اضغط المربع الاسود للرابط مباشره

Insomnia

2009-03-17T13:15:00.000-07:00

Rumors have been flying that Angelina Jolie and Brad Pitt plan to tie the knot this weekend.
According to TheBosh.com, The word on the street is that we�ll soon be hearing wedding bells for Brad Pitt and Angelina Jolie.

فضائح المشاهير اضغط المربع الاسود اول الصفحه للرابط مباشره

2009-03-15T13:16:00.000-07:00

Where is Obama's Leadership?

2009-02-09T11:34:00.000-08:00

As the markets plummet and the value of my house and investments disappear where is my
candidate? Like everyone else, my anger is mounting with plenty of blame to go around. But where is Obama's leadership?

Fine, he should keep his calm and collected demeanor, but nonethless work furiously to bring the Democratic rebels in Congress in line and pass the compromise rescue plan without the need
for those fringe Republican ideologues. Why doesn't Obama go round up Bill and Hillary -- the other most influential leaders of the Democratic Party -- mobilize his enormous e-network and for good measure bring on board the gurus of high and low finance -- Warren Buffet and Suze Orman -- for a full court press?

Thanks to the hard negotiating of the Democratic Congressional leadership, the Paulson plan has a large investment element where the public gets equity warrants-- the government would be buying assets at rock bottom prices likely to make a profit later. For this reason Suze Orman calls it an "investment plan" not a bailout. Its what Sweden did in their banking and credit crisis just over a decade ago, and the taxpayer has made out fine.

There are many reasons we are where we are -- low interest rates, macroeconomic stability, plenty of global capital sloshing around, the deregulation regime since the Reagan days and, it must be said, the American consumer out of control.

But you can't fix 20 years worth of Wall St. manipulation and consumer indiscipline overnight. And yes the plan is not a panacea and has problems, etc.

Politics is the art of the possible. This deal just voted down is what's possible. The only
possibility now is to revive it with the requisite votes from the Democratic side.

Obama needn't drop his campaign to focus on the crisis. Rescuing the rescue plan ought
to be his campaign. Its leadership the country is looking for. Let's see some.

Anxiolytic

2009-01-25T11:21:00.000-08:00

An anxiolytic (or antianxiety agent) is a drug prescribed for the treatment of symptoms of anxiety. Some anxiolytics have been shown to be useful in the treatment of anxiety disorders as have antidepressants such as the class of selective serotonin reuptake inhibitors (SSRIs).
Though not anxiolytics, beta-receptor blockers such as propranolol and oxprenolol can be used to combat the somatic symptoms of anxiety.
Anxiolytics are also known as "minor tranquilizers", though this usage is less common in modern texts.
Types of anxiolytics
Anxiolytics are generally divided into two groups of medication, benzodiazepines and non-benzodiazepines.
Benzodiazepines
• Main article: Benzodiazepine
Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety. Common medications are lorazepam (Ativan), clonazepam (Klonopin), alprazolam (Xanax), and diazepam (Valium). Benzodiazepines may also be indicated to cover the latent periods associated with the medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide variety of conditions and symptoms and are usually a first choice when short-term CNS sedation is needed. Longer term uses include treatment for severe anxiety. There is a risk of a benzodiazepine withdrawal and rebound syndrome after continuous usage past two weeks. There is also the added problem of the accumulation of drug metabolites and adverse effects.
Benzodiazepines exert their anxiolytic properties at moderate dosage. At higher dosage hypnotic properties occur.
Serotonin 1A agonists
Buspirone (BuSpar) is a serotonin 1A agonist. It lacks the sedation and the dependence associated with benzodiazepines and causes much less cognitive impairment. It may be less effective than benzodiazepines in patients who have been previously treated with benzodiazepines as the medication does not provide the sedation that these patients may expect or equate with anxiety relief.
Barbiturates
Barbiturates and meprobamate exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and addiction is high. Many experts consider these drugs as obsolete for treating anxiety, although they may be valuable for the short term treatment of severe insomnia, only after benzodiazepines or non-benzodiazepines have failed. They are rarely prescribed anymore.
Hydroxyzine
Hydroxyzine (Atarax) is an old antihistamine originally approved for clinical use by the FDA in 1956. It possesses anxiolytic properties in addition to its antihistamine properties and is also licensed for the treatment of anxiety and tension. It is also used for its sedative properties as a premed before anesthesia or to induce sedation after anesthesia. It has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder while producing less side effects.
Herbal treatments
Certain herbs, such as valerian, kava (Kava Kava), chamomile, Kratom, Blue Lotus extracts, Sceletium tortuosum (kanna), Common Skullcap and bacopa monniera are reputed to have anxiolytic properties. With the exception of kava kava, only limited evidence exists for their efficacy.
A team from Brazil found cannabidiol (a constituent of marijuana; also called CBD) to be an effective anti-psychotic and anxiolytic. "CBD induced a clear anxiolytic effect and a pattern of cerebral activity compatible with anxiolytic activity. Therefore, similar to the data obtained in animal models, results from studies on healthy volunteers have strongly suggested an anxiolytic-like effect of CBD."
Pineapple sage, or salvia elegans, is used as a treatment for anxiety in traditional Mexican medicine, and a preliminary study on mice has yielded some support for both anxiolytic and antidepressant properties.
Over-The-Counter
Chlorpheniramine is the only over the counter medication reported to have some very mild anxiolytic properties (off-label use). The drug is approved by the FDA for allergies, rhinitis, and urticaria.
Alternatives to medication
Psychotherapy (e.g. cognitive or behavior therapy) is often useful as an adjunct to medication or as an alternative to medication. Research has demonstrated better long-term results for anxiety when treated with psychotherapy as opposed to pharmacotherapy alone.

