The Painless Stop Smoking Cure

Quit Smoking Magic

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Quit Smoking Magic Summary


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Negative Effects Of Tobacco

As early as 1963, tobacco industry officials privately recognized that nicotine was addictive (Glantz & colleagues, 1996). On average, a cigarette puts 1 mg of poisonous nicotine into a smoker's blood a thimbleful of nicotine, a 60-mg dose, would be fatal to adults. Researchers have found that the addictive power of nicotine can produce withdrawal-symptomlike cravings in teen smokers in a matter of weeks. Further, teens frequently underestimate how long and the amount they will smoke. Smoking a pack-a-day costs approximately 1,000 annually. The average smoker spends at least 3,300 per year on cigarettes. Teens must consider both short-term and long-term outcomes of being hooked on nicotine. Tobacco smells cling to smokers hands, clothes, hair and many others strongly dislike the odor. Smokers develop bad breath and frequent coughs. Besides bad breath, smokers experience shortness of breath from reduced oxygen in the blood the reason for this is printed in the Surgeon General's...

Late Phase Ii Clinical Trial Of S1 In Lung Cancer

The objective of this clinical trial was to examine the antitumor activity and toxicity profile of S-1 in patients with stage Illb or IV lung cancer who underwent no treatment prior to the onset of this clinical trial. Sixty-two patients were enrolled in this clinical trial, and 61 patients were treated with S-1. Fifty-nine patients were eligible for the analysis of response and toxicities. S-1 was administered orally at a dose of 40 mg m2, twice daily, i.e., once after breakfast and once after dinner. One course consisted of 28-d consecutive oral administration and of subsequent 14-d withdrawal. This regimen was repeated in four courses unless the disease progressed. Twenty-two patients with stage IIIb lung cancer and 37 patients with stage IV lung cancer were enrolled in this clinical trial. As shown in Table 11, the response rate per protocol set was 22.0 (13 59). As shown in Fig. 15, the median follow-up was 281

Lung Cancer

Lung cancer is the most common neoplasm in the Western world. Management depends on histological type and stage of the disease at diagnosis. Although the tumor is usually diagnosed by bronchoscopy, staging is dependent on various imaging procedures. The prognosis for non-small cell lung cancer (NSCLC) correlates closely with the presence of mediastinal adenopathy. Mediastinal lymph node involvement is reported in 28-38 of patients at the time of diagnosis. Patients with large subcarinal nodes or contralateral adenopathy are considered unresectable. The 5-yr survival for unresectable disease is less than 5 . The current staging system for lung cancer uses EUS is suitable to evaluate common sites of spread of lung cancer such as the mediastinal lymph nodes, left adrenal gland, liver, and direct invasion of the mediastinal structures (esophagus, trachea, great vessels, or heart) by the primary tumor. Over the past decade, EUS has emerged as a valuable adjunct in the evaluation of lymph...


Nicotine is an alkaloid found in tobacco, and is responsible for its pharmacological effects and addiction. Contact dermatitis from nicotine, considered as rare, has been more frequent since its use in transdermal systems. Irritant dermatitis is mainly encountered, as contact urticaria seems to be rare. Allergic contact dermatitis, sometimes generalized, has been reported, with positive patch testing to nicotine base (10 ethanol or petrolatum). No consequences have been reported in patients who start smoking again after skin sensitization. Bircher AJ, Howald H, Rufli T (1991) Adverse skin reactions to nicotine in a transdermal therapeutic system. Contact Dermatitis 25 230-236 Vincenzi C, Tosti A, Cirone M, Guarrera M, Cusano F (1993) Allergic contact dermatitis from transdermal nicotine systems. Contact Dermatitis 29 104-105

Primary Nursing Diagnosis

The treatment of choice for AAA 6 cm or greater in size is surgical repair. When aneurysms are smaller, some controversy exists regarding treatment. Some authorities suggest the smaller aneurysm should just be evaluated frequently by ultrasound examination or CT scan, with surgical intervention only if the aneurysm expands. There is increasing evidence suggesting that beta blockade, particularly propranolol, may decrease the rate of AAA expansion, and blood pressure control as well as smoking cessation is important. Others suggest elective surgical repair regardless of aneurysm size. If the aneurysm is leaking or about to rupture, immediate surgical intervention is required to improve survival rates.

Discharge And Home Healthcare Guidelines

Use extreme caution not to make the patient feel guilty about the cause of the SAB however, it is important that she be made aware of factors that might contribute to the occurrence of an SAB (such as cigarette smoking alcohol and drug usage exposure to x-rays or environmental teratogens). Preconceptual care should be encouraged, should the patient decide to become pregnant again.

Aat Deficiency And Disease

Adult life, particularly in cigarette smokers. 8 The Z variant is prevalent in northern Europeans, with a frequency of about 1.5 in Sweden and Norway, and greater than 2 in Denmark, Latvia, and Estonia. 9 It is extremely rare in Asian and African populations. The Z protein is synthesized normally, but tends to polymerize in The association with pulmonary emphysema is related to cigarette smoking, highlighting an important interaction between genetic and environmental factors. This is thought to arise from the action of neutrophil elastase, a major protease of neutrophils released during an inflammatory state. Deficiency of AAT, its major inhibitor,

Conclusions And Recommendations

Although certain exposures significantly increase the risk of developing esophageal SCC, the overall prevalence of this disease should be considered when deciding who might benefit from endoscopic screening. It is probably a combination of factors that conveys the highest risks, and physicians must determine on an individual basis whether screening endoscopy might have a potential impact on a given patient's course. For instance, an impoverished 60-yr-old black man with a long history of alcohol and tobacco use may benefit from a screening endoscopy with iodine chromoendoscopy, whereas a wealthy 60-yr-old nonsmoking white woman who drinks alcohol only occasionally is unlikely to dervie any benefit from screening. Others who may benefit include patients with an early-stage head and neck cancer or patients from a region of the world where the incidence of esophageal SCC is very high. Only patients who can be effectively treated for esophageal cancer should be screened, although early...

Age of Cancer Incidence

The fifth section discusses how carcinogens alter the incidence of cancer at different ages. The best data on human cancers come from studies of people who quit smoking at different ages. Longer duration of smoking strongly increases the incidence of lung cancer. Interestingly, among nonsmokers, the acceleration of cancer does not change as individuals grow older, whereas among smokers, the acceleration tends to rise in midlife and then fall later in life. I also discuss incidence data from laboratory studies that apply carcinogens to animals. These studies show remarkably clear relationships between incidence and dose. Dose-response patterns provide clues about how mechanistic perturbations to carcinogenesis shift quantitative patterns of incidence.

Many Roles Many Rewards

The professional rewards of a career in epidemiology are the excitement of discovery and the knowledge that epidemiologic studies can be used to help people improve or maintain their health over time. Epidemiologic research has significantly improved the public's health over the past century. Research results have been used to identify new medicines to treat disease, to educate the public about the health effects of cigarette smoking and inactive lifestyles, and to improve sanitation and water treatment, significantly reducing the burden of infectious disease in heavily populated areas. see also Gene and Environment Population Screening Public Health, Genetic Techniques in Statistical Geneticist.

Heritability in Humans

Percent of their genes) are more likely to be alcoholics than the fraternal twins of alcoholics (who share only about 50 percent). Adoption study data suggest that the risk for developing alcoholism for adopted children is influenced more by whether their biological parents were alcoholics than whether their adopted parents are alcoholics, suggesting that genes contribute to alcoholism more than environment. Similar but less extensive data has been collected for nicotine addiction. Very little genetic epidemiological data has been collected for illegal drugs. The only genes that have been conclusively shown to affect susceptibility to addiction in humans are genes that encode proteins responsible for the metabolism of alcohol. In the body, ethanol (drinking alchohol) is oxidized by enzymes to acetaldehyde and then to acetate. Certain alleles of aldehyde dehydrogenase genes that are common in some populations, such as Asians, lead to increased levels of acetaldehyde when alcohol is...

Preconceptual counselling in the lowrisk setting

It is worth enquiring about the health of the male partner. Smoking cessation programmes are more available now and there has been concern about the smoking in male partner and miscarriage risk 12 . Regardless of this risk, it would be a clear advantage for the father to not smoke and the incentive of a healthy environment for the child may help smoking cessation. Occasionally fathers are on medication which may have implications for fertility and review of such medication may be worthwhile.

Why are clinical trials unreliable for the detection of rare adverse events

When a new compound intended for chronic or life-long use is introduced into the market, approximately a few hundred patients will have been treated for one year or longer. If the agent is an inhaled steroid for treatment of asthma, a lipid-lowering statin, or an antihypertensive drug, one can assume that the medications will be prescribed for longer than one year, maybe even for decades. Thus, one could legitimately question whether the one-year experience with the compound is adequate to predict drug safety over 5, 10, or up to 30 years. Many serious adverse events may take several years to become apparent. For example, it may take more than a decade of tobacco use to cause lung cancer. A safety profile based on limited drug exposure is inadequate and can be very misleading.

