Tired of being "controlled" by smoking? Nicotine: a powerful neuro-stimulant

When you smoke your heart rate soars and your whole nervous system is stimulated into greater agitation. A cigarette gives you a two minute fix of dopamine (brain chemical that feels good) combined with 48 hours of an agitated nervous system. You keep going back for that good feeling to counteract the agitation.... only to increase the agitation. Cigarettes hold out a promise of relaxation that they NEVER deliver!

"It feels wonderful to be free of cigarettes after years of trying..."

In these Stop Smoking Sessions we use the most powerful techniques available to ensure you get the best chance to quit you will ever receive. We don't take a cookie-cutter approach that relies on one technique. Instead we use a whole range of techniques to create a unique treatment session for you.

These methods are individually proven in research studies to be the most effective ways to stop smoking and are broadly based on Cognitive Behavioural Therapy (CBT) and Clinical Hypnotherapy. Each technique on it’s own could be 100% effective for you—however as one can never tell exactly which approach will “click” with a client we use several techniques in a powerful combination.

Cognitive Behavioural Therapy (CBT)

Of all psychotherapies CBT has the strongest evidential backing and is now the treatment of choice under the NHS. CBT aims to change thoughts and behaviours to bring about positive changes.

Clinical Hypnotherapy

works by taking you into a state of heightened suggestibility where your critical mind takes a break and we can work directly and deeply with your imagination and subconscious to create new beliefs, patterns and habits. (Read more about hypnotherapy here.)

CBT & Hypnotherapy combined

Research studies where are applied together have shown that they are strongly complementary and their effectiveness is raised many times when used in combination.

Blood pressure and coronary heart disease

Clinical Trials Research Unit, Department of Medicine, University of Auckland, New Zealand. c.lawes@ctru.auckland.ac.nz

Overviews of randomized controlled trials and prospective observational studies provide the most reliable data on the association between blood pressure and coronary heart disease (CHD). The totality of evidence indicates a strong association between blood pressure and CHD, which is continuous down to levels of at least 115 mm Hg systolic. Overall, for those 60 to 69 years of age, a 10 mm Hg lower systolic blood pressure is associated with about one-fifth lower risk of a CHD event. The size and shape of this association is consistent across regions, for males and females, and for fatal events as well as nonfatal myocardial infarction. Trials comparing active treatment to placebo or no treatment have demonstrated that the benefits of blood pressure lowering with different classes of drugs (e.g., diuretics, beta-blockers, ACE inhibitors, calcium antagonists) are broadly similar, with approximately one-fifth reduction in CHD. ACE inhibitors achieve this with relatively modest blood pressure reductions, but the size of the reduction for calcium antagonists remains uncertain and appears somewhat less than expected from the blood pressure reduction. Trials confirm the expectation from cohort studies of benefits increasing with the amount of blood pressure lowering, and benefit accruing among those with average or even below average blood pressure. Observational data suggest that the proportional association is attenuated with age, but attenuation is less evident in trial data. However, in both cohort studies and clinical trials, CHD risk differences associated with a given blood pressure difference increase with age. The important points to emerge from this review are, first, that the relative benefits of blood pressure lowering for CHD prevention are likely to be consistent across a range of different populations. Second, there is likely to be considerable benefit with blood pressure lowering below "traditional" hypertension thresholds, especially in those with high absolute risk. Third, initiating and maintaining the maximum tolerated blood pressure reduction is a more important issue than choice of initial agent. Finally, and most importantly, the large majority of people have suboptimal blood pressure (e.g., systolic > 115 mm Hg) and so initiatives to lower blood pressure population-wide are an essential adjunct to targeted treatment programs.

Smoking and Periodontal Disease

Periodontology and Oral Immunology, University of Glasgow Dental Hospital and School, 378 Sauchiehall Street, Glasgow, G2 3JZ, Scotland, UK

Numerous investigations of the relationship between smoking and periodontal disease have been performed over the last 15 years, and there now exists a substantial body of literature upon which this current review is based. From both cross-sectional and longitudinal studies, there appears to be strong epidemiological evidence that smoking confers a considerably increased risk of periodontal disease. This evidence is further supported by the data emanating from patients who stop smoking. These patients have levels of risk similar to those of non-smokers. Numerous studies of the potential mechanisms whereby smoking tobacco may predispose to periodontal disease have been conducted, and it appears that smoking may affect the vasculature, the humoral immune system, and the cellular immune and inflammatory systems, and have effects throughout the cytokine and adhesion molecule network. The aim of this review is to consider the evidence for the association between smoking and periodontal diseases and to highlight the biological mechanisms whereby smoking may affect the periodontium.

Smoking and Haert Disease

Smoking and heart disease: PREVENTION IS THE CURECardiovascular disease is the most common cause of death in the developed countries. More than half of these deaths result directly from coronary artery disease. Another approximately 20 percent are due to stroke. With such a large amount of disease related to cardiovascular disease, it is imperative to look at the main reasons.The science of epidemiology (the scientific study of disease patterns and causes) has led to an understanding of the concept of the risk factors. A risk factor is a feature or tendency in a population or individual that is associated with an increased risk of developing future disease(s). Some risk factors can not be changed; these include heredity, gender, and age. In contrast, some risk factors are modifiable or changeable; smoking is one of these.Cigarette smoking remains the most changeable risk factor for coronary artery disease (CAD) in much of the world. Approximately, 1 billion individuals worldwide now; 5 million people die annually of causes (including heart disease) directly related to smoking. It is important to note that even nonsmokers who have passive exposure to cigarettes, cigars, or pipe smoke have an increased risk of CAD from this exposure.The effects of smoking for coronary risk have been absolutely proved over the past fifty years. People who consume 20 or more cigarettes daily have a two to three times increase of total CAD compared to nonsmokers. In young women whoTake the contraceptive pill and who smoke there is an even greater increase in CAD, because of the additive effects of these two entities. Smoking increases the disease of coronary arteries (arthrosclerosis). Consequently, there is a significant association between smoking and angina (chest pain because of narrowed coronary arteries), first-time heart attacks, as well as repeated heart attacks. Likewise, there is an increase in all forms of stoke associated with smoking.Smoking causes the blood pressure to rise. It also decreases the amount of oxygen that gets to the heart muscle. The chemicals in cigarette smoke, including nicotine and carbon monoxide (a deadly poison in high doses), accelerate the to blood vessels through arterial diseases. Apart from making the dangerous LDL cholesterol ( low density lipoprotein) more harmful and worsening arterial damage, smoking increases the tendency of blood to form clots.Another way in which smoking affects the heart is through the damage it causes to the lungs. As the lungs are altered by exposure to the smoke, a change takes place in the circulation of the lungs that is normally a very low pressure system. Lung damage causes the pressure in the blood vessels of the lung to rise. This results in a strain on the right ventricle (pumping chamber) of the heart-which is designed to function with low pressures-and can cause permanent damage to the heart.Another condition which is directly related to the smoking is Buerger’s disease. In this disease inflammation takes place in the small and medium- sized arteries and veins in the arms and legs. This occurs mostly in man under the age of 40 and more commonly in Asians and individuals of eastern European origin. The only specific treatment is for the patient to stop smoking.Smoking has very negative effects on health generally, and on the cardiovascular system specifically. Yet the tobacco industry continues to aggressively target all populations- especially young adults. It is therefore very important that preventing people from starting to smoke be the most important strategy. The message should also be clear that smoking cessation cuts the health risks; cutting down on smoking does not.PREVENTION IS NOT ONLY BETTER THAN CURE-IT IS THE CURE!

Pharmacology of Nicotine: Addiction, Smoking-Induced Disease

Neal L. Benowitz

Departments of Medicine and Biopharmaceutical Sciences, Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, University of California, San Francisco, California 94143-1220; email:

Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized by CYP 2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.

Cigarette Smoking and Incident Chronic Kidney Disease

Charlotte Jones-Burton^a, Stephen L. Seliger^{a, b}, Roberta W. Scherer^c, Shiraz I. Mishra^b, Ghazal Vessal^d, Jeanine Brown^a, Matthew R. Weir^a, Jeffrey C. Fink<sup>a, b

a</sup>Department of Medicine, University of Maryland School of Medicine, and
^bDepartment of Epidemiology and Preventive Medicine, University of Maryland School of Pharmacy, and
^cDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., USA;
^dFaculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease.

Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. miguel_hernan@post.harvard.edu

We conducted a systematic review to summarize the epidemiological evidence on the association between cigarette smoking, coffee drinking, and the risk of Parkinson's disease. Case-control and cohort studies that reported the relative risk of physician-confirmed Parkinson's disease by cigarette smoking or coffee drinking status were included. Study-specific log relative risks were weighted by the inverse of their variances to obtain a pooled relative risk and its 95% confidence interval (CI). Results for smoking were based on 44 case-control and 4 cohort studies, and for coffee 8 case-control and 5 cohort studies. Compared with never smokers, the relative risk of Parkinson's disease was 0.59 (95% CI, 0.54-0.63) for ever smokers, 0.80 (95% CI, 0.69-0.93) for past smokers, and 0.39 (95% CI, 0.32-0.47) for current smokers. The relative risk per 10 additional pack-years was 0.84 (95% CI, 0.81-0.88) in case-control studies and 0.78 (95% CI, 0.73-0.84) in cohort studies. Compared with non-coffee drinkers, relative risk of Parkinson's disease was 0.69 (95% CI, 0.59-0.80) for coffee drinkers. The relative risk per three additional cups of coffee per day was 0.75 (95% CI, 0.64-0.86) in case-control studies and 0.68 (95% CI, 0.46-1.00) in cohort studies. This meta-analysis shows that there is strong epidemiological evidence that smokers and coffee drinkers have a lower risk of Parkinson's disease. Further research is required on the biological mechanisms underlying this potentially protective effect.

Cigarette smoking and the incidence of Parkinson's disease in two prospective studies.

Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. miguel_hernan@post.harvard.edu

An inverse association between cigarette smoking and idiopathic Parkinson's disease has been reported in several retrospective studies, but prospective evidence is available only for men. We assessed the association between the incidence of Parkinson's disease and smoking in two large prospective cohort studies comprising men and women. New cases of Parkinson's disease were identified in the Nurses' Health Study for 1976-1996, and in the Health Professionals Follow-up Study for 1986-1996. Smoking history was assessed at baseline and updated on subsequent biennial questionnaires. In women, the age-adjusted rate ratios (95% confidence intervals) for Parkinson's disease relative to never-smokers were 0.7 (0.5, 1.0) for past smokers, and 0.4 (0.2, 0.7) for current smokers. In men, the age-adjusted rate ratios for Parkinson's disease relative to never-smokers were 0.5 (0.4, 0.7) for past smokers, and 0.3 (0.1, 0.8) for current smokers. In both cohorts, the strength of the association decreased with time since quitting (among past smokers), increased with number of cigarettes per day (among current smokers), and increased with pack-years of smoking. These prospective findings confirm that an inverse association between smoking and the incidence of Parkinson's disease exists in both men and women.

Risk and protective factors for Parkinson's disease: a study in Swedish twins.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-181 77 Stockholm, Sweden.

Many studies have shown a protective effect of cigarette smoking on Parkinson's disease. However, criticism has been raised concerning confounding by genetic factors. We investigated the associations between Parkinson's disease and smoking, alcohol, coffee, area of living, and education in a co-twin control study. Because twins are matched for genetic and familial environmental factors, this design controls for confounding by these factors. We also examined control subjects unrelated to cases. Exposure information was taken from questionnaires answered in the 1960s and 1970s. Parkinson's disease cases were identified through the Swedish Inpatient Discharge Register (IDR) and the Cause of Death Register. In the unrelated control subject comparison, 476 Parkinson's disease cases and 2,380 control subjects were included. In the co-twin control comparison, 415 same-sex twin pairs were included. There was an inverse association between smoking and Parkinson's disease using unrelated control subjects and co-twin control cases. There was no association between Parkinson's disease and alcohol, coffee, or area of living. High educational level was associated with Parkinson's disease in the unrelated control subject comparison but not in the co-twin control comparison. We confirm the protective effect of smoking on Parkinson's disease and establish that the association is only partially explained by genetic and familial environmental factors.

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese

Department of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg

INTRODUCTION: Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE: We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS: 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), p="0.019)," p="0.001)," p="0.006)." p="0.006)," p="0.014)," p="0.003)," p="0.044)," p="0.016)">

Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies.

Stockholm Gerontology Research Center, NEUROTEC, Karolinska Institute, Huddinge University Hospital, Sweden. laura.fratiglioni@neurotec.ki.se

The relationship between smoking and neurological diseases has always been controversial. Even the expected association between smoking and increased risk for cerebrovascular disease has been debated for years. It was at the end of the 1980s that smoking became definitively accepted as a risk factor for ischemic stroke. More recently, two other neurological diseases have been studied in relation to smoking: Parkinson's disease (PD) and Alzheimer's disease (AD). Many epidemiological studies have found a highly significant negative association between cigarette smoking and these two neurodegenerative disorders. The risk of AD or PD in nonsmokers has generally been about twice that of smokers. That is, patients with AD or PD are approximately 50% less likely to have smoked cigarettes during their lifetime than are age- and gender-matched controls. Alternatively, cigarette smokers are 50% less likely to have PD or AD than are age- and gender-matched nonsmokers. This statistically significant negative association has been interpreted as suggesting that cigarette smoking exerts an undefined, biologic, neuroprotective influence against the development of PD and AD. A review of all studies that either support or refute this hypothesis is presented separately for PD and AD.

Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue?

Department of Public Health Sciences, School of Public Health, University of Hawaii, Honolulu 96822, USA.

We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.

The "protective" influence of cigarette smoking on Alzheimer's and Parkinson's diseases. Quagmire or opportunity for neuroepidemiology?

Department of Neurology, West Virginia University School of Medicine, Morgantown, USA.

The negative association between smoking and both Alzheimer's (AD) and Parkinson's (PD) diseases is a consistent epidemiologic finding. This observation has prompted many investigators to conclude that cigarette smoking must be "biologically protective" against AD and PD. Rather than suggesting some as-yet-undefined pathogenetic clue, however, this negative association more likely is indicative of the under-appreciated influence of differential survival in epidemiologic studies.

Smoking and Parkinson's and Alzheimer's disease

Stockholm Gerontology Research Center, NEUROTEC, Karolinska Institute, Huddinge University Hospital, Sweden. laura.fratiglioni@neurotec.ki.se

The relationship between smoking and neurological diseases has always been controversial. Even the expected association between smoking and increased risk for cerebrovascular disease has been debated for years. It was at the end of the 1980s that smoking became definitively accepted as a risk factor for ischemic stroke. More recently, two other neurological diseases have been studied in relation to smoking: Parkinson's disease (PD) and Alzheimer's disease (AD). Many epidemiological studies have found a highly significant negative association between cigarette smoking and these two neurodegenerative disorders. The risk of AD or PD in nonsmokers has generally been about twice that of smokers. That is, patients with AD or PD are approximately 50% less likely to have smoked cigarettes during their lifetime than are age- and gender-matched controls. Alternatively, cigarette smokers are 50% less likely to have PD or AD than are age- and gender-matched nonsmokers. This statistically significant negative association has been interpreted as suggesting that cigarette smoking exerts an undefined, biologic, neuroprotective influence against the development of PD and AD. A review of all studies that either support or refute this hypothesis is presented separately for PD and AD.

Alcohol-related illness in teens is up 15 per cent in wake of 24-hour drinking

The number of teenagers receiving medical treatment after drinking binges has risen by nearly 15 per cent in the year the new 24-hour licensing laws were introduced.

The shock increase, recorded just months after the law changed, means hundreds more under-18s have suffered liver disease, blood poisoning and mental disorders - including depression and psychosis - as a result of alcohol.

It delivers a crushing blow to Labour's flagship legislation, which Ministers promised would bring about a revolution in the UK's drinking culture.

• Special report: Binge drinking Britain

Culture Minister Tessa Jowell insisted that longer opening hours would put an end to hurried bingeing and the violence at closing time when drinkers were all turfed out on to the streets simultaneously.

But the new figures - released by the Government in answer to a question in Parliament - give the lie to claims that staggered closing times would encourage a healthier, 'cafe culture' attitude.

From April 2005 to April 2006, teenagers were admitted to hospital for treatment 8,582 times, an increase of nearly 1,000 more than in the previous year. The figure, the first published following the introduction of the new laws in November 2005, is the biggest rise in a decade.

Doctors, horrified by the sudden increase, say it can only be explained by the longer opening hours.

Dr Christopher Record, consultant in liver disease at Newcastle NHS Trust, blames the constant availability of alcohol.

He said: 'There is no doubt that increased availability has led to more young people drinking. If you increase availability you increase consumption. The two go hand in hand.

'I'm sure the rise has been caused by 24-hour drinking legislation, when you can go into Asda and buy alcohol throughout the night.'

Dr Record was part of the Government consultation ahead of the new legislation. But he claims his pleas and those of other doctors who treat the results of binge drinking were ignored.

'The licensing laws were changed without any reference to what was happening in society,' he said.

'The Government wanted to introduce this Mediterranean cafe culture and it was complete pie in the sky.