Antipsychotics

2009-01-25T11:11:00.000-08:00

Antipsychotics are a group of psychoactive drugs commonly but not exclusively used to treat psychosis, which is typified by schizophrenia. Over time a wide range of antipsychotics have been developed. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s. Most of the drugs in the second generation, known as atypical antipsychotics, have more recently been developed. Both classes of medication tend to block receptors in the brain's dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets. A number of side effects have been observed in relation to specific medications, including weight gain, agranulocytosis, tardive dyskinesia, tardive akathisia and tardive psychoses. The development of new antipsychotics, and the relative efficacy of different ones, is an important ongoing field of research. Antipsychotic medication is not generally regarded as a good treatment, just the best available. The most appropriate drug for an individual patient requires careful consideration.
Terminology
Antipsychotics are also referred to as neuroleptic drugs . The word neuroleptic is derived from Greek: "νεύρον" (originally meaning sinew but today referring to the nerves) and "λαμβάνω" (meaning take hold of). Thus, the word means taking hold of one's nerves. This term reflects the drugs' ability to make movement more difficult and sluggish, which clinicians previously believed indicated that a dose was high enough.[citation needed] The lower doses used currently have resulted in reduced incidence of motor side effects and sedation, and the term is less commonly used than in the past..
Antipsychotics are broadly divided into two groups, the typical or first-generation antipsychotics and the atypical or second-generation antipsychotics. There are also dopamine partial agonists, which are often categorized as atypicals.
Typical antipsychotics are also sometimes referred to as tranquilizers, because some of them can tranquilize and sedate. This term is increasingly disused, as the terminology implies a connection with benzodiazepines ("minor" tranquilizers) when none exists.
Usage
Common conditions with which antipsychotics might be used include schizophrenia, mania, and delusional disorder. They might be used to counter psychosis associated with a wide range of other diagnoses, such as psychotic depression. In addition, these drugs are used to treat non-psychotic disorders. For example, some antipsychotics (haloperidol, pimozide) are used off-label to treat Tourette syndrome, whereas Aripiprazole is prescribed in some cases of Asperger's syndrome.
History
The original antipsychotic drugs were happened upon largely by chance and were tested empirically for their effectiveness. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. It was first used on psychiatric patients because of its powerful calming effect; at the time it was regarded as a "chemical lobotomy". Lobotomy was used to treat many behavioral disorders, including psychosis, although its "effectiveness" was (from a modern viewpoint) due to its tendency to markedly reduce behavior of all types. However, chlorpromazine quickly proved to reduce the effects of psychosis in a more effective and specific manner than the extreme lobotomy-like sedation it was known for.
The underlying neurochemistry involved has since been studied in detail, and subsequent anti-psychotic drugs have been discovered by an approach that incorporates this sort of information.
Common antipsychotics

Chlorpromazine.

Haloperidol.

