurable cancer may have a right to refuse life-sustaining treatments, though some believe that feeding by means of a tube into the stomach is a form of...

Diagnosis of Lymph Node Metastases

PET offers particular advantages in evaluating lymph nodes. When CT is applied the size of the lymph nodes is a determining factor, although even lymph nodes that are normal in size can be tumor involved, just as lymph nodes can be non-specifically enlarged. In detection of breast cancer and melanoma and in the mediastinal staging of lung cancer, FDG-PET is clearly superior to conventional imaging modalities. In principle, PET permits the recognition of positive lymph nodes regardless of size, but has limited sensitivity in detecting microscopically small tumors. Spatial resolution is an important factor, as existing PET scanners do not have sufficiently high resolution to enable detection of micrometastases. The further development of PET scanners and new imaging processes should, however, improve the spatial resolution in the future.

Health As A Social And Political Undertaking

Constitutional or statutory obligation to promote health, yet the private sector is affected by governmental actions. Government regulates private and nonprofit actors to ensure that they perform in ways that promote health (e.g., occupational health and safety rules, licenses, inspections, and nuisance abatements). Government provides economic incentives for engaging in health-promoting behavior (e.g., tax inducements to employers who provide health care benefits) and disincentives for engaging in risk behavior (e.g., taxes on cigarettes). Furthermore, the interest in and civic role for private- and nonprofit sector participation in health activities has been growing. For example, employers have recognized the benefits of making health and safety high priorities (WBGH, 2000). When businesses and voluntary organizations support the creation and maintenance of environments that are healthy and safe, they reap additional benefits from having healthy employees and satisfied consumers or...

Microsatellite instability in cancer progression

Microsatellite instability has been encountered in several forms of human cancer, e.g. in colonic (Aaltonen et al., 1993 Ionov et al, 1993 Thibodeau et al., 1993 Patel et al., 1994), endometrial (Risinger etal, 1993 Burks etal., 1994), gastric (Han etal, 1993 Peltomaki etal., 1993 Seruca et al., 1995 Dossantos et al., 1996), pancreatic (Han et al., 1993), and oesophageal cancers (Meltzer et al., 1994). This abnormality was not found in cancers of the breast, lung or testis (Peltomaki et al, 1993), but recent reports do cite microsatellite instability in these tumours. MI may occur infrequently in sporadic and in familial breast cancer (Jonsson et al., 1995) and at a high frequency in invasive lobular breast carcinoma (Aldaz et al., 1995). Merlo et al. (1994) has stated that it occurs frequently in small cell lung carcinoma. Adachi et al. (1995) found no MI in small cell lung carcinoma, but did find MI in about one-third of non-small cell lung cancers. Instability of microsatellite...

Healthrelated roles of Pcarotene

The strongest epidemiological evidence suggesting high intake of fruits and vegetables might give protection against lung cancer came from prospective studies in which low plasma p-carotene was associated with a higher incidence of lung cancer. Carotenoid intake was associated with reduced cancer risk in 8 prospective studies and 18 out of 20 retrospective studies (Zeigler et al, 1996). Based on the results of these studies, three major intervention studies investigated the protective effect of p-carotene in the prevention of lung cancer (a) The alpha-tocopherol, beta-carotene (ATBC) Cancer Prevention study, was a randomised-controlled trial that tested the effects of daily doses of 50mg (50 IU) vitamin E (all-racemic a-tocopherol acetate), 20 mg of p-carotene, both or placebo in a population of more than 29 000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases...

Eliseo J Prez Stable MD Anna M Npoles Springer PhD

Only in the past two decades, and underestimation of population denominators also may distort reported rates. In this chapter, we present an overview of available national data on indicators of mortality and morbidity, with an emphasis on conditions that disproportionately affect Latinos. We then discuss awareness of prevention issues and risk behaviors, with a special emphasis on nicotine addiction, attitudes toward physicians and medical care, seeking help for medical care, and barriers to medical care.

Other roles of vitamin E

Despite the use of high doses of vitamin E, large changes in the vitamin content of blood and liver and extended periods of study in animals and humans (smokers and non-smokers), vitamin E does not appear to have affected repair products of oxidative DNA damage, sister-chromatid exchanges in peripheral lymphocytes or DNA adducts in lymphocytes (Morrissey and Sheehy, 1999).

The Physical Environment As A Determinant Of Health

The importance of place to health status became increasingly clear in the last decades of the twentieth century. The places in which people work and live have an enormous impact on their health. The characteristics of place include the social and economic environments, as well as the natural environment (e.g., air, water) and the built environment, which may include transportation, buildings, green spaces, roads, and other infrastructure (IOM, 2001b). Environmental hazards in workplaces and communities may range from tobacco smoke to pesticides to toxic housing. Rural areas may present increased health risks from pesticides and other environmental exposures, whereas some environmental threats to health can occur because of urban living conditions.

Absorption and deficiency

When the body pool falls below 300 mg vitamin C there is evidence of impaired function (Hodges et al, 1969). Plasma vitamin C levels are sensitive to recent dietary intake with values < 11 mmol L indicating biochemical depletion (Sauberlich, 1975). The early symptoms of vitamin C deficiency are fatigue, lassitude, loss of appetite, drowsiness, insomnia, feeling run-down, low resistance to infection and petechiae (minor capillary bleeding). Those most at risk of vitamin C deficiency are cigarette smokers, alcohol users, institutionalised elderly and people on certain drugs. Deprivation of vitamin C for long periods leads to scurvy, characterised by weakening of collagenous structures, resulting in widespread bleeding. Scurvy in infants results in bone malformations. The earliest clinical signs of deficiency are bleeding gums and loosening of teeth. Today, scurvy is relatively rare. An LNRI of 10mg d for adults has been shown to prevent scurvy in the UK and elsewhere but this level...

The Social Determinants Of Health

Most recently, social epidemiologists and other researchers have focused on identifying the social equivalents of leaded gasoline and environmental tobacco smoke. Among the greatest advances in understanding the factors that shape population health over the last two decades, and clearly

Diseasenutrient interactions

Disease and stress lower both plasma and leukocyte ascorbate concentrations (Thurnham, 1994, 1997). It has been recognised for many years that smokers have lower plasma ascorbate concentrations than non-smokers, even when dietary intake is taken into account. The effect is similar to that seen during surgical stress or infection but the stress of smoking is more easily studied (Thurnham, 2000). It has been argued that smokers have an increased turnover of vitamin C, so in order to maintain their body pool and circulating levels at similar levels to those of non-smokers, intake would need to be higher, 80mg d (Kallner et al, 1981 Smith and Hodges, 1987). However, an alternative explanation might be that vitamin C can act as a pro-oxidant in plasma, hence the body may be lowering concentrations to minimise the potential pro-oxidant damage caused by smoking and other stresses (Thurnham, 1994). The mechanism which reduces plasma vitamin C is also linked to the processes activated by the...

The Effects Of Poisoning By Organophosphate Insecticides

Plants were known to contain insecticidal substances, and one of the first of these to be used, in the middle of the eighteenth century, was nicotine. A solution made from soaking tobacco leaves was found to be effective. Pyrethrum, contained in the flowers of the chrysanthemum plant, is a very effective insecticide and may have been known for centuries.