'We are now drinking 50 per cent more alcohol than we did 30 years ago. But the Government doesn't take any notice. The alcohol lobby has tremendous influence.'

Sir Michael Marmot, a professor studying the effects of alcohol on society, said: 'This is a very worrying trend. UK teenagers are among the heaviest drinkers in Europe. The whole idea of encouraging a sensible drinking culture in this country simply isn't working.'

Studies by NHS statisticians at the Information Centre for Health and Social Care has shown that underage drinkers are more likely to buy alcohol to drink in secret than try to get served in a pub.

Yet more than half of the 3,000 extra-hours permits issued under the relaxed laws were given to corner shops, supermarkets and off-licences.

Campaigner Frank Soodeen, of charity Alcohol Concern, said: 'We have been monitoring hospital admissions due to drink among young people for some time and we have been concerned by the rising trend. But this figure is shocking.'

However, a spokeswoman for the Department for Culture, Media and Sport said: 'It is against the law to sell alcohol to under-18s and we have put in force much tougher penalties.

'You can now be fined up to £5,000 for selling to underage drinkers and the police and local authorities are not shy in using their powers.'

UK's binge drinking culture may make liver disease a big killer

Liver disease could become one of the biggest killers in the UK as a result of the country’s binge drinking culture, according to a new study.

The survey, commissioned by the London Clinic in Harley Street, shows that half of Britain’s young adults first got drunk before the age of 15.

It found that 48 per cent of those in the 18 to 24 age group were between the ages of 13 and 15 when they first got drunk, while 6 per cent were aged under 12.

The survey, of 1,038 people, also revealed that 14 per cent of men and 11 per cent of women drink every day and 6 per cent of men drink more than a week’s recommended alcohol intake in one night.

Deaths from cirrhosis of the liver caused by alcohol abuse have doubled in the past 10 years and the condition in young people has increased eight-fold.

Cirrhosis is killing more women than cervical cancer and more men than Parkinson’s disease.

“Particularly worrying is the early age at which young people are starting to
drink,” the Independent quoted Professor Roger Williams, director of the London Clinic Liver Centre, as saying.

His colleague, Professor Max Malago, a liver surgeon, added: “If current trends continue, Britain faces an epidemic of liver disease that threatens to eclipse that of diseases like breast cancer. Binge-drinking is a key culprit but it’s not the only one. Diet is also partly to blame.”

The survey also highlighted what it describes is “an ignorance” of liver disease among drinkers.

It says 71 per cent of men and 78 per cent of women think that regular drinking only presents a low risk of liver disease.

Chip Tech Aids Eye Disease Diagnosis Over Net

Ophthalmologist Edward Chaum of the University of Tennessee came up with the idea after a visit to the Oak Ridge National Laboratory in Tennessee. Chaum learned that engineers at the facility used an image recognition system to virtually automate the process of identifying bad chips, by comparing chip images to a database filled with bad batch examples.

"As [the engineer] was describing his methodology to me, it became very clear that what he was doing was exactly what I do as a physician when I'm examining a patient with diabetic retinopathy," Chaum said in regards to his visit. I look for specific features that are present in that retina and I go into my own [mental] library — thousands and thousands of patients I've seen over the years — to say, 'This is diabetic retinopathy of a certain level'" he continued.

"Telemedicine" has been a new field which doctors have only just begun to explore, but already it is opening the doors for new avenues of health care that some communities literally have no access to. Currently Chaum still goes over the results of his image recognition system to verify accuracy, however he has gone on record to state that it may only be a matter of months before the entire process is automated.

Pediatric Eye Disease Investigator Group Amblyopia Treatment

Correspondence: Requests for reprints should be addressed to: Megan G. Rees, M.D., 803–805 W. Broadway, Vancouver, BC, Canada V5Z 1K1.

Introduction: The Pediatric Eye Disease Investigator Group (PEDIG), formed in 1997, has been dedicated to clinical research of eye diseases affecting children. Over the last three years, PEDIG has studied the efficacy of amblyopia treatment regimes, and has followed the long-term outcomes of these regimes. These studies are known as the Amblyopia Treatment Studies (ATS) and have been sorted into eight categories. Four of these have been published and four are still awaiting publication.

Method: A survey of ophthalmologists and orthoptists attending a seminar in British Columbia, Canada. They were questioned as to how they treat amblyopia in light of the PEDIG studies.

Results: Ninety percent continue to use patching as their first method of treatment in moderate amblyopia. Over 50% will patch four hours/day or more to begin treatment and 83% will use near exercises to augment the patching. Two thirds will begin patching six or more hours/day in patients with severe amblyopia. Those that use atropine, use it daily rather than on weekends. Most felt that amblyopia could be treated to age 12 years and some thought it could be treated to 14 years.

Conclusion: Most ophthalmologists and orthoptists taking the survey have not significantly changed their approach to amblyopia treatment in light of the recent PEDIG studies.

Tamoxifen-associated eye disease.

Chemoprevention Branch, National Cancer Institute, Bethesda, MD, 20892, USA. PURPOSE: The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease. Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed. DESIGN: National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed. RESULTS: Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities. Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen. Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms. CONCLUSION: Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use. Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints.

The Aging Eye: Preventing and Treating Eye Disease

Four common eye diseases pose the greatest threats to vision after age 40: cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy. This report will help you determine your risk of developing these disorders, describe their symptoms, and discuss diagnosis and treatment. You'll also learn to recognize and address other common eye problems, including presbyopia, dry eye, floaters and flashes, retinal detachment, and eyelid problems such as drooping upper or lower lids.

Prepared by the editors of Harvard Health Publications in consultation with Laura C. Fine, M.D., Clinical Instructor in Ophthalmology, Harvard Medical School, and Jeffrey S. Heier, M.D., Clinical Instructor in Ophthalmology, Harvard Medical School. 48 pages. (2007)

Diagnosis and Treatment of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries.
Aim: To provide a comprehensive, updated review of diagnosis and management of NAFLD and to appraise the evolution of new modalities in these areas.
Methods: An Ovid MEDLINE search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated.
Results: The diagnosis of hepatic steatosis and steatohepatitis or non-alcoholic steatohepatitis (NASH) is not yet possible without liver biopsy. This is impractical given the large numbers affected by the condition. Current therapy has focused on improving insulin resistance and mediators of inflammation, factors probably associated with disease progression.
Conclusions: There are no proven non-invasive diagnostic modalities to distinguish NAFLD and NASH, but new biomarker panels are approximating the liver biopsy in accuracy. Therapeutic targets of drug development are in early stages, but a multifaceted approach will probably yield several treatment options in the years to come.

Introduction

Fatty liver disease is not a new condition, and indeed, alcohol-induced liver injury dates back thousands of years. The entity of non-alcoholic fatty liver disease (NAFLD) is also not a new condition, but was not appreciated in early reports. In the 1950s, livers consistent with non-alcoholic steatohepatitis (NASH) were described in obese individuals, but surreptitious alcohol use was suspected.^[1] In the now famous report of Ludwig et al. in 1980, the term NASH was coined.^[2] It was not until the 1990s, however, that the prevalence and increasing incidence of the condition brought it into the limelight. It was not coincidence that the recognition of NAFLD paralleled the alarming increase in body mass index (BMI) in the American population^[3] (Figure 1). The umbrella term of NAFLD embodies simple steatosis, NASH and advanced fibrosis or cirrhosis related to this pathological entity.

Guidelines for the diagnosis and treatment of alcoholic liver disease

Min De ZENG*, You Ming LI ^† , Cheng Wei CHEN ^‡ , Lun Gen LU*, Jian Gao FAN ^§ , Bing Yuan WANG ^¶ & Yi Min MAO*

*Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ^† Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ^‡ Clinical Center for Hepatology, No. 85 Army Hospital, Shanghai, ^§ Department of Gastroenterology, Shanghai First People's Hospital, Jiaotong University, Shanghai, ^¶ Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, China

Correspondence to: Min De ZENG, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai 200001, Shanghai Jiaotong University School of Medicine, Shanghai, China. Email:

Alcoholic Liver Disease

Alcoholic liver disease usually occurs after years of excessive drinking. The longer the alcohol use and the more alcohol that was consumed, the greater the likelihood of developing liver disease.

Acute alcoholic hepatitis can result from binge drinking. It may be life-threatening if severe.

People who drink excessively can become malnourished because of the empty calories from alcohol, reduced appetite, and poor absorption of nutrients in the intestines. Malnutrition contributes to liver disease.

Other factors that contribute to the development of alcoholic liver disease:

• Genetic factors
• Personal susceptibility to alcohol-induced liver disease
• Toxicity of alcohol (ethanol) to the liver

Alcoholic liver disease does not affect all heavy drinkers. Women may be more susceptible than men. It is not necessary to get drunk for the disease to develop.