Quetiapine.
Commonly used antipsychotic medications are listed below by drug group. Trade names appear in parentheses.
First generation antipsychotics
Butyrophenones
• Haloperidol (Haldol)
Phenothiazines
• Chlorpromazine (Thorazine)
• Fluphenazine (Prolixin) - Available in decanoate (long-acting) form
• Perphenazine (Trilafon)
• Prochlorperazine (Compazine)
• Thioridazine (Mellaril)
• Trifluoperazine (Stelazine)
• Mesoridazine
• Promazine
• Triflupromazine (Vesprin)
• Levomepromazine (Nozinan)
• Promethazine (Phenergan)
Thioxanthenes
• Chlorprothixene
• Flupenthixol (Depixol and Fluanxol)
• Thiothixene (Navane)
• Zuclopenthixol (Clopixol & Acuphase)
Second generation antipsychotics
• Clozapine (Clozaril) - Requires weekly to biweekly CBC (FBC) because of risk of agranulocytosis (a severe decrease of white blood cells).
• Olanzapine (Zyprexa) - Used to treat psychotic disorders including schizophrenia, acute manic episodes, and maintenance of bipolar disorder. Dosing 2.5 to 20 mg per day. Comes in a form that quickly dissolves in the mouth (Zyprexa Zydis). May cause appetite increase, weight gain, and altered glucose metabolism leading to an increased risk of diabetes mellitus.
• Risperidone (Risperdal) - Dosing 0.25 to 6 mg per day and is titrated upward; divided dosing is recommended until initial titration is completed, at which time the drug can be administered once daily. Available in long-acting form (Risperdal Consta that is administered every 2 weeks; usual dose is 25 mg). Comes in a form that quickly dissovles in the mouth (Risperdal M-Tab). Used off-label to treat Tourette Syndrome or Anxiety Disorder.
• Quetiapine (Seroquel) - Used primarily to treat bipolar disorder and schizophrenia, and "off-label" to treat chronic insomnia and restless legs syndrome; it is a powerful sedative (if it is used to treat sleep disorders and is not effective at 200 mg, it is not going to be effective in this regard). Dosing starts at 25 mg and continues up to 800 mg maximum per day, depending on the severity of the symptom(s) being treated. Users typically take smaller doses during the day for the neuroleptic properties and larger dose at bedtime for the sedative effects, or divided in two equal high doses every 12 hours (75 - 400 mg bid).
• Ziprasidone (Geodon) - Now (2006) approved to treat bipolar disorder. Dosing 20 mg twice daily initially up to 80 mg twice daily. Prolonged QT interval a concern; watch closely with patients that have heart disease; when used with other drugs that prolong QT interval potentially life-threatening.
• Amisulpride (Solian) - Selective dopamine antagonist. Higher doses (greater than 400 mg) act upon post-synaptic dopamine receptors resulting in a reduction in the positive symptoms of schizophrenia, such as psychosis. Lower doses, however, act upon dopamine autoreceptors, resulting in increased dopamine transmission, improving the negative symptoms of schizophrenia. Lower doses of amisulpride have also been shown to have anti-depressant and anxiolytic effects in non-schizophrenic patients, leading to its use in dysthymia and social anxiety disorder. In one particular study, amisulpride was found to have greater efficacy than fluoxetine in decreasing anxiety. At present, amisulpride is approved in Europe, Australia, and other countries for use in schizophrenia, and is approved and marketed in lower dosages in some countries for treating dysthymia (such as in Italy as Deniban). Amisulpride has not been approved by the FDA for use in the United States.
• Asenapine is a 5-HT2A- and D2-receptor antagonist under development for the treatment of schizophrenia and acute mania associated with bipolar disorder.
• Paliperidone (Invega) - Derivative of risperidone. Approved in December 2006.
Third generation antipsychotics
• Aripiprazole (Abilify) - Dosing 1 mg up to maximum of 30 mg has been used. Mechanism of action is thought to reduce susceptibility to metabolic symptoms seen in some other atypical antipsychotics.
• Dopamine partial agonists:
• Under clinical development - Bifeprunox; norclozapine (ACP-104).
Other options
• Tetrabenazine (Nitoman in Canada and Xenazine in New Zealand and some parts of Europe) is similar in function to antipsychotic drugs, though is not, in general, considered an antipsychotic itself. This is likely due to its main usefulness being the treatment of hyperkinetic movement disorders such as Huntington's Disease and Tourette syndrome, rather than for conditions such as schizophrenia. Also, rather than having the potential to cause tardive dyskinesia, which most antipsychotics have, tetrabenazine can actually be an effective treatment for the condition.
• Cannabidiol One of the main psychoactive components of cannabis. A recent study has shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia.
The most common typical antipsychotic drugs are now off-patent, meaning any pharmaceutical company is legally allowed to produce generic versions of these medications. While this makes them cheaper than the atypical drugs that are still manufactured under patent constraints, atypical drugs are preferred as a first-line treatment because they are believed to have fewer side effects and seem to have additional benefits for the 'negative symptoms' of schizophrenia, a typical condition for which they might be prescribed.