Data Collection And Processing

As already indicated, much of the data in medical studies is captured on paper-based forms, although there is an increasing trend for electronic data capture. The advantage of electronic forms is that range and cross-checks (checking the consistency of the new data with itself and with that already in the database) and value checks can be instantly applied. In addition missing values can be immediately queried, and irrelevant questions, such as asking a non-smoker for details of cigarette consumption can be skipped. However, paper forms are often used for convenience.

Listening to Self Help Recordings While You Sleep Can Help You Learn

Although a multitude of tapes and CDs are available on the Internet purporting to help people improve themselves (such as learn a language, lose weight, or quit smoking) while they sleep, I've yet to see any solid research showing they're effective. What sometimes confuses this issue is that there is abundant evidence that a good night's rest can improve test performance compared to a night of sleep deprivation. Sleep does play a role in learning, but first you need to be awake while you're taking in new information.

And Infant Health Promotion

The act authorized the development of a national surveillance program designed to improve the understanding of maternal complications and mortality, authorized research into risk factors and prevention, and authorized public education campaigns to promote healthy pregnancies. Finally, it authorized funding for research initiatives and programs to prevent drug, alcohol, and tobacco use among pregnant women.

Populationlevel Preventive Interventions

Although many studies have looked at the effectiveness of preventive measures, few have studied universal, population-level strategies. In some cases, however, such as tobacco use prevention and automobile-related injury prevention population-based strategies (e.g., laws) have been used successfully, largely because of recognition of the broad determinants of health. Results of these interventions indicate that, at least in some cases, a population-level strategy or, to use Gordon's classification, a universal measure may be more optimal and cost-effective than interventions targeted further downstream (i.e., at the individual level). Acting on the most upstream level of determinants of health typically means the level of national policy. This may help shift national norms and values that lead to the passage, adoption, and ultimately, success of the respective legislation, as in the case of seat belt legislation, which has steadily and gradually normalized this behavior across...

Area vasculosa See area opaca

Arecoline An alkaloid isolated from Areca catechu (betel palm) and one of the major pharmacologically active components a muscarinic acetylcholine receptor agonist. Effects on the central nervous system are similar to those of nicotine. Has also been used medicinally as an anthelminthic.

The Regulation Of Lifestyle

While clinical trials have shown the benefits of stopping cigarette smoking, many of the changes in lifestyle that are being promoted by Western governments are based on information lacking in solid evidence. It is unpardonable to try to alter the diet of an entire population without sufficient information. The 'big four' injunctions of health promotion to stop smoking cigarettes, to eat a healthy diet, to drink alcohol in moderation, and take regular exercise have become firmly established in popular consciousness. People may not heed the advice coming at them from the government, the media, the medical profession, but nobody can now be unaware of the key components of what is officially regarded as a healthy life. The huddles of furtive smokers outside ordinary houses as well as public buildings symbolise the ascendancy of preoccupations about health over social behaviour. In this chapter we look at the evolution of some of the key themes in the regulation of lifestyle in the cause...

Concluding Observations

In the previous sections, the committee has outlined what population health means in terms of understanding not only the risks of various exposures to individuals but also the importance of incorporating concepts related to the distribution of risk in populations. This chapter has outlined a way to understand how social, environmental, and biological conditions shape population health. Population-based interventions, such as tobacco control policies, show that it is possible to implement cost-effective strategies that benefit society as a whole and improve the health of many segments of the population. Population health improvements will have to focus attention on both overall improvement in the nation's health and reduction of the disparities in health, as recommended by Healthy People 2010. To achieve this goal, the nation will have to develop innovative strategies for interventions for a broad set of health determinants. Many of the determinants of health are part of the broad...

Retinoblastoma susceptibility gene rb abnormalities in cancer

The rb gene is expressed in all normal tissues and cell lines (Lee et al., 1987b). It is expressed in a mutated form or absent in retinoblastomas (Lee et al., 1987b, 1990 Horowitz et al., 1990). Abnormalities of this gene have been described in several other human tumours, e.g. small cell lung cancer (SCLC) (Harbour et al., 1988 Hensel et al, 1990 Mori et al., 1990). Harbour et al. (1988) found that 13 of primary SCLC and 18 of SCLC-derived cell lines showed structural abnormalities of rb and 60 of SCLC-derived cell lines showed a loss of the gene. Loss of gene expression has been reported in 30 of primary non-SCLCs (Xu et al., 1991) and it appears also from this study that altered rb expression may be related to tumour stage. Inactivation of rb was reported in two bladder cancer cell lines and lack of expression without gross gene deletion in another cell line (Ishikawa et al, 1991). Of considerable interest is the suggestion of rb inactivation with tumour progression. For these...

The Hypertensive Accountant

He denied headaches, palpitations, sweating episodes, muscle weakness, paresthesia, urinary tract symptoms, or any past history of renal or other cardiovascular disease. He was a nonsmoker, drank little alcohol, tried to follow a no-added-salt diet, and had noticed no recent weight change. There was no family history of hypertension. Physical examination revealed a patient of normal weight for height (72 kg and 175 cm) who did not appear Cushingoid. Heart rate was 84 bpm and BP 144 96 lying down and 148 100 standing. Respiratory and abdominal examinations were unremarkable. The apex beat was not thrusting or displaced, there were no signs of congestive cardiac failure, no radiofemoral pulse delay, no renal or carotid bruits, and no abdominal masses, and peripheral pulses were normal. An echocardiogram was consistent with mild left ventricular hypertrophy and early diastolic dysfunction. A chest x-ray was normal.

Phase Ii Metabolizing Enzymes Glutathione Stransferases

Unselected incident cases of pancreatic adenocarcinoma and 146 ethnically matched controls by Liu et al. found no associations between GSTM1 polymorphism and pancreatic cancer susceptibility.54 In a population-based case-control study, conducted in six San Francisco Bay area counties from 1994 to 2001, an association between homozygous deletions of two GST genes, GSTM1 and GSTT1 smoking and pancreatic cancer was analyzed.53 In this population, homozygous deletions of the GSTM1 and GSTT1 genes alone did not affect the risk of pancreatic cancer. An interaction between the GSTT1-null genotype and cigarette smoking was observed, especially among women. Therefore, in this subpopulation, the combination of a deletion polymorphism in GSTT1 and heavy smoking might be associated with an increased susceptibility of pancreatic cancer. It should be noted that subjects for this study were exclusively of the Caucasian population and that ethnic and genetic factors are known to substantially...

Miscellaneous Drugmetabolizing Enzymes

N-Acetyltransferases (NATs) make up another group of drug-metabolizing enzymes. NAT1 and NAT2 are polymorphic and have various xeno-biotics with primary aromatic amine or hydrazine structures as their substrates.78-80 As with GSTM1, Bartsch et al. also found a possible association of NAT1 polymorphism with a modest increase in susceptibility to pancreatic diseases.63 Anderson et al. analyzed pancreatic tissue samples from smokers and nonsmokers for their content of a variety of drug-metabolizing enzymes. They detected low levels of epoxide hydrolase, cytosolic sulfotransferase, and of a variety of CYP enzymes (see Section 7.2). However, the O-acetyltransferase activity of pancreatic cytosols was high, about two-thirds of the levels measured in the human colon. Moreover, cytosols predominantly expressed NAT1.81

Pharmacological Treatments Of Impaired Memory Function

Specificity of drug effects is an issue with cognitive-enhancing drugs in a parallel way to debates on the specificity of cognitive impairing drugs. It is not clear to what extent antidementia drugs produce any specific improvement in memory functions. Sahakian et al. (1993) showed that tacrine improved choice reaction time and improved performance on a task in which patients learnt to follow a simple rule and then reverse this rule. However, it had no effect compared with placebo on any memory task, leading Sahakian et al. to argue that tacrine improved attentional functions. Cholinergic agonists such as nicotine increase the effect of ACh, either directly or by sensitizing the receptor site. There is evidence that AD is associated with a reduced number of nicotinic cholinergic receptors, and that tacrine increases the number of nicotinic cholinergic receptors in AD patients (Nordberg et al., 1992). Subcutaneous nicotine has been shown to improve AD patients' performance on rapid...