Problem Drinking and Alcoholism: Diagnosis and Treatment

MARY-ANNE ENOCH, M.D., M.R.C.G.P., and DAVID GOLDMAN, M.D.
National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland

Alcoholism is one of the most common psychiatric disorders with a prevalence of 8 to 14 percent. This heritable disease is frequently accompanied by other substance abuse disorders (particularly nicotine), anxiety and mood disorders, and antisocial personality disorder. Although associated with considerable morbidity and mortality, alcoholism often goes unrecognized in a clinical or primary health care setting. Several brief screening instruments are available to quickly identify problem drinking, often a pre-alcoholism condition. Problem drinking can be successfully treated with brief intervention by primary care physicians. Alcohol addiction is a lifelong disease with a relapsing, remitting course. Because of the potentially serious implications of the diagnosis, assessment for alcoholism should be detailed. Alcoholism is treated by a variety of psychosocial methods with or without newly developed pharmacotherapies that improve relapse rates. Screening for problem drinking and alcoholism needs to become an integral part of the routine health screening questionnaire for adolescents and all adults, particularly women of child-bearing age, because of the risk of fetal alcohol syndrome. (Am Fam Physician 2002;65:441-8,449-50. Copyright© 2002 American Academy of Family Physicians.)

Alcohol misuse is associated with considerable morbidity and mortality (100,000 deaths annually), social and legal problems, acts of violence, and accidents. Alcoholism is among the most common psychiatric disorders in the general population: the lifetime prevalence of alcohol dependence, the severe form of alcoholism, is 8 to 14 percent.¹ The ratio of alcohol dependence to alcohol abuse is approximately two to one. The incidence of alcoholism is still more common in men, but it has been increasing in women, and the female to male ratio for alcohol dependence has narrowed to one to two.² Serious drinking often starts in adolescence; approximately 40 percent of alcoholics develop their first symptoms between 15 and 19 years of age.³

Alcoholism often goes undiagnosed; the rate of screening for alcohol consumption in health care settings remains lower than 50 percent.⁴ Some patients also may withhold information because of shame or fear of stigmatization. This can lead to missed information about medical and psychiatric conditions, potential surgical complications, unexpected alcohol withdrawal symptoms, drug interactions, and lost opportunities for prevention, including intervention during pregnancy to prevent damaging effects of alcohol on the fetus. All too often, patients, particularly the elderly, continue to be treated symptomatically for alcohol-related conditions without recognition of the underlying problem (Table 1). There are many reasons why there is a worldwide tendency for physicians to neglect or be unaware of symptoms and signs of alcohol abuse, but inappropriate attitudes, insufficient medical school training in this subject, and subsequent low confidence to treat are key elements.

How Can I Get an Alcoholic Into Treatment?

If an alcoholic is unwilling to seek help, is there any way to get him or her into treatment?

This can be a challenging situation. An alcoholic cannot be forced to get help except under certain circumstances, such as when a violent incident results in police being called or following a medical emergency.

This doesn't mean, however, that you have to wait for a crisis to make an impact. Based on clinical experience, many alcoholism treatment specialists recommend the following steps to help an alcoholic accept treatment:

Stop all "rescue missions." Family members often try to protect an alcoholic from the results of his or her behavior by making excuses to others about his or her drinking and by getting him or her out of alcohol-related jams. It is important to stop all such rescue attempts immediately, so that the alcoholic will fully experience the harmful effects of his or her drinking -- and thereby become more motivated to stop.

Time your intervention. Plan to talk with the drinker shortly after an alcohol-related problem has occurred--for example, a serious family argument in which drinking played a part or an alcohol-related accident. Also choose a time when he or she is sober, when both of you are in a calm frame of mind, and when you can speak privately.

Be specific. Tell the family member that you are concerned about his or her drinking and want to be supportive in getting help. Back up your concern with examples of the ways in which his or her drinking has caused problems for both of you, including the most recent incident.

State the consequences. Tell the family member that until he or she gets help, you will carry out consequences--not to punish the drinker, but to protect yourself from the harmful effects of the drinking. These may range from refusing to go with the person to any alcohol-related social activities to moving out of the house. Do not make any threats you are not prepared to carry out.

Be ready to help. Gather information in advance about local treatment options. If the person is willing to seek help, call immediately for an appointment with a treatment program counselor. Offer to go with the family member on the first visit to a treatment program and/or AA meeting.

Call on a friend. If the family member still refuses to get help, ask a friend to talk with him or her, using the steps described above. A friend who is a recovering alcoholic may be particularly persuasive, but any caring, nonjudgmental friend may be able to make a difference. The intervention of more than one person, more than one time, is often necessary to persuade an alcoholic person to seek help.

Find strength in numbers. With the help of a professional therapist, some families join with other relatives and friends to confront an alcoholic as a group. While this approach may be effective, it should only be attempted under the guidance of a therapist who is experienced in this kind of group intervention.

Get support. Whether or not the alcoholic family member seeks help, you may benefit from the encouragement and support of other people in your situation. Support groups offered in most communities include Al-Anon, which holds regular meetings for spouses and other significant adults in an alcoholic's life, and Alateen, for children of alcoholics. These groups help family members understand that they are not responsible for an alcoholic's drinking and that they need to take steps to take care of themselves, regardless of whether the alcoholic family member chooses to get help.

Antioxidant supplements for non-alcoholic fatty liver disease and/or steatohepatitis

No evidence to support or refute antioxidant supplements for patients with non-alcoholic fatty liver disease and/or steatohepatitis

Non-alcoholic fatty liver disease is characterised by fatty deposition in the hepatocytes in the absence of excessive alcohol intake and of other known causes of fatty liver. Hepatic injury might be improved by antioxidant supplements. This systematic review identified six randomised clinical trials. No liver-related or unrelated deaths occurred in any of the included trials. Adverse events were minor and non-specific. Treatment with antioxidant supplements showed a significant, though not clinically relevant, amelioration of aspartate aminotransferase, but not of alanine aminotransferase, as compared to placebo or other interventions. Data on the radiological and/or histological response were too limited to draw any conclusions. Further placebo-controlled trials are necessary.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2009 Issue 1, Copyright © 2009 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Lirussi F, Azzalini L, Orando S, Orlando R, Angelico F. Antioxidant supplements for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD004996. DOI: 10.1002/14651858.CD004996.pub3.

This version first published online: January 24. 2007

Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is characterised by fatty deposition in the hepatocytes of patients with minimal or no alcohol intake and without other known cause. NAFLD includes a wide spectrum of histologic abnormalities ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), or even cirrhosis. Antioxidant supplements, therefore, could potentially protect cellular structures against oxidative stress and the resulting lipid peroxidation.

Objectives

To systematically evaluate the beneficial and harmful effects of antioxidant supplements versus no intervention, placebo, or other interventions for patients with NAFLD or NASH.

Search strategy

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2006), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), and The Chinese Biomedical Database (1978 to June 2006). No language restrictions were applied.

Selection criteria

Randomised clinical trials evaluating any antioxidant supplements versus no intervention, placebo, or other interventions in patients with NAFLD or NASH. Our inclusion criteria for NAFLD or NASH were based on history of minimal or no alcohol intake, imaging techniques showing hepatic steatosis, and/or histological evidence of hepatic damage (including simple steatosis, fatty infiltration plus nonspecific inflammation, steatohepatitis, fibrosis, and cirrhosis), and by exclusion of other causes of hepatic steatosis.

Data collection and analysis

We extracted data from the identified trials and contacted authors. We used a random-effects model and fixed-effect model with the significant level set at P = 0.05. We evaluated the methodological quality of the randomised trials by looking at how the generation of allocation sequence, allocation concealment, blinding, and follow-up were performed. We made our analyses following the intention-to-treat method by imputing missing data.

Main results

We identified six trials: two were regarded of high methodological quality and four of low methodological quality. None of the trials reported any deaths. Treatment with antioxidant supplements showed a significant, though not clinically relevant, amelioration of aspartate aminotransferase levels, but not of alanine aminotransferase levels, as compared to placebo or other interventions. Gamma-glutamyl-transpeptidase was decreased, albeit not significantly, in the treatment arm. Radiological and histological data were too limited to draw any definite conclusions on the effectiveness of these agents. Adverse events were non-specific and of no major clinical relevance.

Authors' conclusions

There is insufficient data to either support or refute the use of antioxidant supplements for patients with NAFLD. It may be advisable to carry out large prospective randomised clinical trials on this topic.