Metabotropic glutamate receptor 2 agonism has been seen as a promising strategy in the development of novel antipsychotics. When tested in patients, the research substance LY2140023 yielded promising results and had few side effects. The active metabolite of this prodrug targets the brain glutamate receptors mGluR2/3 rather than dopamine receptors. It is currently in phase-2 clinical testing (2007).
Drug action
All antipsychotic drugs tend to block D2 receptors in the dopamine pathways of the brain. This means that dopamine released in these pathways has less effect. Excess release of dopamine in the mesolimbic pathway has been linked to psychotic experiences. It is the blockade of dopamine receptors in this pathway that is thought to control psychotic experiences.
Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects that the typical antipsychotics can produce (see below). They were commonly classified on a spectrum of low potency to high potency, where potency referred to the ability of the drug to bind to dopamine receptors, and not to the effectiveness of the drug. High-potency antipsychotics such as haloperidol, in general, have doses of a few milligrams and cause less sleepiness and calming effects than low-potency antipsychotics such as chlorpromazine and thioridazine, which have dosages of several hundred milligrams. The latter have a greater degree of anticholinergic and antihistaminergic activity, which can counteract dopamine-related side effects.
Atypical antipsychotic drugs have a similar blocking effect on D2 receptors. Some also block or partially block serotonin receptors (particularly 5HT2A, C and 5HT1A receptors):ranging from risperidone, which acts overwhelmingly on serotonin receptors, to amisulpride, which has no serotonergic activity. The additional effects on serotonin receptors may be why some of them can benefit the 'negative symptoms' of schizophrenia.
Side effects
Antipsychotics are associated with a range of side effects. It is well-recognized that many stop taking them (around two-thirds of people in controlled drug trials) due in part to adverse effects. Extrapyramidal reactions include tardive psychosis, acute dystonias, akathisia, parkinsonism (rigidity and tremor), tardive dyskinesia, tachycardia, hypotension, impotence, lethargy, seizures, intense dreams or nightmares, and hyperprolactinaemia.
From a subjective perspective, antipsychotics heavily influence one's perceptions of pleasurable sensations, causing a severe reduction in feelings of desire, motivation, pensive thought, and awe. This does not coincide with the apathy and lack of motivation experienced by the negative symptoms of schizophrenia. Detrimental effects on short term memory, which affect the way one figures and calculates (although this also may be purely subjective), may also be observed on high enough dosages. These are all the reasons why they are thought to affect "creativity". Also, for some individuals with schizophrenia, too much stress may cause "relapse".
Following are details concerning some of the side effects of antipsychotics:
• Antipsychotics, particularly atypicals, appear to cause diabetes mellitus and fatal Diabetic ketoacidosis, especially (in US studies) in African Americans.
• Antipsychotics may cause pancreatitis.
• The atypical antipsychotics (especially olanzapine) seem to cause weight gain more commonly than the typical antipsychotics. The well-documented metabolic side effects associated with weight gain include diabetes, which can be life-threatening.
• Clozapine also has a risk of inducing agranulocytosis, a potentially dangerous reduction in the number of white blood cells in the body. Because of this risk, patients prescribed clozapine may need to have regular blood checks to catch the condition early if it does occur, so the patient is in no danger.[citation needed]
• One of the more serious of these side effects is tardive dyskinesia, in which the sufferer may show repetitive, involuntary, purposeless movements often of the lips, face, legs, or torso. It is believed that there is a greater risk of developing tardive dyskinesia with the older, typical antipsychotic drugs, although the newer antipsychotics are now also known to cause this disorder.
• A potentially serious side effect of many antipsychotics is that they tend to lower an individual's seizure threshold. Chlorpromazine and clozapine, in particular, have a relatively high seizurogenic potential. Fluphenazine, haloperidol, pimozide and risperidone exhibit a relatively low risk. Caution should be exercised in individuals that have a history of seizurogenic conditions such as epilepsy, or brain damage.
• Another antipsychotic side effect is deterioration of teeth due to a lack of saliva.[citation needed]
• Another serious side effect is neuroleptic malignant syndrome, in which the drugs appear to cause the temperature regulation centers to fail, resulting in a medical emergency, as the patient's temperature suddenly increases to dangerous levels.
• Another problematic side effect of antipsychotics is dysphoria.
• Following controversy over possible increased mortality (death) related to antipsychotics in indivdiuals with Alzheimers, warnings have been added to packaging.
Some people suffer few apparent side effects from taking antipsychotic medication, whereas others may have serious adverse effects. Some side effects, such as subtle cognitive problems, may go unnoticed.
There is a possibility that the risk of tardive dyskinesia can be reduced by combining the anti-psychotics with diphenhydramine or benztropine, although this remains to be established. Central nervous system damage is also associated with irreversible tardive akathisia and/or tardive dysphrenia.