Carrying Out Randomisation

Example - delay between randomisation and start of treatment - radiotherapy for inoperable non-small cell lung cancer Although full details are not provided, the delay from randomisation and commencement of radiotherapy (RT) probably resulted in three patients allocated to be treated with two fractions of radiotherapy receiving none in the trial of the Medical Research Council Lung Cancer Working Party (1996). For the 13-fraction option, six received no RT.

Adverse skin reactions to drugs

Intramuscular gold is a well-documented treatment in RA, but its mechanism of action is still poorly understood. Patients given gold salts have a high risk of cutaneous reactions. The mechanisms of cutaneous reactions are unknown and vary according to the molecules (Hofmann et al., 1986 Bonnetblanc, 1996). Smokers, HLA Bw35 patients, and perhaps atopic states are more prone to gold drug reaction. Inflammation at the site of injections is frequent but with no consequence. (Hofmann et al., 1986). Pruritus is frequently observed, more often with oral salts. Exanthemas are common and may disclose an associated visceral disease. Drug hypersensitivity is rare, but severe. Accumulation (chrysiasis) may be observed with long-term treatment (Smith et al., 1995). Chrysiasis is a distinctive and permanent pigmentation of light-exposed skin resulting from the administration of parenteral gold salts (Fig. 6). Focal aggregates of particulate gold are deposited in the reticular and papillary dermis...

TNF Receptors and Trail Apo2L

Recombinant human TRAIL (10 mg kg administered once daily for 7 d) (97). One of the most exciting features of TRAIL therapy is the strong positive interaction effect of TRAIL with chemotherapeutic agents or ionizing radiation. TRAIL treatment has been shown to sensitize tumor cells derived from acute leukemia, breast cancer, lung cancer, colon cancer, prostate cancer, and melanoma to chemotherapeutic agents (98-105). In an in vitro setting, TRAIL has been shown to induce apoptosis in normal primary hepatocytes (106). In light of this observation, it remains to be seen whether TRAIL therapy offers a margin of safety in humans, as is seen in mice and monkeys.

Incidence of Mental Illness

In 1996, a large-scale nationwide mental health and substance abuse epidemiological study was conducted by researchers from the University of Antioquia and the University CES of Medellin. Funded by the Ministry of Health and working with a national team of more than 100 interviewers, the researchers interviewed a random sample of 15,046 individuals older than 12 years of age across the country, using the Clinical Diagnostic Inventory II questionnaire, which is based on the DSM-IV classification. This is the most comprehensive mental health study ever conducted in Colombia. The lifetime prevalence of diagnosable disorders was as follows nicotine dependency, 28 major depression, 19.3 alcohol abuse and dependency (combined), 16.6 posttraumatic stress disorder, 4.5 somatization, 4.3 generalized anxiety, 3.8 and schizophrenia, 1.4 . The lifetime use of marijuana was 7.8 and of cocaine 2.5 (Torres and Montoya 1997). Suicide is also a public health problem in 1995, a total of 58,830 suicides...

Box 165 Mutations Can Happen Without Any Help From Environmental Exposure

Wonder whether people would react differently to the mutagens and cargino-gens in cigarettes if they were labeled on the packet with the sinister sounds of their chemical names. The fact that something is herbal does not mean that it is inherently either safer or more dangerous it only means that it was synthesized by a plant instead of a factory and likely contains a relatively complex mixture of biochemicals. Within that herbal preparation are bio-chemicals that have exactly the same chemical structures and names that they would have if they had been synthesized by a pharmaceutical company. The fact that something has been chemically synthesized does not necessarily mean that it is either more or less likely to be a mutagen it only means that it is a relatively better characterized item that is often less biochemically complex than the same item derived from an herbal source. So the real key to whether something is more or less likely to be harmful or mutagenic depends less on...

Inherited disorders of hdl

There is significant interest in understanding the genetic basis of HDL-C metabolism as HDL-C is inversely associated with CHD, independent of LDL-C levels. Modulating HDL-C metabolism, therefore, has significant potential in the treatment and prevention of coronary disease. Although several environmental factors are known to affect HDL-C levels including cigarette smoking, obesity, physical activity, and diet, it is estimated that at least half of the variation in HDL-C levels in humans is genetic. Yet, to date, we have identified only a few of the genes responsible for inherited syndromes of low or high HDL-C primarily from familial monogenetic disorders with extremes of HDL-C phenotypes. Nevertheless, this basic understanding has already led to the development of novel pharmacotherapies, such as small-molecule CETP inhibitors. The next steps, however, are to further elucidate the details of HDL-C metabolism and identify the host of other genes that may affect HDL-C levels in the...

Considerations for the Use of Mouse Models for Human Cancer

To find more than a single tumor arising from a tissue field. In addition, sporadic cancers in humans arise in a field of normal tissue. In the majority of mouse models described to date, the expression ofthe oncogene and or deletion of the tumor suppressor of interest occurs throughout the tissue, leading to cancerization of the entire tissue field (73). More recently, a mouse model for lung cancer has avoided this problem by relying on spontaneous recombination events to activate expression of the primary oncogene in a small number ofscattered cells in the mouse (33). The increasing sophistication ofgenetic manipulations such as this will continue to increase the effectiveness of mouse models in the study of cancer.

Elevated Fibrinogen Levels

Blood clotting is the final event that blocks the coronary arteries, it's not surprising that studies have implicated elevated fibrinogen levels as a cardiac risk factor. Though fibrinogen levels can easily be tested, at present they aren't routinely measured because there's no known way to bring down high fibrinogen levels. It's also unclear whether reducing levels of fibrinogen would decrease the chance of getting heart disease or having a stroke. In some cases, however, regular exercise, weight loss, and quitting smoking can reduce elevated fibrinogen. Other interventions that prevent excessive blood clotting include taking low-dose aspirin or low-dose alcohol and eating a lot of fish.

Cancerinfiltrated Cervical Lymph Nodes as Part of a Cancer with Unknown Primary

Primary localizations is urgently indicated (e. g. eso-phageal cancer, stomach cancer with Virchow gland involvement, lung cancer with supraclavicular metastases, Pancoast cancer, Schmincke cancer and thyroid gland cancer including the medullary subtype). In addition, malignant paraganglioma with local spread must be taken into account.