Treatment of alcoholic liver disease

INTRODUCTION — There are at present few specific therapies available for patients with alcoholic liver disease. There is, however, one extremely important intervention — abstinence — since continued alcohol ingestion is the single most important risk factor for progression in patients with alcoholic liver disease. Abstinence is also critical for those patients with advanced disease who may eventually require liver transplantation; in this setting, continued drinking will remove the patient from consideration. Referral to a rehabilitation program is usually necessary in combination with family support and counseling.

PREVENTION — Abstinence is the most effective means to prevent alcohol-related liver injury. In addition, several drugs have been studied to improve rates of abstinence but none is used routinely.

Abstinence — Abstinence can be beneficial even in patients with advanced histologic and clinical features. Improvement in fibrosis, a reduction in or even normalization of the portal pressure , and resolution (or easier treatment) of ascites have accompanied alcohol abstinence in some patients.

Disulfuram — Disulfuram, approved by the FDA in 1983, inhibits the activity of ALDH and, after alcohol ingestion, results in plasma acetaldehyde levels 5 to 10 times that seen in the absence of disulfuram. The accumulation of acetaldehyde leads to facial flushing, tachycardia, hypotension, dyspnea, nausea, vomiting, headache, blurred vision, vertigo, and anxiety within 15 to 30 minutes of alcohol ingestion. The syndrome lasts for several hours and the inhibitory activity lasts for several days. Due to its poor tolerability and "black box" warning regarding use in patients who are actively drinking, there is little evidence showing that disulfuram encourages abstinence.

Naltrexone — Naltrexone, a pure opioid antagonist, approved in 1995 for the treatment of alcoholism, controls the craving for alcohol. However, it also has a black box warning related to its potential for hepatocellular injury. In a review of 29 randomized controlled trials of naltrexone and nalmefene (another opioid antagonist), short-term treatment with naltrexone lowered the risk of relapse of alcohol abuse.

Alcoholic Liver Disease

Alcohol causes a spectrum of liver injury that can progress from fatty liver to alcoholic hepatitis (often considered an intermediate stage) to cirrhosis.

Alcohol consumption is high in most Western countries. In the US, annual ingestion is estimated at 10 L of pure ethanol equivalent per person; 15 million people abuse or are dependent on alcohol. The male:female ratio is 11:4.

Risk Factors

The major causative factors in alcoholic liver disease are quantity of alcohol consumed, duration of alcohol abuse (usually > 8 yr), nutritional status, and genetic and metabolic traits. Among susceptible people, a linear correlation generally exists between the amount and duration of alcohol use and the development of liver disease. As little as 20 g of alcohol in women or 60 g in men can cause serious liver damage when consumed daily for several years. Consuming more than 60 g/day for 2 to 4 wk produces fatty liver even in otherwise healthy men; 80 g/day may lead to alcoholic hepatitis; and 160 g/day over a decade can lead to cirrhosis. Alcohol content is estimated to be the beverage volume (in mL) multiplied by its percentage of alcohol. For example, 16 mL of alcohol is contained in roughly 40 mL of an 80‑proof (40% alcohol) beverage. Each mL of alcohol contains about 0.79 g. Although values can vary, the percentage of alcohol is about 2 to 7% for most beers and 10 to 15% for most wines.

Only 10 to 20% of alcoholics develop cirrhosis. Women are more susceptible than men (even when adjusting for smaller body size), probably because women have less alcohol dehydrogenase in their gastric mucosa, which lessens the first-pass oxidation of alcohol. Alcoholic liver disease often runs in families, suggesting genetic factors (eg, deficiency of cytoplasmic enzymes that eliminate alcohol). Malnutrition, particularly protein-energy malnutrition, increases susceptibility. Other risk factors include a diet high in unsaturated fat, iron deposition in the liver, and concomitant hepatitis C virus infection.

Pathophysiology

Alcohol is readily absorbed from the stomach and small intestine. It cannot be stored; > 90% is metabolized through oxidation. The first breakdown product is acetaldehyde, which is produced by three enzymatic pathways: alcohol dehydrogenase (responsible for about 80% of metabolism), cytochrome P‑450 2E1 (CYP2E1), and catalase.

Acetaldehyde is converted to acetate by mitochondrial aldehyde dehydrogenase. Chronic alcohol consumption enhances acetate formation. The processes generate hydrogen, which converts nicotinamide-adenine dinucleotide (NAD) to its reduced form (NADH), increasing the redox potential in the liver. This replaces fatty acids as a fuel, lowers fatty acid oxidation, and allows triglycerides to accumulate, causing fatty liver and hyperlipidemia. The excess hydrogen also converts pyruvate to lactate, which decreases glucose production (hypoglycemia can result), causing renal acidosis, reduced urate excretion, hyperuricemia, and thus gout.

Alcohol metabolism may also make the liver hypermetabolic, causing hypoxia and free radical–induced lipid peroxidative damage. Alcohol and undernutrition deplete antioxidants, such as glutathione and vitamins A and E, which predispose to such damage.

Acetaldehyde initiates much of the inflammation and fibrosis of alcoholic hepatitis. It transforms the stellate (Ito) cells lining liver blood channels (sinusoids) into fibroblasts that develop myocontractile elements and actively produce collagen. The sinusoids narrow and fill, limiting transport and blood flow. Gut endotoxins, which the impaired liver can no longer detoxify, lead to production of inflammatory cytokines. Acetaldehyde and lipid peroxidation products recruit leukocytes, resulting in production of more inflammatory cytokines. This elicits a vicious circle of inflammation that culminates in fibrosis and loss of hepatocytes.

Diagnosis and Treatment of Non-alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries.
Aim: To provide a comprehensive, updated review of diagnosis and management of NAFLD and to appraise the evolution of new modalities in these areas.
Methods: An Ovid MEDLINE search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated.
Results: The diagnosis of hepatic steatosis and steatohepatitis or non-alcoholic steatohepatitis (NASH) is not yet possible without liver biopsy. This is impractical given the large numbers affected by the condition. Current therapy has focused on improving insulin resistance and mediators of inflammation, factors probably associated with disease progression.
Conclusions: There are no proven non-invasive diagnostic modalities to distinguish NAFLD and NASH, but new biomarker panels are approximating the liver biopsy in accuracy. Therapeutic targets of drug development are in early stages, but a multifaceted approach will probably yield several treatment options in the years to come.

Introduction

Fatty liver disease is not a new condition, and indeed, alcohol-induced liver injury dates back thousands of years. The entity of non-alcoholic fatty liver disease (NAFLD) is also not a new condition, but was not appreciated in early reports. In the 1950s, livers consistent with non-alcoholic steatohepatitis (NASH) were described in obese individuals, but surreptitious alcohol use was suspected.^[1] In the now famous report of Ludwig et al. in 1980, the term NASH was coined.^[2] It was not until the 1990s, however, that the prevalence and increasing incidence of the condition brought it into the limelight. It was not coincidence that the recognition of NAFLD paralleled the alarming increase in body mass index (BMI) in the American population^[3] (Figure 1). The umbrella term of NAFLD embodies simple steatosis, NASH and advanced fibrosis or cirrhosis related to this pathological entity.

Avastin Shows Encouraging Results For Brain Cancer Treatment

Results of Avastin phase II trial from Genentech slow down aggressive brain cancer in phase II study and could possibly provide brain cancer treatment.

Genentech today announced that both study arms of a randomized, multi-center Phase II clinical study of Avastin (bevacizumab) administered alone or in combination with irinotecan chemotherapy demonstrated encouraging six-month progression-free survival (PFS) and objective response rate in patients with relapsed glioblastoma multiforme (GBM), the most common and aggressive type of brain cancer.

Assessed by independent radiological review, 36 percent (31/85) of GBM patients treated with Avastin alone, and 51 percent (42/82) of patients treated with Avastin in combination with chemotherapy, lived without the disease advancing within six months. No new or unexpected safety events related to Avastin have been observed in the study. The data were presented at the 12th Annual Scientific Meeting of the Society for Neuro-Oncology.

"Historical estimates suggest that only 15 percent of patients with this aggressive type of brain cancer live without their cancer progressing within six months," said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles and lead investigator for the study. "The findings suggested that at six months, more patients had lived without their cancer advancing when Avastin was administered as a single-agent or in combination with chemotherapy, than what we would normally expect."

"These findings exceeded our expectations, and due to the high unmet medical need of patients with relapsed GBM we plan to discuss these data with the FDA to determine next steps," said Hal Barron, M.D., Genentech's senior vice president, Development and chief medical officer.

According to the American Cancer Society (ACS), the five-year survival rate for patients with GBM is 3 percent, and has not changed in more than 25 years. The ACS estimates there will be 20,500 new cases of brain cancer and 12,740 brain cancer deaths in 2007.