Structural effects
Many studies now indicate that chronic treatment with antipsychotics affects the brain at a structural level, for example increasing the volume of the basal ganglia (especially the caudate nucleus), and reducing cortical grey matter volume in different brain areas. The effects may differ for typical versus atypical antipsychotics and may interact with different stages of disorders. Death of neurons in the cerebral cortex, especially in women, has been linked to the use of both typical and atypical antipsychotics for individuals with Alzheimers.
Recent studies on macaque monkeys have found that administration of haloperidol or olanzapine for about two years led to a significant overall shrinkage in brain tissue, in both gray and white matter across several brain areas, with lower glial cell counts, due to a decrease in astrocytes and oligodendrocytes, and increased neuronal density. It has been said that these studies require serious attention and that such effects were not clearly tested for by pharmaceutical companies prior to obtaining approval for placing the drugs on the market.
Efficacy
There have been a large number of studies of the efficacy of typical antipsychotics, and an increasing number on the more recent atypical antipsychotics.
The American Psychiatric Association and the UK National Institute for Health and Clinical Excellence recomme They state that response to any given antipsychotic can be variable so that trials may be necessary, and that lower doses are to be preferred where possible.
Antipsychotic polypharmacy—prescribing two or more antipsychotics at the same time for an individual—is said to be a frequent practice but not necessarily evidence-based.
Some doubts have been raised about the long-term effectiveness of antipsychotics because two large international World Health Organization studies found individuals diagnosed with schizophrenia tend to have better long-term outcomes in developing countries (where there is lower availability and use of antipsychotics) than in developed countries. The reasons for the differences are not clear, however, and various explanations have been suggested.
Some argue that the evidence for antipsychotics from withdrawal-relapse studies may be flawed, because they do not take into account that antipsychotics may sensitize the brain and provoke psychosis if discontinued. Evidence from comparison studies indicates that at least some individuals recover from psychosis without taking antipsychotics, and may do better than those that do take antipsychotics.Some argue that, overall, the evidence suggests that antipsychotics only help if they are used selectively and are gradually withdrawn as soon as possible.
A dose response effect has been found in one study from 1971 between increasing neuroleptic dose and increasing number of psychotic breaks.[26][verification needed]
Typical versus atypical
While the atypical, second-generation medications were marketed as offering greater efficacy in reducing psychotic symptoms while reducing side effects (and extra-pyramidal symptoms in particular) than typical medications, the results showing these effects often lack robustness. To remediate this problem, the NIMH conducted a recent multi-site, double-blind study (the CATIE project), which was published in 2005. This study compared several atypical antipsychotics to an older typical antipsychotic, perphenazine, among 1493 persons with schizophrenia. Perphenazine was chosen because of its lower potency and moderate side effect profile. The study found that only olanzapine outperformed perphenazine in the researchers' principal outcome, the discontinuation rate. The authors also noted the apparent superior efficacy of olanzapine to the other drugs for greater reduction in psychopathology, longer duration of successful treatment, and lower rate of hospitalizations for an exacerbation of schizophrenia. In contrast, no other atypical studied (risperidone, quetiapine, and ziprasidone) did better than the typical perphenazine on those measures. Olanzapine, however, was associated with relatively severe metabolic effects: Subjects with olanzapine showed a major weight gain problem and increases in glucose, cholesterol, and triglycerides. The average weight gain (1.1 kg/month, or 44 pounds for the 18 months that the study lasted) casts serious doubt on the potentiality of long-term use of this drug. Perphenazine did not create more extrapyramidal side effects as measured by rating scales (a result supported by a meta-analysis by Dr. Leucht published in Lancet), although more patients discontinued perphenazine owing to extrapyramidal effects compared to the atypical agents (8 percent vs. 2 percent to 4 percent, P=0.002).
A phase 2 part of this study roughly replicated these findings. This phase consisted of a second randomization of the patients that discontinued taking medication in the first phase. Olanzapine was again the only medication to stand out in the outcome measures, although the results did not always reach statistical significance, due in part to the decrease of power. Perphenazine again did not create more extrapyramidal effects.
A subsequent phase was conducted. This phase allowed clinicians to offer clozapine which was more effective at reducing medication drop-outs than other neuroleptic agents. However, the potential for clozapine to cause toxic side effects, including agranulocytosis, limits its usefulness.