Special Subtypes of Ductal Salivary Gland Cancers

Shows cytology of an anaplastic small cell salivary gland cancer metastasis of a small cell lung cancer must be excluded. In lymph node lymphoma must also be excluded using T- and B-cell antibodies and melanoma using S100 protein Ab and HMB45 Fig. 18. Shows cytology of an anaplastic small cell salivary gland cancer metastasis of a small cell lung cancer must be excluded. In lymph node lymphoma must also be excluded using T- and B-cell antibodies and melanoma using S100 protein Ab and HMB45

Cardiothoracic Surgery

CT surgeons are experts on the heart, its complex physiology, and particularly the art of cardiopulmonary bypass. Within the domain of the heart, lungs, and mediastinum, they perform some of the most time consuming, regimented, and physically challenging of all operations. Their patients often leave the operating room in a critically ill state and head to the SICU for postoperative recovery. Surgery of the heart is delicate and fascinating. These surgeons treat conditions like blocked coronary arteries, thoracic aneurysms, and congenital abnormalities. On the thoracic side, they also perform pulmonary resections (e.g., on patients with lung cancer), mediastinoscopy, and bronchoscopy, just to name a few. They also perform esophageal surgery for cancer, achalasia, and other disorders of the esophagus. Fellowship training is typically 2 to 3 years in length. Subspecialty experience in pediatric cardiac surgery and heart-lung transplant is also available.

Interpreting New Medical Information Finding a Doctor Who Matches Your

That each of these studies worked backward, from heart disease to risk factor. The results don't mean that almost everyone with at least one of these factors will develop heart disease. But the results do make a strong case for paying attention to all four of the majors. Although the emphasis of this book is on cholesterol, the others deserve equal focus. If you have high blood pressure, high cholesterol, diabetes, a smoking habit, or any combination of these, focusing on them will help you live better and probably longer. Exercise, healthier eating habits, and getting to a healthy weight can do wonders for high blood pressure, high cholesterol, and diabetes. A variety of drugs can help get these under control and protect against their cardiovascular complications. And various approaches are helping more and more people stop smoking.

Useful Serological Parameters in Confirmation of SCLC

In the attempt to achieve an initial separation between small-cell types (oat-cell, or round-cell subtype) of lung cancer for systemic therapeutic treatment, a serological analysis of neural cell adhesion molecule (NCAM) and neuron-specific enolase (NSE) values can be helpful to confirm small-cell anaplastic cancers or at least to detect this type as a component of the neoplastic lesion. The values obtained in the investigation of 221 cases are listed in Table 2. Table 1. Clinical signs characteristic for different subtypes of lung cancer Table 1. Clinical signs characteristic for different subtypes of lung cancer Subtype of lung cancer

Biography of Gordon Allport

Allport rose to prominence in national circles. He edited the major journal in the field, the Journal of Abnormal and Social Psychology (1937-1948), and was president of the American Psychological Association (1939)- He was one of the founders, in 1936, of the Society for the Psychological Study of Social Issues (SPSSI), an organization that applies psychological insights to practical social issues, and he became its president in 1944. The organization continues to commemorate Allport's memory by awarding an annual prize for a paper on intergroup relations. Allport was one of several U.S. psychologists who assisted intellectuals in Europe to find work in the United States so they could flee Nazi Germany. Another contribution at the time of the war was his effort to help control wartime rumors, reflected in his daily newspaper column and his later book on rumors (Allport & Postman, 1947). He was awarded many professional honors. Gordon Allport died of lung cancer on October 9, 1967,...

Tstaging Supported by FDGPET

FDG-PET is particularly accurate in detecting malignant pulmonary lesions. Lung cancer shows a high uptake of FDG, whereas background activity in the normal lung and mediastinum is generally low. Numerous studies have demonstrated that FDG-PET is the most accurate noninvasive method of detecting and staging lung cancer. The evaluation of solitary pulmonary nodules was one of the earliest applications of FDG-PET for extracranial tumors. Prospective studies have shown that FDG-PET has both sensitivity and specificity of approximately 90 in the evaluation of solitary pulmonary nodules (Coleman 1999 Marom et al. 2000).

Comparisons with Results of CT

Several studies have evaluated the application of FDG-PET for mediastinal staging of lung cancer. The criteria for the analysis of mediastinal lymph node involvement varied between studies. Some investigators reported sensitivity and specificity on a patient basis, while others determined the number of mediastinal sites involved, and still others analyzed the number of lymph node regions involved. Nevertheless, in all studies reported so far, FDG-PET was found to be significantly more accurate than CT for mediastinal staging of lung cancer. Vansteenkiste et al. performed a prospective study of 690 lymph node stations from 68 patients with potentially operable NSCLC (Vansteenkiste et al. 1998). CT correctly identified the nodal stage in 40 patients (59 ), with understaging in 12 patients and overstaging in 16 patients. PET combined with CT was accurate in 59 patients (87 ), with under-staging in 5 patients and overstaging in 4 patients. For detecting locally advanced disease (N2 N3),...

The Doctorpatient Relationship

The ability to listen, understand, explain, advise, and educate are central to the role of an internist. Without strong interpersonal skills, it would be difficult to diagnose an underlying substance abuse problem, help a patient start an exercise program or quit smoking, encourage healthier eating habits, or guide a patient's decision to sign a do-not-resuscitate order and abandon aggressive treatment. Through comprehensive history and physicals, internists spend a great deal of time with their patients talking with them and gaining insight into their lives, their values, and their concerns. Physicians with these qualities will establish lifelong, trusting relationships with their patients.

Special Approaches for Obtaining Specimens for Cancer Diagnosis

Ad a) EUS-FNA Ryan et al. (2001) reported briefly on the methods of lung cancer biopsy. The authors emphasize the possibility of using EUS-FNA biopsy of mediastinal nodes. The sensitivity in the diagnosis of carcinoma in lymph nodes was more than 90 in their own studies, with no complications. Table 15. Comparison of relapse rates after transpleural and transbronchial diagnosis of lung cancer Table 15. Comparison of relapse rates after transpleural and transbronchial diagnosis of lung cancer

Epidemiology how the hazards of industrial chemicals can be detected

The evidence also suggests that workers who smoke and are also exposed to asbestos are much more likely to suffer cancer than those who don't smoke. The incidence of cancer in this group is much higher than the incidence in the smokers and exposed workers combined. This is an example of synergy (where the combined effect is more than additive).

Difficulties in Preoperative SLN Detection and Nstaging

In contrast to breast cancer and melanoma, in the case of lung cancer it is not easy to apply the contrast medium in the area surrounding the primary tumor in the lung. Therefore, it has been necessary to devise new approaches, which include Transthoracic administration of mTc-labeled colloid or contrast media in cases with peripheral lung cancer. Established imaging methods have only a limited impact on the staging of lung cancer. But the aforementioned factors in destruction of the functional structures of the lymph nodes are of little or no interest, because in the middle-aged and elderly in Central European countries and the United States tuberculosis is no longer an important problem and scar formation is also less important than earlier, because of the increasing protection of persons exposed to inhaled fibrosing factors. In addition, the incidence of lung cancers is steadily increasing in the female population. In women of working age scar formation seems to be much less...

Prevention Of Type 2 Diabetes

Post-challenge) Low insulin secretion Insulin resistance syndrome (low HDL-C, high triglycerides, hypertension, fibrinolytic defects, glucose intolerance) Low magnesium level Low chromium level High plasma non-esterified fatty acids Low sex hormone binding globulin Low physical activity Cigarette smoking

PDGFD Chromosomal Localization and Cancer

PDGFD maps near to a human chromosomal locus (11q23-24) of recognized genomic instability (9). This region also encodes matrix metalloproteinases (20) and shows gene copy-number variations in some diseases (e.g., Jacobsen's syndrome, various cancers) that are related to the expression of aberrant growth factors (9,20,21). Of particular interest is the amplification about this locus in glioblastoma multiforme (22) and childhood medulloblastoma (23). Amplifications or deletions in the region of chromosome 11q23-24 have also been implicated in lung cancer (24), ovarian cancer (25), and primary sarcomas (26). Considering the role of PDGFA and PDGFB in malignancy (20,27), it is possible that inappropriate expression of PDGFD might contribute to cancers associated with chromosome 11q23-24 abnormalities.