Report of the Brain Tumor Progress

INTRODUCTION

Brain tumors represent a unique challenge in that they affect the organ that is the essence of the "self." Furthermore, because each area of the brain serves a different but vital function, the therapy that is most effective for other cancers--surgical removal of either the entire organ or the tumor with a generous surround of normal tissue--cannot be used to cure brain tumors. Unfortunately, most brain tumors are relatively insensitive to other cancer treatment, including radiation and chemotherapy.

Coupled with the difficulty in treating brain tumors is the unique biology of the brain:

• Brain tumors occur in an organ that is enclosed in a bony canal that allows little room for growth of the tumor without compressing and damaging normal brain.

• Many brain tumors extensively invade normally functioning brain, making complete surgical removal impossible.

• In their early stages, brain tumors are protected behind a blood-brain barrier; even when this barrier is disrupted in the bulk of the tumor, infiltrating tumor cells at the growing edge remain protected.

• Disruption of the blood-brain barrier leads to edema, which the brain tolerates poorly because of the limited intracranial space and the lack of lymphatics to rid itself of the products of edema and other debris.

• The brain itself is rich in expressed genes and therefore is a fertile field for the growth of both primary tumors and metastases.

• The brain and brain tumors appear to be less susceptible to attack by the immune system than are tumors in other organs. Even the term brain tumor, which suggests a single type of tumor, can be misleading. There are a bewildering variety of central nervous system tumors; the World Health Organization lists 126. Many of these tumors are not, strictly speaking, in the brain but arise from structures intimately associated with that organ, such as tumors of the covering membranes (meningiomas) and adjacent cranial and paraspinal nerves (schwannomas). Brain tumors range from benign (most meningiomas) to highly aggressive (glioblastomas). They affect both adults and children (although the distribution of tumors varies) and are often highly resistant to treatment.

The term brain cancer is also misleading. Most cancers that arise elsewhere in the body cause damage by metastasizing to other organs (including the brain). Primary brain tumors, however, rarely metastasize, although they may widely infiltrate the nervous system. Conversely, many cancers metastasize to the brain, making metastatic brain tumors much more common than primary brain tumors.

Throughout this document, the term brain tumor is used to refer to all tumors that grow inside the skull. The issues discussed in this document, however, also extend to tumors growing within the spinal canal.

Brain Tumor: Causes, Symptoms, Diagnosis And Treatment

The growth of abnormal cells in the tissues of the brain. Brain tumors can be benign (non-cancerous) or malignant (cancerous).

Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign or malignant tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges (membranes around the brain), nerves, or glands.

Causes of Brain Tumor

The cause of primary brain tumors is unknown. This is because they are rare, there are many types, and there are many possible risk factors that could play a role. Exposure to some types of radiation, head injuries, and hormone replacement therapy may be risk factors, as well as many others. The risk of using cell phones is hotly debated.

Genetic mutations and deletions of tumor suppressor genes (i.e., genes that suppress the development of malignant cells) increase the risk for some types of brain cancer. Inherited diseases that are associated with brain tumors include the following:

• Multiple endocrine neoplasia type 1 (pituitary adenoma)

• Neurofibromatosis type 2 (brain and spinal cord tumors)

• Retinoblastoma (malignant retinal glioma)

• Tuberous sclerosis (primary brain tumors)

• Von Hippel-Lindau disease (retinal tumor, CNS tumors)

Signs and Symptoms of Brain Tumor

Signs and symptoms can include the following:

• New onset or change in pattern of headaches

• Headaches that gradually become more frequent and more severe

• Unexplained nausea or vomiting

• Vision problems, such as blurred vision, double vision or loss of peripheral vision

• Gradual loss of sensation or movement in an arm or a leg

• Difficulty with balance

• Speech difficulties

• Confusion in everyday matter.

Diagnosis

Computed tomography (CT Scan): A computerized x-ray machine is used to take a series of detailed pictures from many different angles. Dye may be injected to help to clarify organs and tissues.

Magnetic Resonance Imaging (MRI): Powerful magnets waves are used to make a series of detailed pictures. Patients are injected with a substance called gadolinium to highlight possible cancer cells.

Angiogram. This imaging test uses a dye to visualize all the blood vessels in the brain to detect certain types of tumors.

Lumbar puncture/spinal tap. For this procedure, a special needle is placed into the lower back and into the spinal canal around the spinal cord. A small amount of cerebrospinal fluid, which surrounds the brain and spinal cord, can be removed and sent for testing.

Treatment

Surgery is required to determine whether a brain tumor exists and what type of tumor it is. A small sample of tumor tissue may be surgically removed and examined under a microscope. This is called a biopsy. Sometimes a biopsy is done by making a small hole in the skull and using a needle to extract a sample of the tumor.

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Mesothelioma Pain management

In general people think of treatment option in terms of eliminating the cancer from the patient's body. While doctors and patients often focus on treating the cancer, in many mesothelioma cases, the treatment of pain becomes the focus, either when little hope exists for effective treatment of the cancer, or when the treatment for the cancer causes a great deal of pain itself. For this reason, several treatment options exist to deal with a patient's pain management.

Once the doctor has assessed the pain, the doctor develops a treatment plan and discusses it with the patient. Medicines (also called drug therapy) are the main way to treat cancer pain. They include the use of opioids (or narcotics, the strongest pain relievers available), non-opioids (pain relieving medicines that are not opioids, such as acetaminophen and non-steroidal anti-inflammatory drugs, or NSAIDs), and adjuvant analgesics (medicines for purposes other than treatment of pain but that help in relieving pain in some situations). Other therapies such as relaxation techniques or biofeedback, physical therapy, anesthesia procedures, and surgical procedures can also help in treating some patients' cancer pain.

Non-opioids include medicines such as acetaminophen (also called Tylenol®), and NSAIDs such as ibuprofen. These medicines, the first choice for mild pain, relieve bone pain, superficial pain, muscle pain, and some other types of pain. In treating cancer pain, doctors often recommend the maximum daily dose. Anything greater than the maximum daily dose can cause significant side effects such as organ damage. Side effects vary, but in general NSAIDs use can result in gastrointestinal toxicity, with the most serious effects being ulcers and bleeding. NSAIDs also slow blood clotting, so they must be used cautiously in patients with bleeding or clotting disorders.
Opioids, the strongest pain relieving medicines including codeine, oxycodone, morphine, fentanyl, and hydromorphone, are excellent medicines for the treatment of cancer pain.
Opioids are sometimes classified as weak or strong depending on their effectiveness in relieving pain. Opioids such as morphine, hydromorphone, oxycodone, fentanyl, methadone, and levorphanol may have side effects that can limit the dose of the drug a patientc can receive. As a result, with any opioid managing the side effects is critical in effective pain control. These medicines can be given in a variety of ways, including orally and intervenously.

Adjuvant analgesics are medicines that have a purpose other than treatment of pain but that help relieve pain in some situations. A variety of adjuvant analgesics used to help relieve cancer pain exist. Doctors have found that some antidepressants relieve neuropathic pain as well as decrease depression. Anticonvulsants, generally used for seizure disorders, are useful in relieving tingling and burning pain, such as neuropathic pain. Doctors may use steroids relieve pain associated with swelling and with bone pain. Finally, local anesthetics can be put on the skin, injected into the spinal canal, and in some cases, be taken orally, and are useful for relieving tingling, burning-type pain.

Pneumonectomy

A pneumonectomy is the surgical removal of an entire lung and is usually performed as a cancer treatment. There are two types of pneumonectomy:

1) traditional pneumonectomy, in which only the diseased lung is removed and;

2) extrapleural pneumonectomy (sometimes also called a pleuropneumonectomy) in which the lung is removed as well as areas of the diaphragm, and the covering of the heart.

The pneumonectomy used in cases of malignant mesothelioma. Malignant mesothelioma is a cancer of the pleura (the membrane lining the lungs) and therefore the pneumonectomy required to treat this disease, must remove not only the diseased lung, but a portion of the pericardium (the membrane covering the heart), part of the diaphragm and the parietal pleura (the membrane lining the chest cavity) on the same side of the chest. This procedure is called a extrapleural pneumonectomy.

Within the medical community there is a debate over the effectiveness of this surgery. The surgery itself is dangerous with nearly 5 to 10% of patients not surviving. However, new procedures have improved these odds in recent years. Advocates of the surgery, including an outspoken doctor in Boston believe it is the most effective way to treat mesothelioma. They point to 3 and 4 year survival rates in many patients who have had sucessful surgeries. Other doctors are not so sure and argue that this invasve procedure is not worth the risks, especially in older patients.

An extrapleural pneumonectomy is considered the best surgical option when a tumor is located in the middle of the lung and involves a significant portion of the pulmonary artery or veins. However, because the surgery is risky and diminishes half of a patient's breathing capacity surgeons usually regard it as a last option and will usually first consider a pleurectomy. A Pleurectomy is a more complicated procedure, but is lung sparing involving only the removal of the pleura. Which treatment is recommended depends on many factors, including the stage of the tumor.