Factors Such As Charge That Affect Drug Absorption Distribution And Excretion

Charged drugs or other molecules do not readily pass through lipid membranes. However, this often leads to the mistaken conclusion that drugs that are strong acids or bases, i.e., mostly ionized at physiological pH, will not be absorbed from the gut or pass the blood-brain barrier. If a drug is a strong base and has a p a of 9.4, the ratio of ionized to un-ionized will be 100 1 at pH 7.4, but that still means that approximately 1 of the drug is un-ionized and free to go through a lipid membrane. And there is always about 1 that is un-ionized because the equilibrium is virtually instantaneous therefore, the effect of the drug being a strong base or acid is that it decreases the effective concentration available to diffuse across the membrane. This slows the rate of diffusion but not the ultimate amount absorbed given adequate time for absorption. With absorption from the gut, the surface area is quite large and transit time in the small intestine, where most absorption occurs, is...

Breast Cancer and Its Treatment

It is the second leading cause of cancer death among women (representing 15 of all cancer deaths), compared to 25 of cancer deaths from lung cancer (American Cancer Society ACS 2004). Estimated deaths from breast cancer in 2003 were 39,800 for women and 400 for men. Mortality rates for breast cancer declined significantly in recent years, mostly among young women, both white and black, falling 1.4 annually in 1989-1995 and then at a rate of 3.2 annually. Survival for women with breast cancer varies as a function of the stage of the disease at diagnosis. The ACS data show 5-year relative survival rates of 86 for all stages, 97 for local, 78 for regional, and 23 for distant (or metastasized) Breast cancer is the leading type of new cancer among women. The ACS estimated that 211,300 new cases of invasive breast cancer would occur among women and 1300 among men in the United States in 2003 (ACS 2004). New cases of breast cancer represented one third of...

Gender Ethnicracial And Life Span Considerations

Thromboangiitis obliterans, a causative factor for arterial occlusive disease, typically occurs in male smokers between the ages of 20 and 40. Arterial insufficiency usually occurs in individuals over 50 years of age, and is more common in men than women. PAOD affects 20 of people over 70 years of age in the United States. Ethnicity and race have no known effect on the risk of most arterial occlusive diseases.

Goals Of Clinical Trials

This is a randomized, parallel-group trial to demonstrate that the one-year survival of the patients with pretreated advanced (Stage IIIB IV) non-small-cell lung cancer (NSCLC) receiving the oral investigational drug is not inferior to those receiving intravenous (IV) docetaxel.

Treatment Of Malignant Esophagorespiratory Fistulae

TEFs occur in approx 5-15 of patients with esophageal cancer or other mediastinal malignancies. Primary esophageal cancer and lung cancer constitute more than 90 of all malignant TEF, with the vast majority of TEF owing to cervical esophageal cancer (99). Once a TEF develops, the general condition of a patient declines rapidly owing to recurrent aspiration, life-threatening pneumonia, and severe malnutrition. The goal in managing such patients is to achieve rapid and successful palliation whereas minimizing inpatient hospitalization, cost, and complication rates (64).

Sage Uses In Human Genome Mining And Annotation

Lung Cancer SAGE was also used to analyze the transcriptome of non-small cell lung cancer comparing with normal lung tissues. One of the overexpressed genes in this tumor type was the PGP9.5 transcript. This gene was detected in over 50 of primary tumors and cell lines, and advanced tumors were more likely to overexpress PGP9.5 (26). PGP9.5 is a ubiquitin hydrolase normally expressed in the neuroendocrine cells of the bronchial epithelium. A yeast two-hybrid screening approach was used to identify potential PGP9.5 interacting proteins. Among the interacting proteins, the RAN-BPM, ubiquitin-conjugating enzyme (UBC9), and Jun activation domain binding protein 1 (JAB1) genes were identified. The JAB1 was originally identified as co-activator of c-Jun, and recently it was shown to promote the degradation of p27kip1. It was observed that JAB1 and PCP9.5 co-localize in cell perinuclear and nucleolar regions. The investigators speculated that this complex may contribute to the degradation...

Habit Learning and Synaptic Plasticity

Long-term potentiation (LTP) of the strength of corticostriatal connections can readily occur in vivo (104,105) and stimulation of dopamine neurons recently has been shown to modulate corticostriatal synaptic strength in direct correlation with behavioral reinforcement (106). Although LTP can involve a host of cellular and subcellular mechanisms, especially in early phases (107), the persistent substrate for much synaptic plasticity is generally believed to be structural changes in synaptic connectivity patterns (108-110). It is likely that the persistent effects of addictive drugs on habit learning are also ultimately manifested through altered structural patterns of synaptic connectivity (1). Repeated doses of amphetamine, cocaine, morphine, and nicotine can all provoke dendritic growth and synaptic change in rat ventral striatum and PFC (111-114) conversely, removal of striatal dopamine causes broad decreases in measures of synaptic connectivity (115-118).

Phase IV cardiac rehabilitation

Phase IV CR is the long-term maintenance of risk factor modification, with long-term follow-up in primary care. For the benefits of physical activity and lifestyle change to be sustained, the available evidence suggests that both need to be maintained (SIGN, 2002). As clinically indicated, referral to specialist clinicians, such as smoking cessation or psychological support, may still be required (DoH, 2000). This stage is likely to be the most informal stage of cardiac rehabilitation, where there is long-term maintenance of individual goals and monitoring of clinical issues and risk factor modification, mainly by the primary healthcare team (BACR, 1995). It is important that the patient is aware of the exact nature of the follow-up system available.

Exogenous Sources of Advanced Glycoxidation End Products

Tobacco smoke is another exogenous source of AGE. Tobacco curing is essentially a Maillard browning reaction, as tobacco is processed in the presence of reducing sugars. Combustion of these adducts during smoking gives rise to reactive, toxic AGE formation (39). Total serum AGE, or AGE-apolipoprotein (apo)-B levels have been found to be significantly higher in cigarette smokers than in nonsmokers. Smokers and especially diabetic smokers have high AGE levels in their arteries and ocular lenses (40).

Interindividual Variability and Polymorphism

Allelic variants, which arise by point mutations in the wild-type gene, are the source of interindividual variation in the CYP activity. Amino acid substitutions can result in an increase or more commonly a decrease in CYP activity. Environmental factors known to affect CYP levels include medications (e.g., barbiturates, anticonvulsants, rifampin, tro-glitazone, isoniazide), foods (e.g., cruciferous vegetables, charcoal broiled beef), social habits (e.g., alcohol consumption, cigarette smoking), and disease status (diabetes, inflammation, viral and bacterial infection, hyperthyroidism, and hypothyroidism.5 Due to recessive inheritance of gene mutation, some CYP enzymes can be absent or poorly expressed in a certain percentage of the population leading to increased pharmacological response or toxic effects of drugs.26-28 The two major polymorphically expressed enzymes are CYP2C19 and CYP2D6. The poor metabolizer phenotype of CYP2C19 is found in 2-3 of Caucasians and African-Americans...

Transmission Across Synapses

The cholinergic receptors present on skeletal muscles and in autonomic ganglia are activated by nicotine and are blocked by the antagonists tubocurarine and hexamethonium. On the other hand, cholinergic receptors on many end organs are activated by muscarine and are blocked by the antagonist atropine. Thus, these receptors are referred to as nicotinic-cholinergic and muscarinic-cholinergic receptors, respectively. Nicotinic-cholinergic ACh, nicotine

Effects of maternal drug ingestion

Infants of mothers who take drugs such as opiates, cocaine, amphetamines, barbiturates, benzodiazepines and some other medical drugs may develop a withdrawal syndrome with irritability, poor feeding, apnoea and fits. The babies of mothers who have high alcohol or nicotine intake may also exhibit withdrawal. Wherever possible the mother and baby should be kept together in many cases breastfeeding in not contraindicated. If a history of maternal drug abuse was known antenatally a plan of management can be agreed before birth and a referral to the social work team may be appropriate. Management of a baby at risk of drug withdrawal involves careful observation and skilled nursing. If withdrawal is severe treatment with opiates may be required. Naloxone should never be given to infants at risk of opiate withdrawal as it can provoke convulsions. Many labour wards no longer stock nalox-one for fear it will be given inadvertently to an infant of a substance-abusing mother.

Cerebrovascular Accident

In an embolic CVA, a clot is carried into the cerebral circulation, usually by the carotid arteries. Blockage of an intracerebral artery results in a localized cerebral infarction. Hemorrhagic CVA results from hypertension, rupture of an aneurysm, arteriovenous malformations, or bleeding disorder. Risk factors thought to cause blood vessel changes that cause vessel walls to be more susceptible to rupture and hemorrhage include elevated low-density lipoprotein (LDL) and lowered high-density lipoprotein (HDL) levels, cigarette smoking, and a sedentary lifestyle.

Cluster Randomized Designs

The fundamental theory of the classic experimental design by Fisher (1947) is based on the fact that the randomization unit is the same as the analysis unit used as the experimental unit for statistical inference. Statistical inference based on the principle of randomization unit being the analysis unit is hence the most efficient in the sense that it produces the maximum power and requires the minimum sample size. Almost all clinical trials for evaluation of therapeutic intervention have adopted such a principle. For example, subjects such as patients or normal volunteers mentioned throughout this book are not only the unit of randomization but also a unit of statistical inference. However, on the other hand, for assessment of nontherapeutic interventions such as lifestyle intervention or new educational program for smoking cessation, randomization may be easily performed and trials can be efficiently implemented to reduce bias through randomization of some social intact units such...