Definition of the Disease

Breast cancer is the most common nondermatologic cancer in the world, and aside from lung cancer, it is the leading cause of cancer-related deaths among American women. It is estimated that over 200,000 new cases of breast cancer are diagnosed in the United States each year. In addition, approximately 40,000 women and 400 men die annually in the United States from this disease. Risk factors associated with the development of breast cancer include increased age, reproductive history (nulliparous, delayed childbear-ing), early menarche, late menopause, certain genetic mutations (BRCA1 and BRCA2), family history of breast cancer, and exposure to certain carcinogens.1

Differential Diagnosis

Carcinoembryonic antigen (CEA) concentrations are used primarily in gastrointestinal malignancies, particularly colorectal carcinomas. CEA is an antigen present in the fetal colon as well as in cancers. CEA, like CA-125, is a heterogeneic cell surface glycoprotein that is a member of the immunoglobulin superfamily. The function of CEA has not yet been identified. With an upper limit concentration of 2.5 mg L, the sensitivity for identifying early-stage (Dukes A and B) colorectal cancer is 36 with a specificity of 87 . In advanced-stage disease, the sensitivity improves to approximately 80 . False positives can be found in patients with liver disease, smokers, and patients with small bowel obstruction. CEA is useful (if elevated at diagnosis) in detecting recurrence and liver metastasis. It is not a useful screening test because of poor sensitivity and low prevalence. CEA may be elevated in mucinous epithelial ovarian cancers. If CEA is elevated prior to therapy, it may be a useful...

Why carbon monoxide is such a deadly killer

People whose work leads to inhalation of car exhausts (for example, traffic policemen and car mechanics) and people living in houses with a constant low level of contamination, perhaps from a slightly faulty gas fire, can suffer from low-level poisoning. The effects of such long-term exposure are not clear, but it has been suggested that heavy smokers who are exposed to carbon monoxide levels of perhaps 5-10 per cent or more in blood may suffer from effects on the heart. However, cigarette smoke does have many other toxic constituents. Oddly enough, carbon monoxide is actually produced in our bodies in tiny amounts by certain enzymes, but the levels are too low to have any significance.

Transcriptome Analysis Through Expressed Sequences

Two additional techniques, SAGE and microarrays, have been used for investigating transcriptomes in specific cell types, tissues, or particular processes. These techniques have been extensively reviewed and are discussed here very briefly. SAGE (Serial Analysis of Gene Expression) is an innovative technology that has been used widely for transcriptome profiling (Valculescu et al., 1995). In this method, a sequence tag of 10 or more bases is generated for each transcript in the cell or tissue of interest, and those 'unique' tags thereby constitute a SAGE library. Sequencing of the SAGE library creates a transcript profile. The resulting sequence tags are subsequently mapped to the genes, and the expression levels of the genes can be obtained through the counting of the SAGE tags, although it happens quite often that a SAGE tag may correspond to several genes, and some of the genes may not have a meaningful SAGE tag. An improved version of SAGE, called long-SAGE, has been devised, in...

Alcohol our favourite drug

Majority of people probably don't consider alcohol to be a drug or that, like most drugs, it is a potential poison. Alcohol is a drug in the sense that it has particular desirable effects on the body people drink it in order to experience its pleasurable effects. It can also be addictive, and has been responsible for more death, disease, and ill health than any other single drug, with the exception perhaps of nicotine tobacco. The deaths due to alcohol number in the thousands, whereas those due to ecstasy amount to a handful. It is far more of a problem than all the drugs of abuse we tend to worry about, such as heroin and cocaine, because it is accepted by society, having been used by humans for several thousand years. Perhaps society, and politicians in particular, should be as concerned about the drug alcohol as about illegal drugs. There is now increasing concern about the problem of binge drinking among young people and its potential long-term effects as well as the immediate...

Tumor Suppressor Genes Mimic Methylation Patterns in Different Tumor Types

With the progression of the disease, a large number of cancer genes have been reported to carry high level of methylation in a normally unmethylated promoter (33-40) for example, RASSF1,RARbeta,DAPK,p16,p15,MGMT, and GSTP1 in lung cancer, CDKN2A, CALCA, MGMT, and TIMP3p in esophageal cancer, 14ARF in ulcerative colitis, GSTP1 in prostate cancer, HIC-1 and p53 in breast cancer. It is not yet established whether methylation is an initiating event or a secondary event in gene silencing. Irrespective of the role of methylation in the initiation of tumor development, methylation both marks and plays a key role in an epigenetically mediated loss of gene function that is as critical for tumori-genesis as mutations in coding regions.

Research in a vulnerable group trial into the causes of sudden infant death syndrome

It is often argued that the only way to research hypotheses about the bad consequences of risky behaviour is to use observational methods of research, for example, into the hypothesis that living near a busy traffic junction causes asthma in young children, or that smoking cigarettes causes lung cancer, because it would not be ethical to set up an experimental trial by, say, moving some children to live near a busy junction and seeing whether they contracted asthma or not. The fact that there is a concern with the risk of the exposure means that it can only be measured in an observational model. By contrast, the babies' deliberate exposure to 15 oxygen was an attempt to create the environment which the researchers believed may have been the cause of sudden infant death syndrome. The infants were placed in that environment in order to see what the effect was.

Genetic Classification Assists Risk Estimation

So far, the complex issues of interaction between genotype and environment are understood for only a small fraction of genetic diseases. This can make it difficult to sort out the genetic components of many traits that involve phe-nocopies or that may be conditional upon environmental effects, especially if there are many different genes and environmental factors that can affect the trait. Through the studies of geneticists, epidemiologists, and others, the complex interplay of genes and environment is gradually coming into focus. Will this eventually let us pinpoint who will become alcoholics if they take up drinking, or who it is that will develop lung cancer if they take up smoking The goal is to end up being able to offer estimates of altered risk in the presence of environmental effects. Those risk estimates will tell us who has susceptibilities that should lead to more medical monitoring, different treatments, or advice on how we should change our diets or other behavior...

Man with a Tender Toe and Anemia

He was employed and smoked one pack of cigarettes and drank one pint of liquor each day. Preexisting medical problems included hypertension, hypercholesterolemia, and type 2 diabetes, but he did not consistently see a physician or take prescribed medications. Laboratory data from 3 years earlier were notable for hemoglobin 13.9 g dL and creatinine 1.3 mg dL. The gout was treated with an intraarticular steroid injection, hemodialysis was initiated, and hypertension, diabetes, and alcohol and smoking cessation were managed medically. Recombinant human erythropoietin (Epogen) injections were begun for treatment of anemia. He did not require red blood cell transfusion.