cancer

2009-01-23T11:57:00.000-08:00

Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age.[1] Cancer causes about 13% of all deaths.[2] According to the American Cancer Society, 7.6 million people died from cancer in the world during 2007.[3] Cancers can affect all animals.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers are usually affected by complex interactions between carcinogens and the host's genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly recognized as important.

Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.
Contents
[hide]

* 1 Classification
o 1.1 Nomenclature
o 1.2 Adult cancers
o 1.3 Child cancers
o 1.4 Infant cancers
* 2 Signs and symptoms
* 3 Diagnosis
o 3.1 Investigation
o 3.2 Biopsy
* 4 Treatment
o 4.1 Surgery
o 4.2 Radiation therapy
o 4.3 Chemotherapy
o 4.4 Targeted therapies
o 4.5 Immunotherapy
o 4.6 Hormonal therapy
o 4.7 Angiogenesis inhibitors
o 4.8 Symptom control
o 4.9 Treatment trials
o 4.10 Complementary and alternative
* 5 Prognosis
o 5.1 Emotional impact
* 6 Causes
o 6.1 Mutation: chemical carcinogens
o 6.2 Mutation: ionizing radiation
o 6.3 Viral or bacterial infection
o 6.4 Hormonal imbalances
o 6.5 Immune system dysfunction
o 6.6 Heredity
o 6.7 Other causes
* 7 Pathophysiology
o 7.1 Epigenetics
o 7.2 Oncogenes
o 7.3 Tumor suppressor genes
o 7.4 Cancer cell biology
+ 7.4.1 Clonal evolution
+ 7.4.2 Biological properties of cancer cells
* 8 Prevention
o 8.1 Modifiable ("lifestyle") risk factors
o 8.2 Diet
o 8.3 Vitamins
o 8.4 Chemoprevention
o 8.5 Genetic testing
o 8.6 Vaccination
o 8.7 Screening
* 9 Epidemiology
* 10 History
* 11 Research
* 12 See also
* 13 References
o 13.1 General references
* 14 External links
o 14.1 Professional and research
o 14.2 Support and advocacy

Classification

Cancer is generally classified according to the tissue from which the cancerous cells originate, the primary tumor, as well as the normal cell type they most resemble. These are location and histology, respectively.

Nomenclature

The following closely related terms may be used to designate abnormal growths:

* Tumor or tumour: originally, it meant any abnormal swelling, lump or mass. In current English, however, the word tumor has become synonymous with neoplasm, specifically solid neoplasm. Note that some neoplasms, such as leukemia, do not form tumors.
* Neoplasm: the scientific term to describe an abnormal proliferation of genetically altered cells. Neoplasms can be benign or malignant:
o Malignant neoplasm or malignant tumor: synonymous with cancer.
o Benign neoplasm or benign tumor: a tumor (solid neoplasm) that stops growing by itself, does not invade other tissues and does not form metastases.
* Invasive tumor is another synonym of cancer. The name refers to invasion of surrounding tissues.
* Pre-malignancy, pre-cancer or non-invasive tumor: A neoplasm that is not invasive but has the potential to progress to cancer (become invasive) if left untreated. These lesions are, in order of increasing potential for cancer, atypia, dysplasia and carcinoma in situ.