Evidence From In Vivo Studies With Humans

A cross-sectional study of smokers (N 30) and nonsmokers (N 30) showed a significant inverse relationship between chromosome aberrations and blood folate status and that smoking and blood folate status are interrelated in their association with chromosome fragility. In this study of ex vivo expressed DNA damage, the cells were cultured in low folate medium and the results may therefore reflect the expression of fragile sites within chromosomes (25). A cross-sectional study on buccal mucosal folate and vitamin B12 and its relation to micronucleus frequency in buccal cells revealed that buccal mu-cosal folate and vitamin B12 are significantly lower in current smokers than in noncurrent smokers (29). Although current smokers in this study were three times more likely to have micronucleated buccal cells, this chromosome damage index was not associated with localized folate and vitamin

Epidemiology and aetiology

Cigarette smoking Other factors associated with an increased risk of ectopic pregnancy are previous pelvic surgery, history of infertility, in utero diethylstilbestrol (DES) exposure, strenuous physical exercise and cigarette smoking. The risk of ectopic pregnancy among black women and other ethnic minorities is 1.6 times higher than the risk among white women in the United States 5 .


Phenotyping using caffeine showed no difference in CYP1A2*1F metabolic activity between different genotypes in nonsmokers but a significant difference in smokers homozygous for the A allele compared with the other genotypes in terms of a 1.6-fold increased activity.1-17-1 Unexpectedly, another study demonstrated a lower in vivo activity in patients with colorectal cancer than in healthy controls. 19

The Muscarinic Acetylcholine Receptor mAChR

Before going any further it is important to make a distinction between acetylcholine's muscarinic and nicotinic actions. These two completely different effects are due entirely to the interaction of ACh with different receptors. This is a striking example of the importance of receptors in neural membranes. Acetylcholine's nicotinic action is shown at the junction between motor neurons and skeletal muscle, in some central synapses and as we shall see (spectacularly) in the electric organs of electric fish. It is an action which can be mimicked by nicotine - hence the nomenclature. Muscarinic synapses, on the other hand, are found on smooth muscle and cardiac muscle, and outnumber nicotinic synapses in the brain by a factor of 10-100. Muscarinic synapses are not affected by nicotine but can be activated by muscarine.

The Mthfr Gene Product MTHFR

More recently, Dekou et al. reported that the frequency of the MTHFR 677T allele of the coronary heart disease high-risk town of Dewsbury was significantly higher than in the coronary heart disease low-risk town of Maidstone and was associated with increased total homocysteine plasma concentrations (21). This effect was seen in men but not in women and was not observed for MTHFR 1298A C. Furthermore, a higher susceptibility for malignant lymphoma has been observed in individuals with the combined MTHFR 677CC 1298AA genotype, as well as those with the MTR 2756GG genotype (22). Moreover, the MTHFR 677C T mutation, smoking, and folate status were strong interactive determinants of high-risk adenomas of the colorectum (23). In this study, the risk was particularly high in smokers with low folate and the MTHFR 677CT or the MTHFR 677TT genotype, and in smokers with high folate and the MTHFR 677CC genotype. This risk pattern was also observed for colorectal hyperplastic polyps. Together,...

Learning from the Mistakes of the Past in the Development of Natural Products

Indeed as a direct result of this additional research, Taxol was recommended as a candidate for preclinical development in 1977. Further work demonstrated strong activity against human tumor xenograft systems and stimulated hope of efficacious performance in the clinic. Taxol's mechanism of action was elucidated in 1979, formulation work completed, and toxicology studies started in 1980 32, 100 . With the completion of nonclinical studies, approval was given for entry into phase I clinical trials in 1983 28, 141 . The early clinical trials raised serious issues of toxicity. Indeed, further development of Taxol was almost discontinued. The problems, however, were determined to be related to the poor solubility of Taxol in aqueous systems and the necessity for a high dose, when compared to other antineoplastic agents of the time. The development of a suitable formulation required the use of Cremophor EL, a polyethoxylated castor oil derivative, which created a whole new...

Ovine Pulmonary Adenocarcinoma

OPA is a naturally occurring lung cancer of sheep that has been reported in most sheep-rearing countries. It is absent from Australia and New Zealand and has been eradicated from Iceland. The disease is characterized by a progressive respiratory condition caused by the growth of the lung adenocarcinoma. The tumor appears to originate from two types of differentiated epithelial secretory cells of the distal respiratory tract, the type II pneumocyte and the Clara cell, which retain their phenotype (Figure 5). OPA is invariably fatal once the disease is diagnosed, and affected sheep die as a result of compromised respiratory function caused by tumor enlargement or from secondary bacterial infections. The incubation period of the naturally occurring disease can be very long lasting several months to years.

Future Perspectives

Small ruminant betaretroviruses are a fascinating group of viruses with unique characteristics that are of broad interest through their veterinary, comparative medical and biological importance. The veterinary importance arises from the economic impact in many sheep rearing countries of the diseases induced by JSRV and ENTV combined with the absence of any effective control tools or mechanisms. Their comparative medical interest stems from the striking similarity of some forms of human lung adenocarcinoma to OPA, which is considered an excellent outbred large animal model for these tumors with opportunities to investigate issues that are not available from other systems. Lung cancer is the main cause of death among cancer patients and effective therapeutic strategies are greatly needed to improve patient survival and well-being. OPA is a large animal model that can identify and test the efficacy of new therapeutic interventions in a highly reproducible system.

Mainstream drugs from edible plants

The interference of dietary nicotine (3a) in studies of exposure to environmental tobacco smoke has long been debated. Nicotine is widely distributed, and has been found in twelve plant families, with detectable amounts in many food plants. Thus, levels up to 100 (xg kg have been measured in aubergines, and also non-solanaceous vegetables like cauliflower can accumulate nicotine (Domino et al, 1993). The dietary intake of nicotine is unlikely to produce any direct pharmacological or toxicological effect. For comparison, a cigarette contains on average 8 9 mg nicotine, 1 mg of which is delivered to the circulation of the smoker (Benowitz and Henningfield, 1994). This amount corresponds to the consumption of 10 kg of unprocessed aubergine or 20 kg of pureed tomatoes, and a dietary addition to nicotine is clearly inconceivable. Nevertheless, the amount of nicotine to which passive smokers are exposed can be comparable to that of dietary origin. The possibility therefore exists that...

Otitis Media Introduction

Otitis Media (OM) is an infection of the middle ear most common in infants and toddlers during the winter months. It may be either viral or bacterial. Inflammatory obstruction of the eustachian tube causes accumulation of secretions in the middle ear and negative pressure from lack of ventilation. The negative pressure pulls fluid and microorganisms into the middle ear through the eustachian tube resulting in otitis media with effusion. The illness usually follows a URI or cold. The older child runs a fever, is irritable, and complains of severe earache, while a neonate may be afebrile and appear lethargic. The child may or may not have a purulent discharge from the affected ear. Myringotomy is a surgical procedure performed to equalize the pressure by inserting tubes through the tympanic membrane. The tympanostomy tubes remain in place until they spontaneously fall out. Most children outgrow the tendency for OM by the age of 6. There is a higher incidence in children exposed to...

Randomized Phase Ii Designs

One of the reasons causing variation of tumor response rates is the inherent heterogeneity of cancer. For example, it is extremely difficult to evaluate tumor response of patients with prostatic, brain, or pancreatic cancers. On the other hand, for advanced colorectal cancer, advanced non-small-cell lung cancer, or advanced hepatocellular carcinoma, survival can be observed in a relatively short period of time. In such situations, survival rather than tumor response rate may be used as the primary endpoint for ranking and selection in the randomized phase II cancer clinical trials. As a new agent may not exist under which survival function is uniformly higher than those of all others across time, it is not clear how to define the best treatment based on observed survival functions. Liu et al. (1993), under the assumption of the Cox's proportional hazards model, suggested the use of hazard ratios for

Genetic Considerations

Mutations in the SERPINA1 gene cause alpha-1 antitrypsin (AAT) deficiency. The gene (AT1) causes the hereditary form of emphysema. AT1 protects the body from being damaged by the protinase trypsin. AT1 is inherited in an autosomal co-dominant pattern, meaning that two different gene alleles are expressed and both contribute to the development of the trait. The M allele is most common and results in production of normal levels of AT1. People who are homozygous normal have copies of the M allele from both parents. The two variants (S and Z) cause production of low or moderately low amounts of AT1. Persons with the ZZ or SZ genotype will probably develop AT1 deficiency. Persons with an MS or SS genotype usually produce enough alpha-1 antitrypsin to protect the lungs. There is an increased risk of AT1 for those who carry the MZ alleles, particularly if they are smokers. Familial factors predisposing to emphysema in the absence of alpha-1 antitrypsin deficiency are also likely.