Prospective observational epidemiological studies

In the case of physical activity, people who engage in greater amounts of activity may themselves select other healthy behaviors which are incompletely measured and adjusted for (e.g. less cigarette smoking or altered diet). There may also be a genetic component to physical activity, either based on spontaneous activity100 or clustering of other genetic factors which facilitate activity101. Analyses of twin studies have shown contradictory results concerning asso

Mutation Detecting Fish

Mutations arise spontaneously (often as errors during DNA replication, repair, or recombination) at low but consistent rates typically on the order of one in a million gametes per locus per generation. However, many physical and chemical agents, known as mutagens, enhance mutation rates. Among these are ultraviolet light, X-rays, and other high-energy radiations, plus various natural and synthetic chemicals such as nicotine, caffeine, arsenic, cortisone, and mustard gas. Most if not all mutation-causing factors are known to promote human cancers as well. Thus, there are valid reasons for concern when any mutagenic agent reaches high concentrations in the environment. Furthermore, more than 2000 new chemical compounds are introduced each year in an array of consumer products, and it is desirable to know whether any of these might elevate mutation rates appreciably.

Case Study 2 The Penalties of Vice and the Rewards of Virtue

There was no history of exposure to carbon monoxide. Congestive heart failure can occur following an ischemic event. This patient did not, however, have evidence of a previous infarction. His stenosis should not induce CHF. The alcohol is strongly suspected in this case as the cause of the CHF. This suspicion could be greatly enhanced if subsequent abstention from alcohol led to an improvement.

Tobaccoderived Carcinogens 2231 Tobacco Components

There are approximately 69 carcinogens among the nearly 5000 chemical constituents identified in tobacco smoke.45 The three major classes of carcinogens are the tobacco specific nitrosamines (TSNAs) (e.g., NNK and NNN), polycyclic aromatic hydrocarbons (PAH), and the aromatic and heterocyclic amines.45 A smoker who smokes 20 cigarettes per day inhales approximately 9.0 g of NNK per day. Approximately 25 of this carcinogen is rapidly converted to NNAL by red blood cells. We have hypothesized that a portion of these carcinogens can be delivered into the pancreas either via the blood stream or bile. To test this hypothesis, we have analyzed human pancreatic juice for the presence of tobacco-derived compounds and have demonstrated that certain tobacco-derived products, namely cotinine and TSNA, are indeed present in pancreatic juice.55 Cotinine was detected in all analyzed samples of pancreatic juice from smokers and was present in only two of nine samples of pancreatic juice from...

Polycyclic Aromatic Hydrocarbons

Because of inhalation of smoke, especially tobacco smoke, the lungs are the most likely sites of cancer from exposure to PAH compounds. However, these compounds are also found in foods cooked under direct exposure to pyrolysis conditions and are suspected of causing cancer in the alimentary canal. Extraordinarily high rates of esophageal cancer have been observed in Linxian, China, and may be attributable to PAHs from unvented cookstoves.13 In this study, the glucuronide conjugate of 1-hydroxypyrene was monitored as a biomarker of exposure to PAH compounds (Figure 13.11).

Modifiers Of Nnitrosamine Carcinogenesis

Among compounds that have been tested as chemopreventive agents in azaserine- or synthetic N-nitrosamines-induced pancreatic cancers in Wistar rats and in hamsters are methionine91 green tea extracts92 beta-carotene, Vitamin C, Vitamin E, selenium93 phenyl isocyanate94 Oltipraz95 inhibitors of prostaglandin synthesis96 clofibrate97 and caffeine, nicotine, and ethanol.98 The effects of dietary modifications, such as fat type and dose20-22 and caloric restrictions23,99,100 have also been studied (see Chapter 21). Preventive efficacy of several synthetic and naturally occurring compounds, given either alone or in combination, have been tested against NNK-induced lung carcinogenesis. Compounds that inhibited NNK-induced lung tumorigenesis include (p-XSC), nonsteroidal anti-inflammatory drugs, tea and its active polyphenols, aromatic isothiocyanates and their N-acetylcysteine conjugates, myo-inositol, dexamethasone, indole-3-carbinol, aryl alkyls, 4-ipomeanol and its analogs,...

Genetic Alteration In Pancreatic Cancer And Potential Biomarkers

Whether tobacco-derived carcinogens can cause mutations in these genes in the pancreas of humans or animals is currently unknown. Indirect evidence, such as the relatively high proportion of G to A transitions in K-ras in pancreatic cancer and an increased risk for this malignancy in individuals with repair deficiency of the DNA alkylation, suggests the involvement of nitrosamines,139 however, there is no direct proof that this type of damage results from the exposure to tobacco carcinogens. Interestingly, the most common mutations of the K-ras gene in mouse and hamster lung tumors induced by NNK are GGT to GAT transitions in Codon 12.140-144 This type of mutation has been associated with 06-methyl guanine,141 whereas, (NNKOAc), a direct acting pyridyloxobutylating agent, causes GGT to TGT and GGT to GTT mutations in Codon 12 of this gene.140 A higher frequency of K-ras Codon 12 mutations revealing G to T and G to C transversions, as well as G to A transitions in nonneoplastic...

Cathepsin B in cancer invasion

Consistent with the consensus view of a correlation between invasion and the degree of cathepsin B expression, the latter has also emerged as an important indicator of cancer progression. The cathepsins B and L occur in significantly higher levels in tumours of the head and neck compared with corresponding normal tissues (Kos et al., 1995 Budihna et al., 1996) but the levels of expression of the inhibitors stefins A and B were unaltered (Kos et al., 1995), suggesting that tumour tissue contains higher levels of the active forms of the cathepsins. Cathepsin B levels have been found to correlate frequently not only with tumour grade and lymph node metastasis, but clearly also with overall survival and disease recurrence. Luthgens et al. (1993) measured cathepsin B and the inhibitors stefins A and B in the bronchoalveolar lavage fluid (BALF) in lung cancer patients. Cathepsin B levels and that of the inhibitors were substantially higher in BALF from metastasis as compared with squamous...

Issues of Clinical Relevance

John, a 16-year-old boy, was brought to treatment by his mother, who was concerned about her son's habits. She reported that he was reclusive and spent long hours in his room listening to heavy metal music and not participating in family life. She also reported that he wore torn and loose pants. The mother had been born and raised in Nicaragua, was Catholic, and did not agree with all these fads, as she expressed it. On interview, it was clear that John was experiencing a mild depression. He had also begun to smoke marijuana but quit after experiencing two panic attacks. After several weeks of treatment with an antidepressant and psychotherapy, his depressive symptoms remitted, he completely quit smoking marijuana, and his relationship with his parents improved. John reported that even his mother had made changes, becoming more tolerant of his musical choices. He was euthymic at 1-year follow-up.

Cellularlevel and organismlevel definitions

At the single-cell level, the term sensitivity suffices to indicate the ability to react to environmental stimuli and the paramecium is a good example of such biological sensitivity. Even when the organism has a nervous system, reactivity that is undertaken solely in response to one type of external irritation is also normally described as sensitivity. For example, not only do most insects appear to respond directly and blindly to direct stimulation, we commonly use the sensitivity label for animal and human responses in the context of reactions to a finite stimulus a dog that is sensitive to a high-pitched whistle, an ex-smoker sensitive to tobacco smoke, a boy sensitive to poison ivy, a girl sensitive to remarks about her curly hair, and so on. In such contexts, we would

Prevention and Proaction The Path to Optimal Memory

No matter how old you are, it's not too late to take steps to prevent memory loss. In this chapter, I review thirteen strategies for achieving and maintaining optimal memory. Some are good health habits that can reduce the risk of illnesses that might impair your memory as well as the likelihood that you'll need medications with memory-related side effects. Others are strategies that appear to strengthen the brain and enhance cognitive function. Best of all, they're neither expensive nor difficult to carry out. Obtain regular exercise Put out the cigarettes Take vitamins Involve yourself with others Maintain healthful nutrition Aim for a good night's sleep Learn something new Moderate alcohol intake Engage in life Manage stress

Toxins That Attack Synaptic Function

There are many different neurotransmitters in various regions of the nervous system. Usually, each neuron makes and releases only one specific neurotransmitter. Many toxins act on neurotransmitters to interfere with normal synaptic transmission. In this manner these toxins have a neurotoxic action. Following is a discussion of the important neurotransmitter, acetylcholine, and several compounds that affect its action. These include botulinum toxin, nicotine, muscarine, curare, and atropine. Also discussed are biogenic amines as neurotransmitters and the impact of certain drugs of abuse, such as amphetamine, on their activity. Finally, several amino acids serve as neurotransmitters. The actions of strychnine and tetanus toxin as inhibitors of glycine neurotransmitter behavior are discussed as examples of toxins that affect the amino acid type of neurotransmitter.