The following terms can be used to describe a cancer:

* Screening: a test done on healthy people to detect tumors before they become apparent. A mammogram is a screening test.
* Diagnosis: the confirmation of the cancerous nature of a lump. This usually requires a biopsy or removal of the tumor by surgery, followed by examination by a pathologist.
* Surgical excision: the removal of a tumor by a surgeon.
o Surgical margins: the evaluation by a pathologist of the edges of the tissue removed by the surgeon to determine if the tumor was removed completely ("negative margins") or if tumor was left behind ("positive margins").
* Grade: a number (usually on a scale of 3) established by a pathologist to describe the degree of resemblance of the tumor to the surrounding benign tissue.
* Stage: a number (usually on a scale of 4) established by the oncologist to describe the degree of invasion of the body by the tumor.
* Recurrence: new tumors that appear at the site of the original tumor after surgery.
* Metastasis: new tumors that appear far from the original tumor.
* Transformation: the concept that a low-grade tumor transforms to a high-grade tumor over time. Example: Richter's transformation.
* Chemotherapy: treatment with drugs.
* Radiation therapy: treatment with radiations.
* Adjuvant therapy: treatment, either chemotherapy or radiation therapy, given after surgery to kill the remaining cancer cells.
* Prognosis: the probability of cure after the therapy. It is usually expressed as a probability of survival five years after diagnosis. Alternatively, it can be expressed as the number of years when 50% of the patients are still alive. Both numbers are derived from statistics accumulated with hundreds of similar patients to give a Kaplan-Meier curve.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:

* Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
* Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
* Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells
* Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
* Blastic tumor or blastoma: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.

Malignant tumors (cancers) are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer of the liver is called hepatocarcinoma; a cancer of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid). Unfortunately, some cancers also use the -oma suffix, examples being melanoma and seminoma.

Adult cancers

In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.[4] On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and may vary substantially in other countries:
Male Female
most common (by occurrence) most common (by mortality)[4] most common (by occurrence) most common (by mortality)[4]
prostate cancer (33%) lung cancer (31%) breast cancer (32%) lung cancer (27%)
lung cancer (13%) prostate cancer (10%) lung cancer (12%) breast cancer (15%)
colorectal cancer (10%) colorectal cancer (10%) colorectal cancer (11%) colorectal cancer (10%)
bladder cancer (7%) pancreatic cancer (5%) endometrial cancer (6%) ovarian cancer (6%)
cutaneous melanoma (5%) leukemia (4%) non-Hodgkin lymphoma (4%) pancreatic cancer (6%)

Child cancers

Cancer can also occur in young children and adolescents, but it is rare (about 150 cases per million yearly in the US). Statistics from the SEER program of the US NCI demonstrate that childhood cancers increased 19% between 1975 and 1990, mainly due to an increased incidence in acute leukemia. Since 1990, incidence rates have decreased.[5]

Children living near nuclear facilities face an increased risk of cancer.[6]

Infant cancers

The age of peak incidence of cancer in children occurs during the first year of life, in infants. The average annual incidence in the United States, 1975-1995, was 233 per million infants.[5] Several estimates of incidence exist. According to SEER,[5] in the United States:

* Neuroblastoma comprised 28% of infant cancer cases and was the most common malignancy among these young children (65 per million infants).
* The leukemias as a group (41 per million infants) represented the next most common type of cancer, comprising 17% of all cases.
* Central nervous system malignancies comprised 13% of infant cancer, with an average annual incidence rate of nearly 30 per million infants.
* The average annual incidence rates for malignant germ cell and malignant soft tissue tumors were essentially the same at 15 per million infants. Each comprised about 6% of infant cancer.

According to another study:[4]

* Leukemia (usually ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma.

Teratoma (a germ cell tumor) often is cited as the most common tumor in this age group, but most teratomas are surgically removed while still benign, hence not necessarily cancer. Prior to the widespread routine use of prenatal ultrasound examinations, the incidence of sacrococcygeal teratomas diagnosed at birth was 25 to 29 per million births.

Female and male infants have essentially the same overall cancer incidence rates, a notable difference compared to older children.

White infants have higher cancer rates than black infants. Leukemias accounted for a substantial proportion of this difference: the average annual rate for white infants (48.7 per million) was 66% higher than for black infants (29.4 per million).[5]

Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.

Signs and symptoms
Symptoms of cancer metastasis depend location of the tumor.