Epidemiology in Food and Nutritional Toxicology

Some examples of human epidemiological studies used in food and nutritional toxicology include linking aflatoxin B1 with liver cancer, food colors with allergic reactions, and prevention of lung cancer by carotenoids. Although links or correlations can be obtained by using epidemiological tools, the major disadvantage of epidemiological studies is the variety of things humans are exposed to, making it difficult to isolated effects of a specific substance on a population. Also, variability in population will affect the outcomes of epidemiological studies. Although epide-miological studies have limitations, they often can be used to corroborate the results of animal-based experiments.

Analytical strategies

An intervention study is a type of prospective study that can be very conclusive as well as very expensive. In intervention studies, the epidemiologist intervenes with the study population, e.g., smokers given a pill containing vitamin E, vitamin C, and beta-carotene to test the effect of supplemental antioxidants on the incidence of lung cancer. Thus, the investigator exerts a degree of control over the risk factors of interest, i.e., intakes of antioxidants.

Molecular epidemiology

Confounding is the effect of a third variable that influences the exposure-disease relationship under study and is very important in epidemiology. The confounder variable is associated with the exposure being studied and is an independent risk factor for the health outcome under analysis. A cohort study on the relation between alcohol intake and risk of lung cancer might find a relative risk. However, people who consume alcohol often smoke (a confounding variable). Smoking is a known risk factor for lung cancer. Confounding variables usually have a stronger effect than the exposure under study. To find the correct relative risk of alcohol on lung cancer, either the study population has to be restricted to nonsmokers or else smokers and nonsmokers have to be separated. Therefore, a corrected estimate of the relative risk can be obtained by calculating a weighted average of the stratum-specific relative risks for smokers and nonsmokers, which usually involves statistical procedures to...

Impact Of Fish Analysis In Different Research Areas

A small number of studies have addressed the possible effects of lifestyle factors such as smoking, air pollution, and caffeine and alcohol consumption on sperm aneuploidy frequencies. Robbins et al. 22 found a significant association between caffeine and alcohol consumption and increased disomy frequencies for some chromosomes. No significant association was noted for smoking. Two studies found a significant association between smoking and aneuploidy for some chromo-somes, 23,24 but it is difficult to rule out combined lifestyle factors because smokers also consume more caffeine and alcohol than nonsmokers. Our laboratory studied over 600,000 sperm cells from heavy smokers, light smokers, and nonsmokers (all nondrinkers of alcohol) and found a significant increase of disomy only for chromosome 13, but not for chromosome 21, X, or Y. 25,26 Perreault et al. 26 studied seasonal air pollution and found an association between high levels of air pollution and YY disomy in nonsmoking men....

Illustrative Examples

Breast cancer remains the most common cause of cancer among women in the United States, and it results in more deaths from cancer among women than any other type of cancer, except lung cancer. Over 40,000 women die from breast cancer in the United States each year. A long history of research, now coupled with the new information emerging from the field of molecular genetics, is beginning to explain the basic steps leading to breast cancer, and it will enable the development of novel treatment and prevention strategies.

Lack of Autoimmunity After Innate Overactivation A Role for Interferons and the Nervous System

As discussed, autoimmune responses are induced similarly to an immune response against pathogens. Both involve an early phase of innate immune activation followed by the activation of adaptive T and B cell responses. It is noteworthy that innate immunity may be overactivated to a state resulting in suppression rather than priming of T cells. Interestingly, some clinically acute infections such as measles virus infection show a phenotype of early severe inflammatory disease and immunosuppression later. Measles patients frequently suffer from superinfectious bacterial pneumonia and often fail to react with a delayed type hypersensitivity (DTH) reaction to intradermal tuberculin protein, a classical type IV immune response according to Coombs 53 . In mice, measles virus leads to intense activation of macrophages and dendritic cells that finally results in an overactivated state associated with increased apoptosis and failure to prime T cell responses 54,55 . Consistently, an infection...

Proposed Pathogenesis Of Gists

The expression of c-kit can be seen in multiple different cell types including the interstitial cells of Cajal (ICC), mast cells, hematopoietic stem cells, melanocytes, germ cells, skin basal cells, and small-cell lung cancer (29). The ICC are a complex network of cells within the GI muscle layers that serve as a pacemaker system that regulates gut motility (30). Immunohistochemical studies have shown that the ICC stain positive for c-kit and CD-34 and are phenotypically similar to GISTs (31,32). These observations led to the hypothesis that GISTs originate from the ICC or evolve from a pluripotential stem cell line from which the ICC also develop (32).

Policies in the United States

Historically, inhumane animal use has been most common in science fairs. These are extracurricular competitions in which junior- and senior-high-school students exhibit their projects. Humane standards at these fairs have been lacking in the past. In the 1960s and 1970s, the Animal Welfare Institute (AWI) reported on many student projects that treated animals cruelly. Typical were projects that involved failed attempts of surgical procedures on monkeys, rabbits, and other species, guinea pigs who were forced to inhale nicotine fumes until they died, and mice* who were given known toxic agents (such as cleaning fluid) to demonstrate their death. Frequently these teenagers worked in their home basements or garages, and they often won prizes for their efforts. What was particularly troubling was that these students were becoming insensitive to animal suffering and learning all the wrong lessons about how to treat animals from these school-sanctioned activities.

Cancer Causing Chemicals

In retrospect, it was fortuitous that soot was acknowledged as one of the first carcinogenic agents. Soot is a complex mixture of chemicals that arises from the combustion of organic material. As scientists and physicians separated soot's individual components, it became clear that chemicals called polycyclic aromatic hydrocarbons (PAHs) were among its principal carcinogenic compounds. The story became even more intriguing when it was shown that many PAHs behave as procarcinogens. Procarcinogens do not cause cancer per se, but they can be converted to active carcinogens by enzymes located in organs like the liver and lung. The implications of this discovery are noteworthy. For example, cigarette smoke contains a wide variety of procarcinogenic PAHs that are turned into active carcinogens in lung cells. Since smokers draw these PAHs deep into their lungs with each inhale on a cigarette, one reason that cigarette smoking correlates so highly with the induction of lung cancer becomes...

Tobacco Related Diseases

GSTM1 and GSTT1 have been particularly studied as risk candidates for tobacco-related cancers. 14,15 While some studies show significantly increased risk for GSTM1*0 and GSTT1*0 homozygotes, others have not replicated these findings prompting the use of meta-analysis. For example, analysis using 43 studies indicates that GSTM1 null is not associated with increased lung cancer risk and that there is no evidence for an interactive effect between the genotype and tobacco consumption.1-15-1 Analysis of 31 studies of the influence of GSTM1, GSTT1, and GSTP1 polymorphisms on head neck cancer risk found modest associations (odds ratio about 1.30) between risk and GSTM1 null and GSTT1 null with greater risk (odds ratio 2.06) associated with combinations of the genotypes. 14 Analysis of six studies also failed to identify significant associations between GSTM1 null and colorectal cancer

Lung Tumor Collection Processing And Models

Lung Cancer Models Lung cancer models that are representative of human cancers are valuable tools to study tumor progression and discovery of therapeutic targets, provided they represent the tumor genotypically and not just phenotypically. While the significance of tumor suppressors (p53, pRB, p16INK4a) and activated oncogenes, such as K-ras and c-myc, involved in lung cancer is well known (8,9,11), the progression model and order of inactivation or activation mechanisms involving tumor suppressors and oncogenes is poorly recapitulated in current lung cancer models. However, some progress has been made in this nascent field. For example, overexpression of activated H-ras using the calcitonin-calcitonin gene-related peptide (CGRP) promoter induces pulmonary neuroendocrine (NE) cell hyperplasias and thyroid tumors (33). This was surprising, as NE lung cancers such as SCLC typically do not have ras mutations. Recently, Linnoila et al. developed a mouse model of lung NE tumors (34). In...

Results From Expression Profiling Studies Of Lung Carcinomas Reveals Distinct Adenocarcinoma Subclasses

It is of considerable interest to determine if a molecular classification recapitulates the existing histopathological classification of lung tumors and reveals previously undiscovered tumor classes. The existing classification of lung cancer as SCLC and NSCLC, and the subclassification of NSCLC, provides us with a framework for evaluating the significance of molecular classification of lung cancers (29-31). Transcriptional fingerprinting by microarray analysis of human lung tumors offers a wealth of information quite rapidly that was previously difficult to obtain. A key issue in lung tumor diagnosis is the discrimination of a primary lung tumor from a distant metastasis to the lung as the clinical course or treatment of the disease may differ from primary lung cancer. In our study (29), microarray analysis readily defined extra-pulmonary metastasis with non-lung expression signatures among putative lung adenocarcinomas, suggesting that expression analysis may serve as a diagnostic...