Atlasbased pathology detection

Callosal Anatomy Although probabilistic systems are under development for the population-based analysis of callosal data (Thompson et al., 1998a), their ability to resolve callosal differences in small groups of subjects with dementia is indicated in Figure 5.7. In one validation experiment (Thompson et al., 1997) (Figure 5.10), probability maps were created to highlight abnormal deviations in the callosal anatomy of a specific subject. The medical history of the subject in question indicated the presence of lung cancer, which had spread to the brain. Two metastatic tumors were present, one in each hemisphere. The first, and larger, tumor (volume 95.2 cm3) was centered in the high putamen of the right hemisphere (see Figure 5.10), while a second tumor

The role ofMMPs and TIMPs in cancer invasion and metastasis

The metalloproteinases, MMP-3, MMP-7 (pump-1), and MMP-10 have been studied in human gastric and colon carcinomas. Of these, only MMP-7 has been found to be expressed in a majority of these tumours and this expression appears to be restricted to tumour cells and is not found in stromal cells or lymphocytes (McDonnell et al., 1991). After an investigation of the expression of MMP-2 in lung cancer cell lines, Zucker et al. (1992) concluded that factors other than MMP alone might be involved in the invasive and metastatic process. This is based on two important observations. They found that high levels of MMP-2 were associated with high tumorigenicity and invasive and metastatic potential of lung cancer cell lines. They then transfected these cells with K-rev-1 which reverts them to a less malignant phenotype. Zucker et al. (1992) noted that the revertants produced MMP-2 at the same levels as the parent cell line, but possessed slightly lower invasive ability and a vastly reduced...

Geneticenvironmental Interaction And Pc

The strongest epidemiologic risk factor for PC is cigarette smoking. It is suggested that a host-environmental phenomenon exists wherein cigarette smoking appears to interact with genetic susceptibility to PC. These findings were based upon a nested case-control study of 251 members of 28 PC-prone families.21 Each family comprised 2 or more members with PC. The effects of smoking, young age of onset within the family, diabetes mellitus, sex, and number standing of affected relatives with respect to the risk of PC were evaluated. Findings revealed that smoking posed an independent risk factor for familial PC, wherein the odds ratio (OR) was 3.7 and the 95 confidence interval (CI) was 1.8 to 7.6. The risk was greatest in males and in family members younger than age 50 (OR 5.2 and OR 7.6, respectively). Furthermore, Smokers developed cancer one decade earlier than nonsmokers (59.6 vs. 69.1 years P 0.01), and the number of affected first-degree relatives also increased risk (OR, 1.4 95 CI...

Phase i clinical trials in solid tumors

Recently, results of a phase I trial by Aghajanian et al. have been published. In this study, 43 patients in a variety of neoplasms were treated with single-agent bortezomib in doses ranging from 0.13 to 1.56 mg m2 dose. The tumor types included were non-small-cell lung cancer (NSCLC), colon, head and neck, melanoma, ovary, renal, prostate, bladder, cervix, endometrial, esophagus, gastric, and unknown primary. A total of 89 doses were administered, with an average of 2 cycles per patient. The median number of previous chemotherapeutic regimens was four. Reported DLTs were diarrhea and sensory neurotoxicity. Other side effects seen were fatigue, fever, anorexia, nausea, vomiting, rash, pruritus, and headache. There was no dose-limiting hematological toxicity. One partial response was seen in a patient with NSCLC. The maximum tolerated dose (MTD) was established at 1.56 mg m2. Pharmacodynamics studies showed a dose-related inhibition of 20S proteasome activity with increasing dose of...

ErbB2 expression in other forms of human cancer

In summary, it would be safe to conclude that the current evidence overwhelmingly confirms the clinical predictive value of this oncogene, in terms of overall survival and of recurrence- and metastasis-free survival. Whether this applies with equal force to other tumour types than carcinomas of the breast is uncertain. Expression and amplification of erbB2 currently appears to possess greater predictive value for breast than for ovarian carcinoma, but the possibility that its expression and or predictive value may not be universally applicable should also be considered. The erbB2 protein is expressed only in non-small cell lung cancer but not in small cell lung carcinoma and, moreover, its expression correlated with lymph node metastasis in squamous cell carcinomas but not in adenocarcinomas (Shi et al., 1992). The significance of such differential expression is still unclear.

Subarachnoid hemorrhage 299

Oral contraceptives also increase the risk of stroke in women under 50 however, the older high-dose pills were far more dangerous than today's low-dose versions. Several studies have suggested an increased risk for low-dose pills, but others have found a significant risk only in women who smoke as well as take the pill. Women who smoke, use birth control pills, and have migraines appear to have an even greater chance of having a stroke.

Genetics of Alzheimers Disease

Reid, R.T., Lloyd, G.K., and Rao, T.S., Pharmacological characterization of nicotine-induced acetylcholine release in the rat hippocampus in vivo evidence for a permissive dopamine synapse, Br. J. Pharmacol., 127, 1486, 1999. 3. Imperato, A., Mulas, A., and Di Chiara, G., Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats, Eur. J. Pharmacol., 132, 337, 1986.

Answers and Discussion

Hypertonicity is expected in nicotine overdose. Q2. (Answer b) A single cigarette has from 10 to 20 mg of nicotine compared to an average cigar that contains approximately twice as much. How can cigarettes be used so extensively if the quantity of nicotine is so near the alleged lethal amount of nicotine of 60 mg Some of the nicotine is lost in sidestream smoke and some is incinerated. Further, the value of 60 mg is probably something of an underestimate. Q3. (Answer b) Children ingesting cigarettes are in danger of slow nicotine absorbtion. Avoid Ipecac because the child might seize from nicotine and aspirate vomitus. Other forms of gastrointestinal decontamination should be attempted. Q4. (Answer b) Cotinine, an oxidized form of nicotine, is generally measured in urine to evaluate a person's smoking status. It is better to measure cotinine than nicotine because only 5 of smoked nicotine is excreted into the urine. Further, the average urinary concentration of nicotine in a smoker is...