Overall it is unclear if extra-pleural pneumonectomy provides significantly greater benefits than pleurectomy, and if either is significantly more effective than non-surgical options (there is debate).

Pleurectomy can be technically more difficult and complex than the extrapleural pneumonectomy. However, the mortality of pleurectomy is more favorable (1.5%-5% by an experienced surgeon) and though extrapleural pneumonectomy may appear to be more effective in removing more of the tumor by the en bloc resection, when performed early enough, pleurectomy is equally effective. In later stage mesothelioma, when there is a tumor invasion of the lung parenchyma, pleurectomy is no longer an option.

A recent study designed to compare the effectiveness of pleurectomy, and extra-pleural pneumonectomy reveal that neither was more effective than the other in extending survival rates. Rather, other factors seemed to determine how long people survived. These factors included the stage and cell type of the tumor, the gender of the patient, and the type of treatment(s) given in conjunction with the surgery.

Pleurectomy can provide symptomatic relief and sometimes the bulk of the tumor can be removed. It is often used in combination with other treatments, but its value is very limited if the tumor is near any vital organs. Additionally, it is a complex surgery, not performed by most surgeons. Most patients are referred to centers dedicated to such treatments. Many of these centers also specialize in other forms of mesothelioma treatment, either alone or in combination (multi-modal therapy).

Before any surgery is considered for the treatment of malignant mesothelioma, the patient's overall health must be carefully evaluated. Tests should be performed to make sure the patient has no metastasis disease (cancer spread to distant sites) and to evaluate the patient's lung and heart function. These operations are only possible if a patient is fit enough and has good heart and lung function. If the patient's heart and lung function is poor, the operation may do more harm than good. With mesothelioma, a patient's lungs are often compromised for several reasons. Pleural fluid build up and tumor mass caused by mesothelioma can compress the lung. Also, the patient's exposure to asbestos may have decreased lung function, which also decreases with age. In addition, some patients have a history of smoking cigarettes, which further decreases lung function, and may render both procedures non-options.

Mesothelioma Diagnostic Tests

maging tests allow doctors to see a picture of the area in question. These could include x-rays, CT scans (computed tomography), or MRI (magnetic resonance imaging).

A bronchoscopy or a mediastinoscopy uses a lighted tube to let the doctor look at the affected area.

Cytology tests the pleural fluid for malignant cells after doctors remove it using a needle. Medical experts consider this test to have limited value in diagnosing mesothelioma, because negative or inconclusive readings account for nearly 85 percent of all fluid tested. Even with a positive fluid report, many doctors prefer to perform a confirming tissue biopsy as long as it does not compromise the patient's health. Fluid samples may be taken with a needle and sent to the lab to see if cancer cells are present.

A doctor can perform a thoracoscopy or a laparoscopy to look directly at the tumor and to take a sample of tissue that a pathologist then examines. In these procedures, a doctor makes a small incision and uses a tiny video camera to look at the area in question.

During a needle biopsy, done under local anesthetic, a doctor inserts a large hollow needle through the skin and into the chest cavity. The doctor then rotates the needle and as the needle is taken out, the doctor can collect tissue samples. Because of the small sample size of the tissue, experts consider this type of biopsy to be only 25 to 60 percent accurate in diagnosing mesothelioma.

Experts consider the open biopsy the most accurate for mesothelioma diagnosis. It is the procedure of choice because it affords the pathologist a larger tissue sample. Surgeons perform open biopsies in hospitals under general anesthetic.

A doctor may want to do other tests as well. Doctors often encounter difficulties in diagnosing mesothelioma. In some cases a pathologist may use an electron microscope to look at cells in greater detail. If after thorough review a pathologist confirms a diagnosis of mesothelioma, the doctor may want to do further testing such as a PET scan to learn the stage or extent of disease. Knowing the stage helps the doctor form a treatment plan.

Mesothelioma Diagnosis

Diagnosing mesothelioma can be difficult because the disease is rare and many doctors may not be familiar with it. Additionally, early symptoms of mesothelioma can appear non-specific to both a patient and his or her doctor, and may lead to a delay in diagnosis. The symptoms can include pain in the lower back or at the side of the chest and shortness of breath. Less often, an individual can experience trouble swallowing, cough, fever, sweating, tiredness, and weight loss. See more on symptoms >>

Symptoms of peritoneal mesothelioma (affecting the lining of the abdominal cavity) include belly pain, weight loss, nausea and vomiting. Minor ailments can often cause these same symptoms. Sometimes resembling viral pneumonia, pleural mesothelioma (affecting the lining of the lungs) patients may suffer shortness of breath, chest pain and persistent cough. Some patients show no symptoms at all. Pleural effusion, or an accumulation of fluid between the lining of the lung and the chest cavity, represents one of the most common symptoms of mesothelioma. As the volume of fluid increases, shortness of breath, known as "dyspnea", and sometimes pain may occur. If you have worked with asbestos and you have any of these symptoms, you should see your doctor right away.

If reasons exist to suspect you might have Mesothelioma (particularly exposure to asbestos), a doctor will take your medical history and do a complete physical exam. Then the doctor can use one or more of the methods described below to determine if the disease is present.

A doctor diagnoses mesothelioma through a careful assessment of clinical and radiological findings proceeded by a confirming tissue biopsy. The doctor should review the patient's medical history, including history of asbestos exposure, followed by a complete physical examination, x-rays of the chest or abdomen, and lung function tests. The doctor may also order a CT scan or MRI at this time. If any of these preliminary tests indicate the presence of mesothelioma, a biopsy is performed to confirm this diagnosis.

A doctor may use a needle biopsy of the mass, or the removal and examination of the fluid surrounding the lung for diagnosis. Because these samples are sometimes inadequate as far as determining cell type (epithelial, sarcomatous, or mixed) or because of the unreliability of fluid diagnosis, a doctor may recommend open pleural biopsy. In a pleural biopsy procedure, a surgeon makes a small incision through the chest wall and inserts a thin, lighted tube called a thoracoscope into the chest between two ribs. The surgeon then removes a sample of tissue that a pathologist will review under a microscope. In a peritoneal biopsy, the doctor makes a small incision in the abdomen and inserts a peritoneoscope into the abdominal cavity. The following represents a list of diagnostic procedures that a doctor may use to determine whether mesothelioma exists.

Pleural Mesothelioma Cancer

Pleural mesothelioma is a rare form of cancer that affects the pleura or lining around the outside of the lungs. Its only known cause is asbestos exposure. It generally manifests itself twenty to forty years after exposure (minimum of 15 years) and tends to appear most often in men, 50 to 70 years old. In its malignant form is a very serious condition.

There are generally two types of pleural mesothelioma the first being 'diffuse and malignant' , and the second being 'localized and benign' . The first type is cancerous and is generally fatal within a year of diagnosis. The second type is generally not life threatening and can usually be removed through surgery.

Pleural mesothelioma is difficult to detect early on because its initial symptoms tend to be somewhat generic i.e. shortness of breath, chest pain, and coughing, and in some cases there are no initial symptoms. As the disease develops, however, symptoms become more acute. In some cases, pain develops in the abdomen, in others, a severe cough is developed or breathing becomes restrictive. Only with a CT scan or an X-ray will a doctor be able to detect the possible presence of mesothelioma. If possible tumors are detected generally the doctor will perform a procedure called a Thoracoscopy .

During this procedure a doctor makes an incision in the chest wall and passes an instrument called a thorascope between the ribs. The thorascope allows the doctor to look inside the chest cavity to see if there are any abnormalities. A procedure called thoracentesis in which fluid is drained from pleurum may also be done at this time and may serve two purposes: First, the fluid obtained in this process may be analyzed and may occasionally provide a diagnosis. Secondly, draining the fluid or pleural effusion as it is also called, will in many cases help alleviate symptoms such as pain and restricted breathing. Because fluid analysis alone is generally not sufficient to make a diagnosis, the doctor, who discovers abnormalities during the thoracoscopy, will usually require a tissue sample so that the cells of the tissue may be viewed under a microscope by a pathologist. This tissue sample is called a biopsy.

Once mesothelioma has been diagnosed, the next step is determining how far the illness has progressed so that an appropriate treatment plan may be devised. This is done by studying the imaging of MRIs or CT Scans and is known by doctors as 'staging' or rather determining what 'stage' the disease has reached. Doctors chart mesothelioma in five stages of development and will refer to mesothelioma in terms of these stages. i.e. Stage I mesothelioma, Stage II mesothelioma, etc. Stages II through V are considered advanced mesothelioma and typically removal of the cancer is no longer an option. In general, Mesothelioma is very difficult to treat. First its tumors appear in the membranes surrounding the chest cavity and abdominal cavity, than spread to the underlying organs. This type of growth makes a complete surgical removal of Mesothelioma very unlikely.