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All three studies (29-31) observed expression of genes associated with detoxification and antioxidant properties that were highly expressed in a set of adenocarcinomas and mostly in squamous cell tumors. These genes include glutathione peroxidase, glutathione S-transferase, carboxylesterase, and aldo-keto reductase. Their presence in squamous cell lung cancers, which are usually centrally located in the lung and associated with tobacco smoking, may reflect a response by the bronchial epithelium to carcinogenic insults. Validation of expression profiling results is needed at different levels. At one level, it is necessary to know if the profiling data agrees with actual transcript levels in the tissue studied. In the case of lung cancer classification data, Nacht et al. noted that SAGE data were comparable to oligonucleotide probe array and quantitative PCR results for several genes (31). As expression data are noisy, it may be necessary for lung expression profiling data to be...

Novel Insights From Comparing Tumor Profiling With Clinical Response Correlation Of Patient Outcome With Putative

Clustering can classify tumors into distinct groups. Garber et al. (30) identified clusters based on the similarity of transcriptional profile (30). We also identified clusters using a similar approach as well as on the basis of stable clusters identified by combining clustering methods and bootstrapping of tumor samples (29). With our dataset, we asked whether lung cancer patient outcome correlated with the subclasses of lung adenocarcinomas defined. However, such clusters may or may not correlate with clinical end points. For example, in our dataset, there was no detectable difference in prognosis between the primary lung adenocarcinomas and the metastases to the lung of colonic origin. However, in our dataset (29), the NE C2 adenocarcinomas were associated with a less favorable survival outcome than all other adenocarcinomas (Figs. 3A and 4B). The median survival for C2 tumors was 21 mo compared to 40.5 mo for all non-C2 tumors (p 0.00476). When only stage I tumors were considered,...

Medical Applications of Hair Analysis

A number of investigators have applied hair testing to detect prenatal drug exposure (61-70). The retrospective power of hair analysis allows, at the time of birth of an infant, an assessment of drug intake for as long a portion of the gestation period as the length of the mother's hair specimen permits. The first example of determining prenatal drug exposure by hair analysis, reported in 1987, was that of a mother who had ingested PCP during her pregnancy (61). This study and that of Grant et al. (66) demonstrated that determining the pattern of drug usage over the term of the pregnancy by segmental hair analysis may be especially useful in evaluating effects on neurodevelopmental outcomes of varying levels of drug use during specific trimesters. Callahan et al. (67), in comparing hair, meconium, and urine analyses for identifying cocaine use in mothers, found hair and meconium (when performed by GC-MS) to be about equivalent, whereas urine was about half as effective. The Hospital...

Pharmacologic Highlights

The nurse's role is one of monitoring and support. Support the patient who is experiencing symptoms from any rhythm disturbance. Maintain the patient's airway, breathing, and circulation. To maximize oxygen available to the myocardium, encourage the patient to rest in bed until the symptoms are treated and subside. Remain with the patient to ensure rest and to allay anxiety. Discuss any potential precipitating factors with the patient. For some patients, strategies to reduce stress or lifestyle changes help limit the incidence of dysrhythmias. Teach the patient to reduce the amount of caffeine intake in the diet. If appropriate, encourage the patient to become involved in an exercise program or a smoking cessation group. Provide emotional support and

Description Surgical Tracheostomy for Face

Cancer of the larynx is more common in men than in women (5 1 ratio) because, heretofore, men have been more likely to smoke cigarettes and drink alcohol, but the incidence in women is rising as more women also smoke and drink. Cancer of the larynx occurs most frequently between the ages of 50 and 70. Women are more likely to get laryngeal cancer between the ages of 50 and 60 and men between the ages of 60 and 70. Laryngeal cancer is 50 more common in African Americans than in whites. HISTORY. Be aware as you interview the patient that hoarseness, shortness of breath, and pain may occur as the patient speaks. Obtain a thorough history of risk factors alcohol or tobacco usage, voice abuse, frequent laryngitis, and family history of laryngeal cancer. Obtain detailed information about the patient's alcohol intake ask about drinks per day, days of abstinence, and patterns of drinking. Ask the patient how many packs of cigarettes he or she has smoked per day for how many years.

Clinical Description And Prevalence

The incidence of melanoma is rising faster than all other cancers except lung cancer in women, currently varying between 5 (Western Europe) and 20 (Northern Europe) to over 50 (Queensland, Australia) cases per 100,000 per annum. 1,2 Familial clustering of melanoma was first described by Norris in 1820, 3 but it was not until the second half of the 20th century before others documented the familial occurrence of melanoma. Across several population-based studies, 1-13 of melanoma cases reported the occurrence of melanoma in at least one first-degree relative. 4 Hence, it is commonly accepted that melanoma predisposition is hereditary in 10 of all cases. But even in high-sun-exposure areas such as Queensland, Australia, less than 5 of melanoma probands report two or more first- or second-degree relatives affected with melanoma. 5

Carcinogen Dose Response

Lung cancer incidence increases with roughly the fourth or fifth power of the number of years (duration) of cigarette smoking but with only the first or second power of the number of cigarettes smoked per day (dosage). The stronger response to duration than dosage occurs in nearly all studies of carcinogens. Peto (1977) concluded The fact that the exponent of dose rate is so much lower than the exponent of time is one of the most important observations about the induction of carcinomas, and everyone should be familiar with it and slightly puzzled by it First, in examples such as cigarette smoking, the onset of carcinogen exposure does not begin at birth but at some age t0 at which smoking starts, so the duration of exposure is t - t0 - t. Cigarette Smoking The classic study of cigarette smoking among British doctors estimated annual lung cancer incidence in the age range 40-79 as I(t) c(1 +d 6)2r4 5, where c is a constant, d is dosage measured as cigarettes per day, and t t -10 is...

CIS1 Cytokine Inducible SH2Containing Protein

The CIS1 gene is located in the distal region of mouse chromosome 9, which is linked to Trf, Gnai2, and Col7aI (25). This region shares homology with the short arm of human chromosome 3 (3p21), so that the putative CIS1 locus in human is thought to be 3p21. It is known that the human 3p21 locus is frequently lost or rearranged in renal cell carcinoma and lung cancer (31,32). In view of the function of CIS1 and its tissue distribution, loss of the CIS1 gene may thus constitute one of the mechanisms involved in unregulated cell proliferation.

DescriptionSurgical Major Chest Procedures

Rate remains approximately 41 , and the 5-year survival rate is 15 . Only 16 of lung cancers are found at an early, localized stage, when the 5-year survival rate is 49 . The survival rate for lung cancer has not improved over the last 10 years. There are two major types of lung cancer small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Sometimes a lung cancer shows characteristics of both types and is labeled small cell large cell carcinoma. Both types have the capacity to synthesize bioactive products and produce paraneoplastic syndromes such as the syndrome of inappropriate antidi-uretic hormones (SIADH), Cushing's syndrome, and Eaton-Lambert syndrome of neuromuscu-lar disorder. SCLC accounts for 13 of all lung cancers and is almost always caused by smoking. SCLC is characterized by small, round to oval cells generally beginning in the neuroendocrine cells of the bronchoepithelium of the lungs. They start multiplying quickly into large tumors and can spread to the...

Cessation of Carcinogen Exposure

Lung cancer incidence of continuing smokers increases with approximately the fourth or fifth power of the duration of smoking (Doll and Peto 1978). By contrast, incidence among those who quit remains relatively flat after the age of cessation (Doll 1971 Peto 1977 Halpern et al. 1993). In 1977, Richard Peto (1977) stated that the approximately constant incidence rate after smoking ceases is one of the strongest, and hence most useful, observational restrictions on the formulation of multistage models for lung cancer. Peto argued that, in any model, the observed constancy in incidence after smoking has stopped suggests that smoking cannot possibly be acting on the final stage of cancer progression. There could, for example, be a particular gene or pathway that acts as a final barrier in progression and resists the carcinogenic effects of cigarette smoke. In 2001, Julian Peto (2001) reiterated Richard's argument The rapid increase in the lung cancer incidence rate among continuing...

Multiple Bilayer Membranes

Vinblastine (Figure 1) is a mitotic inhibitor isolated from the plant Catharanthus roseus G. Don. (Apocynaceae). It is used clinically in the treatment of leukemia and Hodgkin's disease, breast carcinoma, Wilm's tumor, Ewing's sarcoma and small-cell lung cancer, either alone or in combination with other chemotherapeutic agents 1 . Vinblastine enters into animal cells by diffusion through the plasma membrane. The permeability of the membrane depends upon the molecular order and thus the mobility of the membrane lipids

Choosing the method of abortion

The anti-progestogen mifepristone is used in combination with prostaglandin doses to achieve medical abortion. There are few contraindications to medical termination and they include suspected ectopic pregnancy, chronic adrenal failure, long-term steroid use, haemorrhagic disorders, treatment with anticoagulants, known allergy to mifepristone or misoprostol, smokers over 35 with ECG abnormalities and breastfeeding women. Medical abortions require to be performed in hospitals or premises registered for abortion. The patient attends briefly to take the mifepristone dose and attends subsequently for day-patient admission, usually 36 to 48 h later. It is customary for legal reasons to supervise the swallowing of the mifepristone tablets, but side effects are trivial and the women can leave after 10 min. Women may bleed slightly in the 48 h following the mifepristone dose and, particularly at early gestations, a very small number may miscarry. The route of prostaglandin administration and...