Chromium too much of a good thing can be very bad indeed

Those working with chromium compounds are vulnerable to an industrial disease known as chrome ulcers, which was first reported in 1827 among workers in Glasgow, Scotland it became a regular feature in all the industries in which chromates or chromium salts were employed, such as chrome-plating, French polishing, calico printing, and leather tanning. The ulcers would suddenly appear but only after many months of exposure. They were about a centimetre in diameter, and exposed raw flesh which itched unbearably. In industries where workers were breathing chromium-laden dust there could be ulceration of the nasal cavity. The incidence of lung cancer among

Oakland Site Visit October 2001

The committee visited the Oakland Community Voices for Immigrant Health project site in October 2001. The Community Voices project in the city of Oakland, California, is administered by the Asian Health Services and La Clinica de la Raza, two multisite, nonprofit, community-based, federally funded clinics in Oakland. The partnership among these two health care services providers, the Alameda County Health Department, and other community organizations like the Alameda Health Consortium has been fruitful and effective in addressing several of the complex and interrelated issues facing area communities, ranging from a lack of health insurance to tobacco use among minority, disadvantaged populations.

Treatment and Prevention

In individuals without current CHD, the number of risk factors present should be determined and the 10-year risk of CHD calculated using the Framingham scoring system.5 The Framingham scoring system assigns points according to the risk factors present in a patient, and these points are added up to determine a final 10-year risk. The risk factors included in this assessment are cigarette smoking, hypertension (systolic > 140 mm Hg), HDL cholesterol < 40 mg dL (1.0 mmol L), diabetes, family history of premature CHD, and age. Reflecting its protective nature, a concentration of HDL > 60 mg dL (1.6 mmol L) subtracts one point from the risk score.

How do people view risks

Throughout our lives we are exposed to many different hazards and to the various risks associated with them. Every time we drive a car, for example, there is a risk of an accident and therefore of injury or death (which can be calculated). Similarly, other means of travel will have different, but known, risks. Other activities, for example smoking, skiing, skydiving, have known risks of death, injury, or disease. We choose whether or not to engage in these activities and take the risk, even though we may not always appreciate the size of the risk. Most people know that a risk of death or disease from an activity is not a certainty, for example not everyone who drives or travels in a car has an accident and suffers injury at some time in their life. When challenged as to why they smoke someone may answer that their Uncle Fred smoked two packs of cigarettes a day and lived to a good age. They know that it is possible to avoid the effects many suffer, but they choose to take the risk...

Prognostic Values Of Endothelial Progenitor Cells

Smoking was shown to have pleiotropic effects on EPC numbers. Data from animal models associate second-hand smoking to an increase in EPC number, leading to increased tumor angiogenesis in a mouse cancer model 121 . On the other hand, studies examining the level of EPCs in smokers led to complex results, suggesting a dose-dependent effect of nicotine on the level of EPCs that either increases or decreases the number and proliferative potential of EPC 122, 123 . Conversely, physical activity led to increased levels of EPCs, revealing another benefit of exercise in improving cardiovascular health 124, 125 .

Social Security Act Section 1619 453

Smoking Tobacco smoking is harmful not only to smokers but also to those who live or work with them, regardless of HIV status. It has been associated with a higher risk of HIV infection. There are conflicting data on the effects of smoking on HIV disease progression, and the effects of preexisting smoker's leukocytosis (see below) do not seem to be protective. Some studies point to increased risks for certain opportunistic infections in HIV-infected smokers, especially pcp. However, the only infections in which this association has been proved are anogenital abnormalities and cancers. other studies have shown that current smokers are more likely to develop oral candidiasis and oral hairy leukoplakia, but less likely to develop cytomegalovirus disease. Heavy smokers (more than one pack a day) have been shown to be more likely to develop bacterial pneumonia compared with light smokers, nonsmokers, or ex-smokers. Finally, studies have shown that ex-smokers are more likely to develop...

Pulmonary Function And Toxicity

Macrophage cells patrol the alveoli and they also consume particles that have escaped the first line of defense, the cilia and mucus described above. Some toxins, such as tobacco smoke, are deleterious to the body not only directly by organ injury but also indirectly by undermining the normal protective mechanisms. They increase the viscosity of mucus and inhibit ciliary action. Both of these effects limit the organism's ability to capture and eject toxins from the pulmonary system. Some toxins harm macrophage and thereby lead to an increased susceptibility to infection. Some antibody-producing cells are also found in the lungs and they can be effective in resisting infection by antibody synthesis. The type of antibody found in the lung is called secretory antibody and is composed of immunoglobulin A, a protein type distinctly different from the major antibody types found in the blood. Protecting the lung against invasion is so critical that the body has evolved additional mechanisms....

Mental Illness and Substance Abuse

O was found to be overwhelmed with shame, helplessness, hopelessness, and extreme anxiety. She was having fantasies of throwing herself through a window but observed that the windows in the medical ward were too small. Her worries included fear that she would never regain custody of her daughters. In the course of the evaluation, she reported that her girls were all I live for and proudly displayed pictures of them. She had an appointment with the jail social worker, who was helping her get into a drug rehabilitation program. To gain acceptance, she was expected to write a letter stating her goals but reported feeling too overwhelmed to do so. She was also a heavy smoker and having a nicotine fit and bargaining to let her have a smoke. The immediate intervention consisted of helping her prioritize her worries to decrease her anxiety. To regain custody of her children, she needed to participate in drug treatment, so the task of writing her goals letter...

Radiation Oncology As A Palliative Modality

The need for radiation therapy as a palliative measure to make patients feel better is often urgent. For instance, patients suffering from metastatic breast or prostate cancer may develop neurologic symptoms due to the tumor's extension from the vertebral body toward the spinal cord. In this case, radiation oncologists are called in for rapid treatment of spinal cord compression. They are the only specialists who can attempt to reverse quickly the neurologic deficit and prevent paralysis. They also help relieve the symptoms of superior vena cava syndrome, when tumors (usually lung cancer) grow and obstruct the main vessel draining blood from the head and neck into the heart.

Gene Therapy Using PSMA Enhancer

Prostate-specific membrane antigen is tissue-specific that is, PSMA promoter could drive the expression of the luciferase reporter gene specifically in prostate cancer cell lines LNCaP and C4-2, but not other nonprostate cell lines such as breast cancer (MCF-7), lung cancer (H157) and colorectal cancer (HCT8) cell lines in vitro. Expression of suicide gene cytosine deaminase (CD) under the control of the PSMA promoter-enhancer in prostate cancer cells sensitized the cells to 5-fluorocytosine (5-FC) with the inhibitory concentration (IC50) < 300 imol L in vitro. Furthermore, in vivo studies with athymic nude mice carrying transfected to C4-2 cells with the same therapeutic construct (used in in vitro studies) carrying CD gene under regulatory control of the PSMA promoter-enhancer could efficiently sensitize the cells to 5-FC (intraperitoneal injection of 5-FC, 600 mg kg twice a day for 3 wk). All C4-2 cell tumors expressing the therapeutic construct were killed by 5-FC, showing in...

Does wtl expression relate to prognosis in other human tumours

Wtl gene transcripts are not detectable in non-small cell lung carcinoma cell lines and lung cancer tissue (Amin et al., 1995). Loss of heterozygosty at the wtl locus was found in five of 53 cases of non-small cell lung cancer and this was associated significantly with advanced tumour stage and nodal spread. Loss of heterozygosity (LOH) correlated with nodal involvement in the squamous cell carcinoma subtype and patients with tumours with LOH at 1 lpl3 showed poorer survival than those without LOH at this locus (Fong et al., 1994). Bepler and Garciablanco (1994) have identified three other regions at 11 pi3 and lip 15 which suffer somatic loss associated with these tumours, suggesting that these genetic loci might harbour suppressor genes that might be involved with their pathogenesis.

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