Therefore, surgery is one of three primary treatment options for malignant mesothelioma. There are two types of surgery; palliative and aggressive. With palliative surgery the goal is to relieve painful symptoms caused by fluid build up or painful pressure exerted by the tumor's growth. The goal is to improve the quality of life and not to cure the disease. This type of surgery includes Thoracentesis a procedure used to drain fluid.

In aggressive surgery, or extrapleural pneumonectomy, the goal is to remove as much of the tumor as possible and attempt a cure. This option will generally only be sought if the disease is in its earliest stage (stage I), and the patient is both relatively young and in good health. Because of the high post surgery mortality rate involved with this operation many hospitals do not perform it. Even when the patient survives the operation it is unlikely to have completely eliminated the tumor.

Radiation therapy is another treatment option and like surgery is a very difficult and risky procedure. The biggest dilemma for the treating doctor is deciding the amount of radiation to use. For while radiation may serve to reduce the cancer, if too great a dose is used, it may also adversely affect surrounding organs. Often radiation therapy is used in conjunction with surgery in the hope that it will eliminate remaining cancerous growths that could not be removed.

Chemotherapy is yet another treatment option and like the other treatments has had limited success in treating mesothelioma. In fact it still hasn't been shown definitively to prolong the life of the patient with malignant mesothelioma. Like Radiation Therapy it is often used after surgery in order to eliminate any cancerous growth that could not be removed during the operation.

The good news is that cancer research is on going and future treatments are being developed. In some cases newer techniques will be available for patients who have run out of other options. A technique called "combination chemotherapy" which uses different combinations of chemotherapy is currently being developed and has so far met with partial success. As far as new medications are concerned, Lovastatin, a cholesterol-lowering drug, was found to destroy mesothelioma cells and therefore might be effective used in conjunction with chemotherapy or radiation. Immunotherapy, treatments which stimulate the immune system to combat the mesothelioma are also being researched. Intracavitary chemotherapy, a technique by which chemotherapy drugs are introduced directly into the peritoneal or pleural space is being researched as well, and has been shown in some studies to be effective. Intracavitary radiation therapy (or Brachytherapy) is based on the same premise. Forms of multimodality therapy, (which refers to techniques combining radiation treatment, chemotherapy, and surgery) are also being researched. Orders of procedure are also being researched. i.e. some physicians are using chemotherapy before surgery as a way of reducing the tumor size. Gene therapy is another burgeoning area of research. An advanced technique called photodynamic therapy, that introduces light sensitive drugs to the tumor than exposes the tumor to light, is also being researched. The future holds a great deal of hope for cancer victims, and mesothelioma patients should always have "there ear to the ground" for the emergence of new techniques.

Alimta (Pemetrexed) Mesothelioma Treatment

In July 2002, The U.S. Food and Drug Administration and Eli Lilly Company announced that Alimta (pemetrexed) would be made available to patients with malignant pleural mesothelioma. The drug, a chemotherapy treatment is not fully FDA approved but will be made available to "qualified patients who have been diagnosed with malignant pleural mesothelioma and have not yet received treatment." The FDA allows Alimta to be used under a so-called "Expanded access program," that allows new treatments available to patients with diseases like mesothelioma, for which there is no other treatment or satisfactory alternative therapy. Under this program, patients with mesothelioma will be given access to Alimta while the FDA review process is going forward and the treatment is pending review.

The FDA agreed to allow patients use of Alimta under the "expanded access program" based on the initial results from clinical trials. The results of a Phase III trial discussed at the annual meeting of the American Society of Clinical Oncology, showed that patients treated with Alimta and cisplatin had better survival rates, had less pain and shortness of breath. Pemetrexed (Alimta) is a new antifolate, a type of drug that targets the folic acid metabolic pathway, inhibiting the availability of certain B complex vitamins. The downside, in the trial was that in some patients there was decrease in the number of white blood cells used to fight infections.

The clinical trial was the largest ever conducted in the US for a mesothelioma treatment.

The findings: Tumors shrank in 41 percent of patients on Alimta (pemetrexed) in combination cisplatin, a more common chemotherapy treatment. Cisplatin resulted reduced to tumors in 17 percent of patients receiving it. Patients on the Alimta (pemetrexed) cisplatin combination lived nearly three months longer than those on cisplatin alone.

According to lead author of the study, Nicholas J. Vogelzang, M.D., University of Chicago Cancer Research Center, "This is the largest clinical trial ever conducted in this disease and the 25 to 30 percent improvement in survival for patients on the combination therapy is the first time anyone has documented a significant improvement in patients treated for mesothelioma."

Under the current expanded access program, Alimta may be available free to patients who qualify. Additionally, patients with mesothelioma may be entitled to large settlements against employers or asbestos makers.

What is Malignant Mesothelioma?

Most cancers find their names in the part of the body where the cancer first starts. Malignant Mesothelioma originates in tissue that surrounds different organs inside the body. This tissue, called mesothelium, protects the lungs, heart and stomach by making a special fluid that allows the organs to move. This fluid makes it easier for the lungs to move when breathing, the heart to move when beating, and the stomach to move when digesting. Tumors can start in any of these places. These tumors can be benign (non-cancerous) or malignant (cancerous). The information that follows concerns only malignant tumors.

The National Cancer Institute (NCI) identifies malignant mesothelioma as a rare form of cancer. Doctors only diagnose two to three thousand cases per year in the United States, with men three to five times more than women likely to suffer from Malignant Mesothelioma. Although rare, the incidents of Malignant Mesothelioma appear to be increasing.

The NCI further describes Malignant Mesothelioma as "a disease in which cancer (malignant) cells are found in the sac lining the chest, the lining of the abdominal cavity or the lining around the heart." Doctors have identified three types of malignant mesothelioma. refers to a cancer of the lining of the lung (pleura). affects the lining of the abdominal cavity (peritoneum). While pericardial mesothelioma is a cancer of the lining surrounding the heart (pericardium). About three-fourths of mesotheliomas start in the chest cavity. Another 10 to 20 percent begin in the abdomen, while those starting around the heart are very rare.

Three main sub-types of mesotheliomas exist. Sub-types (or cell types) of mesothelioma include the epithelioid type. This type accounts for 50 to 70 percent of all mesotheliomas and has the best outlook for responding to treatment. The other two types, mixed/biphasic and sarcomatoid, are less common. In general, the treatments for all three are the same.

Although rare, Malignant Mesothelioma represents a serious health threat to those diagnosed. Because it often becomes advanced before symptoms appear the outlook is not as good as it is for cancers that doctors find earlier. About half of the patients whose doctors find and treated the cancer early will survive two years or more. The average survival time for all stages of Malignant Mesothelioma is about one year.

What Causes Malignant Mesothelioma?

The main risk factor for mesothelioma is contact with asbestos. A person breathes in asbestos fibers, which then travel to the ends of the small air passages, and reach the lining of the lungs. There they can damage the mesothelial cells or the lining of the lung cells. If swallowed, these fibers can also reach the lining of the abdominal cavity where they play a part in causing a cancer called peritoneal mesothelioma.
A latency period of 20 to 50 years or more between initial exposure and development of mesothelioma exists. While researchers document the average latency period as between 35 and 40 years, they have documented rare instances when the period was less than 20 years.

The chances of suffering from mesothelioma rise with the intensity and duration of exposure to asbestos; however, numerous cases of mesothelioma occurred among people with very little occupational exposure or household exposure. Cases exist of people getting mesothelioma 30 or 40 years after a summer job working construction, and housewives or children being exposed from work clothing.

Prior to the mid-1970's, most insulation materials contained asbestos. Many other construction materials also contained asbestos, including, pipe insulation, boiler insulation, fireproofing spray, firebrick and gunnite (used for internal insulation of furnaces and boilers), roof, floor and ceiling tiles, transite siding, and brakes and clutches.

Because occupational exposure to asbestos often accounts for the most prolonged and intense exposure to asbestos, many people who worked with asbestos now suffer from mesothelioma. Among those trades in which a risk of asbestos exposure existed are insulators who installed asbestos insulation, boilermakers who constructed massive boilers filled with asbestos insulation, plumbers, pipefitters and steamfitters who fitted and welded pipes together and often worked in small unventilated compartments in ships where large quantities of insulation were used, plasterers who worked with fireproofing spray on steel beams, shipyard workers, electricians and mechanics, bricklayers, millwrights, carpenters, steel workers, refinery and industrial workers, and maintenance workers.