How the Environment Is Involved in Complex Disease

Genes are not the only things that can affect a complex trait. Often environmental factors can also be involved. The type of environmental factors can be very different for different traits. One obvious example of this is lung cancer. Smoking cigarettes greatly increases the risk of developing lung cancer. Smoking also seems to have an effect on other diseases, including some eye diseases (such as age-related macular degeneration). However, not every chronic smoker will develop lung cancer or eye disease The presence of particular alleles of susceptibility genes is also a risk factor, as discussed below. Other environmental factors, which may be more difficult to identify directly, can still be identified by measuring other risk factors, such as gender, age, occupation, level of education, use of alcohol, and other measures of lifestyle. For example, the effect of estrogen may not be measured directly, but could be identified by finding an effect of gender on the risk of developing...

Class Discovery And Correlates Of Disease Histology

There is now clear evidence that tumors of different histology from specific anatomic sites may often be discerned by their molecular profiles. For example, in lung cancer, clustering algorithms readily enable the distinction between squamous, large cell, small cell, and adenocarcinoma (43,44). Ono et al. (19) have assessed the molecular profiles of ovarian carcinomas with mucinous or serous papillary histologies using cDNA arrays comprised of 9121 distinct human genes. Using the Mann-Whitney test, the authors reported significant differential expression of 115 genes between histological subtypes. The identity of the genes do not readily pin-point a major underlying biological theme related to the distinction between the histological subtypes, and it is somewhat surprising that genes known to be differentially expressed, such as the mucin, MUC-2 (45), were not identified by this analysis. However, additional studies with these genes and their encoded proteins may reveal biologically...

Major Depression And Tissue Composition Studies

Symptoms (Ellis et al., 1977 Fehily et al., 1981), unfortunately these studies lacked diagnostic specificity, did not control for alcoholism or smoking, and did not specify the use of psychotrophic medications. Following those initial reports, eight studies have reported that lower concentrations of n-3 fatty acids in plasma or red blood cells (RBCs) predicted depressive symptoms (Adams et al., 1996 Maes et al., 1996 Peet et al., 1998 Edwards et al., 1998a Edwards et al., 1998b Peet et al., 1999 Maes et al., 1999 Hibbeln et al., 2000). Adams et al. (1996) were the first to report that lower measures of DHA in the phospholipids of red blood cells (r 0.80, p < 0.01) and a greater aracidonic acid (AA) to EPA ratio (r 0.73, p < 0.01) predicted more severe depressive symptoms. Edwards et al. (1998) carefully controlled common confounding factors that would alter omega-3 status among depressed subjects by controlling for both alcohol consumption and cigarette smoking while also...

Results from Twin Studies of Other Disorders and Conditions

The twin study method has been used to try to determine the extent of genetic or environmental influence on a wide variety of traits and conditions. Among these are sense of humor, which appears to be largely environmentally determined, as MZ and DZ pairs have similar concordance. Examples of other diseases in which MZ concordance exceeds DZ concordance, suggesting a significant genetic component, include addictive behaviors such as cigarette smoking and alcohol drinking, mental illnesses such as schizophrenia, as well as stroke and certain types of high blood pressure. Twin studies of many other disorders are ongoing.

Who gets pelvic inflammatory disease

Differences in behaviour have been linked to the risk of PID. A clear association can be seen between vaginal douching and PID but more recent longitudinal studies suggest that douching does not cause PID - rather it would appear that the vaginal discharge and menstrual irregularities associated with PID may themselves lead to more douching 2 . Women who smoke are at higher risk of PID but it is unclear whether this is a marker for sexual high-risk behaviour or a direct effect of smoking itself.

Nitric oxide and the development of atherosclerosis

All the major cardiovascular risk factors (including hypertension, high levels of low-density lipoprotein LDL cholesterol, tobacco use, and hyperhomocysteinemia) are associated with decreased endothelium-dependent vasodilation prior to the development of clinically apparent vascular disease. This would suggest that the endothelial damage is implicated in the development of atherosclerosis (35).

Individual Variability

Epidemiological evidence indicates that vitamin A is protective against lung cancer. Exposing rats to PCB, DDT, and dieldrin significantly reduced the stores of vitamin A in the liver. However, vitamin A can be toxic at high levels. On the other hand, p-carotene, which is a precursor of vitamin A, is fairly nontoxic. Vitamins E and C are both important antioxidants. Lipophilic vitamin E acts to protect the membranes from free radicals and

Tubal factor infertility

The principal cause of tubal disease is pelvic inflammatory disease (PID) which may occur spontaneously or as a complication of miscarriage, puerperium, intrauterine instrumentation and pelvic surgery. A single episode of PID carries up to 10 risk of future tubal factor infertility. The risk is aggravated by further infections due to Chlamydia trachomatis or Neisseria gonorrhoeae. Chlamydia is now the most common sexually transmitted disease (STD) in Europe and responsible for at least 50 of identifiable cases of PID. Due to its silent nature, most affected women give no prior history of chlamydia infection, although three quarters of them have anti-chlamydial antibodies in their serum. Factors associated with chlamydia infection contribute to an increased risk of tubal disease. These include multiple sexual partners, young age at first intercourse, poor socio-economic status, heavy alcohol consumption and cigarette smoking. Opinion on previous

Might There Be Deleterious Consequences of Introducing DNA Hypomethylation in the Genome As a Cancer Therapy

The DNA methylation inhibitors 5-azacytidine, 5-aza-2'-deoxycytidine (decitabine), and 5,6-dihydro-5- azacytidine have been used as cancer chemotherapeutic agents in clinical trials on various neoplasms, including refractory acute leukemia 89 myelodysplastic syndrome 90 advanced non-small cell lung cancer 91 malignant mesothelioma 92 accelerated or blast phase of chronic myeloid leukemia 93 advanced ovarian or cervical carcinoma 94,95 malignant melanomas and colorectal, head and neck, and renal carcinomas.96 For solid tumors, usually little or no clinical efficacy and often no disease stabilization was seen, but many toxic effects were observed.89,91,94-9 Combination therapy on malignant mesothelioma, which showed a low response to 5,6- dihydro-5-azacytidine alon,92 did not improve the response rate (17 ) and increased the toxicity.97 There has been considerable attention recently to testing the efficacy of treatment of high-risk myelodysplastic syndrome (MDS) with 5-azacytidine or...

Spectrum Somatic Mutations in Retinoblastomas and Other Tumors

It is possible that all retinoblastomas have mutations in both alleles of the RB1 gene. RB1 gene mutations have also been identified in several other tumor entities including osteogenic sarcoma and small cell lung cancer. The spectrum of somatic mutations comprises that of germ-line mutations with two important additions

Multidrug Resistanceassociated Proteins Mrps

The family of MRPs is another group of ABC transporters, so far consisting of nine members. Among these members, MRP1, MRP2, and MRP3 have been characterized in some detail in terms of their capability of conferring MDR and their possible physiological functions148 and so will be the focus of this discussion. The founding member of this family, MRP1, was cloned in 1992 from the resistant human small cell lung cancer cell line,149 which does not overexpress P-glycopro-tein.150-153 Subsequent transfection studies demonstrated that overexpression of this 190 kDa membrane protein can confer MDR on a number of natural product anticancer agents such as the anthracyclines, vinca alkaloids, and epipodophyllo-toxins by causing the active efflux of these cytotoxic agents from cells and thus lowering their intracellular concentrations.154-157 Later, MRP2 (cMOAT) and other members were also identified and characterized to varying extents.158-167 Among these MRPs, MRP3 is the member most closely...

Clinical Use of Carotenoids Antioxidative Protection versus Prooxidative Side Effects

Carotenoids are natural pigments, which are found in bacteria, algae, fungi and plants, but which are not synthesized in animals. Animals and human beings get carotenoids through food. If we think on carotenoids, we think mostly on P-carotene, lycopene, lutein, zeaxanthin, and some others. But, meanwhile 600 to 700 carotenoids were identified. About 60 of them are components of our nutrition. Almost ten percent of all carotenoids in mammals can be metabolized to retinol, which is vitamin A, and can therefore function as vitamin A precursors. Carotenoids and retinoids act as antioxidants, influence the growth of the organism, immunologi-cal functions, the visual cycle, and modulate gene expression, too. Epidemiological data have strongly linked higher levels of carotenoid intake and increased circulating and tissue concentrations of carotenoids with reduced risk for various cancers, cardiovascular disease, and other diseases, even clinical intervention trials did not find...

Membrane Bound Complement Regulatory Proteins and their Expression on Tumors

MCRPs are virtually expressed on all cell types and most of tissues. Strikingly, mCRPs are also overexpressed on many tumor cells, including adenoma (Koretz et al. 1992), breast cancer (Madjd et al. 2004), cervical cancer (Simpson et al. 1997), colorectal cancer (Inoue et al. 1994), gastric cancer (Kiso et al. 2002), glicoblastoma (Junnikkala et al. 2000), hepatoma (Spiller et al. 2000), kidney cancer (Magyarlaki et al. 1996), leukemia (Jurianz et al. 2001), lymphoma (Takei et al. 2006), lung cancer (Sakuma et al. 1993), malignant endometrial tissue (Murray et al. 2000), malignant glioma (Shinoura et al. 1994), melanoma (Weichenthal et al. 1999), neuroblastoma (Chen et al. 2000), ovarian cancer (Bjorge et al. 1997), osteosarcoma (Pritchard-Jones et al. 2005), pancreatic carcinoma (Schmitt et al. 1999), prostate cancer (Babiker et al. 2005), and thyroid

Effects of calcium dobesilate on expression of adhesion molecules ICAM1 and VCAM1

Vascular cell adhesion molecule-1 (VCAM-1) is also an important marker of the endothelial function. Similarly to ICAM-1, the concentration of its soluble form (sVCAM-1) is elevated in diabetes and diabetic retinopathy (Nowak et al., 2008, Clausen et al., 2000). The influence of calcium dobesilate on the levels of sVCAM-1 and sICAM-1 was investigated in a clinical trial in mildly obese male smokers. Endothelial dysfunction in these subjects was confirmed by means of increased levels of sVCAM-1, sICAM-1 and related parameters, but no effect of calcium dobesilate on levels of cell adhesion molecules was observed after 3 months of treatment with with 1000 mg calcium dobesilate dobesilate daily(Schram et al., 2003).

Incidence Of Drug Use And Abuse

According to the latest press release of Monitoring the Future's national, annual survey on adolescent drug use (Johnston & colleagues, 2003), alcohol, cigarettes, and marijuana are the leading substances used by adolescents in the United States. Alcohol is the substance most cited by 8th, 10th, and 12th graders 46 , 66 , and 77 , respectively, report lifetime use (i.e., having ever used). Tobacco is the second most commonly reported substance lifetime prevalence for adolescents has declined significantly but is increasing again with heavy marketing to this age group. Despite similar declines in use since the mid-to-late 1990s, marijuana is still the leading illicit drug cited by adolescents, with 18 of 8th graders, 36 of 10th graders, and 46 of 12th graders reporting lifetime use. Rates of ecstasy use rose steadily among adolescents through the mid-1990s and reached peak rates in 2001, with 5 , 8 , and 12 of 8th, 10th, and 12th graders, respectively, reporting lifetime use....

Mechanisms Of Action Of Insecticides

The acetylcholine receptor also can be deactivated to cause the same type of hyperexcitation. Indeed, nicotinoids (which include naturally occurring nicotine analogues and their modern derivatives, sometimes called neonicotinoids), such as imidacloprid, are known to directly activate the acetylcholine receptor, just like acetylcholine. Nicotine's excitatory action is well known. Neonicotinoid derivatives readily penetrate the insect's body and nerve sheath, arriving at critical sites of neurons, and persisting there long enough to exert a powerful excitant effect.

Antitumor mAb Therapy and mCRPs on Tumors

The application of humanized anti-tumor mAbs as a targeted therapy holds great clinical promise and has become more widely used in clinical practice (Adams and Weiner 2005). For example, anti-CD20 mAb (rituximab) has been used for B-cell non-hodgkin's lymphoma (Weiner and Link 2004). Anti-52 mAb (alemtuzumab) is approved for the treatment of chronic lymphocytic leukemia (Faderl et al. 2005). Anti-her-2 neu mAb (trastuzumab) is a humanized mAb against human epidermal growth factor receptor 2 and has been used in metastatic breast cancer patients (Leyland-Jones 2002). Anti-epidermal growth factor receptor mAb (anti-EGFR mAb, cetuximab) has been approved for colorectal and lung cancer (Ross et al. 2004). In addition, numerous humanized mAbs are in different phases of clinical trials, including anti-carcinoembryonic antigen (CEA) for gastrointenstinal cancer (Stein et al. 2005), anti-epithelial cell adhesion molecules (EpCAM) for colorectal cancer and others (Liljefors et al. 2005 Ruf et...

Transtheoretical Model

The Transtheoretical Model (TTM) was originally developed to understand behaviour change related to smoking cessation (Prochaska and DiClemente, 1983), but has since been applied to exercise behaviour (Prochaska and Marcus, 1994). Interventions based on the TTM have been effective in

Supercritical Fluid Extraction

In addition, commercial activity or interest has been reported at over thirty companies including some end users of the technology, equipment suppliers and engineering companies. The activity is generally in the areas of extraction of spices, essential oils, oils and fats, cholesterol, flavours, pharmaceutical materials, and in supercritical fluid chromatography. All these process applications illustrate the wide range of applications of extraction with supercritical fluids in process industries. Excellent compilation for the use of supercritical fluid extraction are published from time to time. These give the status of the technology viz., laboratory scale, pilot plant scale or commercial scale. Brunner and Peter (1982), Randall (1982), Paulitis et al (1983) have presented some of the earlier exhaustive reviews. Koerner (1993) has given a listing of the pilot plants and commercial plants for supercritical fluid extraction. Table 1 highlights the use of supercritical fluid extraction...

Utilitarian Assessment of Animal Experimentation

Moreover, when determining the gains relative to the cost of animal experimentation, we must include not only the costs to animals (which are direct and substantial), but also the costs to humans (and animals) of misleading experiments. For instance, we know that animal experiments mislead us about the dangers of smoking. By the early 1960s, researchers found a strong correlation between lung cancer and smoking. However, since efforts to induce lung cancer in nonhuman animal models* had failed, the government delayed acting.

Ecology and Epidemiology

In Northern Europe, HFRS as well as the carrier rodents exhibit peaks in 3-4 year cycles, while in Central Europe the HFRS incidence follows the fluctuations of'mast years', that is, the abundance of beech and oak seeds for the hantavirus-carrying rodents. In Central Europe, HFRS peaks in the summer whereas in Northern Europe most cases occur in late autumn and early winter, from November to January. Risk factors for acquiring hantavirus infections and HFRS include professions such as forestry, farming, and military, or activities such as camping, and the use of summer cottages. Cigarette smokers and males are more likely to be infected than are females. In the Americas, the increased precipitation during El Ni o Southern Oscillation in South and North America has been suggested as the main reason for the peaks in rodent population densities and for the consequent increased number of HPS cases.

Applications of RNA Phages Three Hybrid Assay

A more medically orientated set of applications has also been developed. For instance, it is known that viruses present defined epitopes to the immune system of their hosts. If those epitopes are common and unchanging, the immune response that occurs after an initial infection will render the host immune to further infection by that particular virus. Many viruses however constantly alter their outer protein surfaces presenting differing epitopes to the immune system, thus escaping immune neutralization. However, modern structural immunology techniques can identify conserved functional domains sequences within these viral proteins that cannot be altered without also causing the virus to lose the ability to replicate or assemble. Raising immune responses against such refined constant epitopes leads to potent vaccines against a range of human and animal pathogens. In fact, work in this area has shown that the immune system is particularly well evolved to recognize repeated copies of...

Clinical Significance

Like the adverse effects of thiazides on glucose metabolism, their effect on plasma lipids is reversible. Therefore, discontinuation of thiazides and use of alternative agents which either lower (e.g., ACE inhibitors, calcium channel blockers) or do not change plasma cholesterol should probably be used for treatment of hypertension in patients with preexisting hypercholesterolemia or combinations of other risk factors such as diabetes, left ventricular hypertrophy, and cigarette smoking.

Beneficial Effects of High Carotenoid Nutrition

Various epidemiological investigations and clinical intervention studies demonstrate clearly the beneficial preventive effects of sufficient-carotenoid and high-carotenoid nutrition. An intervention study with increased vegetable nutrition was carried out with 23 healthy male non-smokers aged 27 to 40 years 34 . The aim of the study was to find out if a high-vegetable nutrition prevents or at least reduces a damage of DNA and especially an oxidative damage of DNA. Following a two-weeks vegetable-free nutrition the participants of the study were fed with 330 ml tomato juice with 40 mg lycopene daily during the third and the fourth week, with 330 ml carrot juice with 22 mg P-carotene and 16 mg a-carotene daily during the fifth and sixth week, and finally with 10 g spinach powder with 11 mg lutein, all solved in water or milk during the seventh and eighth week. Every week the degree of DNA damage of circulating lymphocytes was analyzed. The defined enrichment of nutrition with tomato,...

Model Of Youth Violence

Bushman and Anderson (2001) noted that the public is often misinformed about the status of the scientific evidence on media violence. Bushman and Anderson (2001) documented ways in which media accounts of scientific studies failed to reflect the growing body of evidence and increasing scientific certainty that media violence has a deleterious effect on children. The authors also showed that the correlation between violent media and aggression is equal to or stronger than many other widely agreed upon medical findings, such as the finding that smoking leads to lung cancer or that calcium consumption leads to increased bone mass. Although defenders of the entertainment industry sometimes argue that media violence is simply a reflection of violence in the world, studies demonstrate that television shows and movies tend to present an unrealistically high rate of violence and to portray unrealistically positive consequences of violence. There is a more recent body of research accumulating...

Supplementation of Carotenoids for Prevention and Treatment

Sume carotenoid containing supplements every day. The aim of such supplementation should be to use the protective functions of carotenoids against the development of macular degeneration, cardiovascular diseases, irradiation induced skin aging, and cancer. Even many people followed the change from the principle An apple a day keeps the doctor away in Five servings a day keep the doctor away and use at least five servings of fruit and vegetables, billions of other people and also of those using lots of fruits and vegetables additionally take supplements with p-carotene or retinol or lycopene or other carote-noids 1 . The supplements as nutraceuticals are combinations of different compounds or single compounds. It is always written on the packages how many percentages of the recommended daily amount (RDA) the intake of one tablet or capsule will cover. With high probability billion of people take in supplements with beneficial effects for their health conditions. Nevertheless,...

Selected Issues in Clinical Development

It is to be hoped that new medicinal treatments will, by virtue of their being effective, have a measurable impact on health-related QOL (Fig. 8.38). Historically, the basis for new drug approval has accepted this hope as a reality by implicitly assuming that when biological evidence of efficacy exists, there will be health-related benefits to the patient. QOL end points, either as add-ons to a traditional efficacy study or as free-standing studies, have become increasingly important in supporting comparative product claims and drug pricing and reimbursement. QOL is not, however, necessarily different from efficacy. QOL may serve as basis for approval. The best examples of this are in the area of oncology. Traditional biological oncology end points, such as tumor response and time to event variables (especially survival), have historically served as bases for new drug approval. Although FDA Oncology Division guidances over the past 20 years have invoked QOL end points as an acceptable...

Miscellaneous Mediastinal Processes And Mediastinal Masses Of Unknown Origin

Of thoracic specialists was asked to decide the course of evaluation if EUS-FNA had not been available and this diagnostic strategy was compared to the actual clinical course of events after EUS-FNA. For patients known to have lung cancer before EUS-FNA, 18 out of 34 patients (53 ) demonstrated mediastinal involvement as N2 N3 disease. All of the 18 malignant EUS-FNA diagnoses were recorded as true positive. In 16 patients with known lung cancer EUS-FNA of the suspected mediastinal lesion demonstrated the mass to be benign. Fourteen patients went to either thoracotomy and or mediastinoscopy. Two patients had a positive lymph node, one adjacent to the esophagus, and the other in the aortopulmonary window. The two remaining patients had documented invasive or metastatic disease by other studies. Of 50 patients with unknown disease, EUS-FNA demonstrated media-stinal malignancy in 36 of these patients (72 .) In three patients, benign diseases (sarcoidosis, mediastinal abscess, and...

Carotenoid Degradation Products May Inhibit or Activate Enzymes

Previously genotoxic effects of P-carotene degradation products were found 61 . In in vitro-experiments which were carried out with rat liver mitochondria respiratory functions of mitochondria were compared in presence and in absence of carotenoid degradation products. All carotenoid degradation products which were investigated were able to inhibit the ADP-stimulated respiration - already at lower micromolar range 62 . The lower micromolar range in vivo can only be reached under conditions of heavy oxidative stress. Thus, from experiments with mitochondria the hypothesis was concluded, that at drastic oxidative stress such as in heavy smokers and asbestos workers, a high-dosage supplementation of P-carotene (as high as in CARET- und ATBC-studies) can induce the risk of toxic effects of P-carotene degradation products 62 . In contrast to this potential toxicity at mild oxida- Figure 6. Hypothesis on the usually antioxidative protective role of -carotene and the potential harmful...

Sex Differences in Incidence

Figures A.13-A.18 show the male female ratios for the major adult cancers. The plots highlight two kinds of information. First, the values on the y axis measure the male female ratio, with positive values for male excess and negative values for female excess. The scaling is explained in the legend of Figure A.13. Second, the trend in each plot shows the relative acceleration of male and female incidence with age. For example, in Figure A.13, the positive trend for lung cancer shows that male incidence accelerates with age more rapidly than does female incidence, probably because males have smoked more than females, at least in the past. Positive trends also occur consistently for the colon, bladder, melanoma, leukemia, and thyroid. Negative trends may occur for the pancreas, esophagus, and liver, but the results for those tissues are mixed among locations. Simple nonlinear curves seem to explain the patterns for the stomach and Hodgkin's, and maybe also for oral-pharyngeal cancers.

Topical Intake of Carotenoids and Recommendations

The results on increased mortality and incidence in lung cancer in two large clinical intervention studies with heavy male smokers, who possibly already developed first stages of cancer and the contrast of these findings to p-carotene effects in healthy non-smokers were reasons to investigate mechanisms of potential toxicity of high-dosage supplementation. Furthermore, these results initiated to rethink recommendations of p-carotene intake, especially to think over recommendations for maximal intake. International experts and the scientific Food Board of the European Union accept a daily intake of10 mg p-carotene to be completely safe for all persons including smokers. Taking into account the eating habits in Germany the mean topical p-carotene intake per person is about 2 mg. At high intake of fruits and vegetables one can reach about 4 mg a day. p-Carotene enriched food such as ACE juices are safe also for smokers if consumed in usual amounts such as one glass a day. The label on...

Nonrespiratory Functions Of The Lung

Mucociliary Transport

Top is moved up and out of the airways. Diseases such as cystic fibrosis and chronic bronchitis can affect mucous secretion. Second, alveolar macrophages provide an additional mechanism for removing particles deposited deeper in the lungs, where the blood-gas barrier must be very thin for gas exchange. Macrophages originate in the bone marrow and circulate in the blood as monocytes before settling in the respiratory zone of the lungs, where the epithelium is not ciliated. They roam the airway surfaces by ameboid action and engulf foreign particles by phagocytosis. Most foreign substances are destroyed by lysozymes inside the macrophage. However, carbon and mineral particles may be stored in residual bodies in the macrophage, which then settles in the interstitium. The effects of mineral dusts are especially insidious, leading to a progressive destruction of lung tissue, and even lung cancer in the case of asbestosis. Normal macrophages that do not settle in the interstitium leave the...

Extraction Circuit Psepl Psep2

1) Purification of the feedstock The feed raw material is regarded as the product from which certain components must be removed during the extraction process. Examples being the production of decaffeinated coffee and of nicotine-free tobacco. Furthermore, it may be required to recover both the solids as well as certain extracted components. In addition, there are cases where the plant must be operated in two stages extracting one component from the feedstock, storing it temporarily and, after the extraction of second constituent, returning it to the bulk material. This procedure is adopted when a certain component A is to be selectively removed while retaining a component B in the feedstock which is more volatile than A. For example, in the high pressure extraction of tea, it is essential to remove the tea aroma from a batch fed into an extraction vessel in order to add this aroma to an already decaffeinated batch in another vessel. A similar situation exists in the case of tobacco,...

Optimization Of Liposomal Delivery

Mlv Liposome

They are not cleared rapidly by Kupffer cells in the liver, and yet extravasate and penetrate across tight barriers. BIVs penetrated barriers including the endothelial cell barrier in normal mice and the posterior blood retinal barrier in adult mouse eyes, and diffused throughout large tumors 3 and several layers of smooth muscle cells in pig arteries. We demonstrated efficacy for treatment of non-small-cell lung cancer 3 using BIV DOTAP Chol-p53 DNA-liposome complexes and not by using SUV DOTAP Chol-p53 DNA-liposome complexes. Therefore, morphology of the complexes is essential.

Weightrelated amenorrhoea

Which may further suppress gonadotropin secretion. This pathway is enhanced by cigarette smoking. Weight-related gonadotropin deficiency is more pronounced with LH than FSH 49 . This and the reduction in pulsatility of gonadotropin secretion may result in a 'multicystic' pattern in the ovary. This appearance is typical of normal puberty and is seen when there are several cysts (about 5-10 mm in diameter) together with a stroma of normal density.

Pediatric Asthma Case Study

A 14-year-old African-American female is brought to the pediatrician's office by her mother. She has just started running on her high school track team, but has been complaining to her mother that her running feels different this year. When she ran in middle school she could race longer distances without becoming winded. She now says her chest burns and she is running fewer miles before she has to stop to catch her breath. Her girlfriend told her she could hear her wheezing and she should go to the nurse. The school nurse confirmed her wheezing and notified her mother to come pick her up from school. There is no history of asthma in the family but her parents both smoke cigarettes. The school nurse advised that cigarettes could be contributing to the child's respiratory complaints. At the pediatrician's office her peak flow is 380 L min, which is within 5 of her predicted value for her height and weight. She does complain of coughing at night. Her lung sounds are now clear with no...

Low penetrancemodifier genes

Polymorphisms in the N-acetyltransferase (NAT2) gene are associated with an altered rate of metabolism of carcinogens, with wild-type alleles producing a rapid acetylator phenotype and homozygosity for combinations of variant alleles resulting in a slow phenotype. It has been shown that there is a statistically significant interaction between acetylator status among BRCA1 carriers and the number of packs of cigarettes they smoke per week, duration of time they had smoked, or age at which they started smoking. This suggests that BRCA1 carriers who smoke are at increased risk of breast cancer if they are slow acetylators (Ambrosone et al., 1996 Rebbeck et al., 1997 Ambrosone et al., 1998).

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