Roughly, cancer symptoms can be divided into three groups:

* Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice (yellowing the eyes and skin).
* Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.
* Systemic symptoms: weight loss, poor appetite, fatigue and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

Diagnosis

Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician (medical doctor) who specializes in the diagnosis of cancer and other diseases.

Investigation
Chest x-ray showing lung cancer in the left lung.

People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

Biopsy

A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about future behavior of the cancer (prognosis) and best treatment.

Treatment

Main article: cancer treatment

Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A number of experimental cancer treatments are also under development.

Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.

Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.

Surgery

In theory, non-hematological cancers can be cured if entirely removed by surgery, but this is not always possible. When the cancer has metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.

Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy.

Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Radiation therapy

Main article: Radiation therapy

Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via external beam radiotherapy (EBRT) or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.

Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Chemotherapy

Main article: Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous stem cell transplantation. Alternatively, hematopoietic stem cells may be transplanted from a matched unrelated donor (MUD).

Targeted therapies

Main article: Targeted therapy

Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib (Gleevec/Glivec) and gefitinib (Iressa).

Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies.

Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to this peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.

Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors.[7]

Immunotherapy

Main article: Cancer immunotherapy

Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumours include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Vaccines to generate specific immune responses are the subject of intensive research for a number of tumours, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells.

Allogeneic hematopoietic stem cell transplantation ("bone marrow transplantation" from a genetically non-identical donor) can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.

Hormonal therapy

Main article: Hormonal therapy (oncology)

The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Removing or blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial.

Angiogenesis inhibitors

Main article: Angiogenesis inhibitor

Angiogenesis inhibitors prevent the extensive growth of blood vessels (angiogenesis) that tumors require to survive. Some, such as bevacizumab, have been approved and are in clinical use. One of the main problems with anti-angiogenesis drugs is that many factors stimulate blood vessel growth in cells normal or cancerous. Anti-angiogenesis drugs only target one factor, so the other factors continue to stimulate blood vessel growth. Other problems include route of administration, maintenance of stability and activity and targeting at the tumor vasculature.[8]

Symptom control

Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. Although doctors generally have the therapeutic skills to reduce pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of palliative care has arisen specifically in response to the symptom control needs of this group of patients.

Pain medication, such as morphine and oxycodone, and antiemetics, drugs to suppress nausea and vomiting, are very commonly used in patients with cancer-related symptoms. Improved antiemetics such as ondansetron and analogues, as well as aprepitant have made aggressive treatments much more feasible in cancer patients.

Chronic pain due to cancer is almost always associated with continuing tissue damage due to the disease process or the treatment (i.e. surgery, radiation, chemotherapy). Although there is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, these are not usually the predominant etiologic factors in patients with cancer pain. Furthermore, many patients with severe pain associated with cancer are nearing the end of their lives and palliative therapies are required. Issues such as social stigma of using opioids, work and functional status, and health care consumption are not likely to be important in the overall case management. Hence, the typical strategy for cancer pain management is to get the patient as comfortable as possible using opioids and other medications, surgery, and physical measures. Doctors have been reluctant to prescribe narcotics for pain in terminal cancer patients, for fear of contributing to addiction or suppressing respiratory function. The palliative care movement, a more recent offshoot of the hospice movement, has engendered more widespread support for preemptive pain treatment for cancer patients.

Fatigue is a very common problem for cancer patients, and has only recently become important enough for oncologists to suggest treatment, even though it plays a significant role in many patients' quality of life.

Treatment trials

Main article: Experimental cancer treatment

Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Patients who take part may be helped personally by the treatment they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. At the same time, new treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit. There is no guarantee that a new treatment being tested or a standard treatment will produce good results. In children with cancer, a survey of trials found that those enrolled in trials were on average not more likely to do better or worse than those on standard treatment; this confirms that success or failure of an experimental treatment cannot be predicted.[9]

Complementary and alternative

Main article: Unproven cancer therapy

Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine.[10] "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine.[11] CAM use is common among people with cancer; a 2000 study found that 69% cancer patients had used at least one CAM therapy as part of their cancer treatment.[12] Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments which have been investigated and shown to be ineffective continue to be marketed and promoted.[13]

Prognosis

Cancer has a reputation for being a deadly disease. While this certainly applies to certain particular types, the truths behind the historical connotations of cancer are increasingly being overturned by advances in medical care. Some types of cancer have a prognosis that is substantially better than nonmalignant diseases such as heart failure and stroke.

Progressive and disseminated malignant disease has a substantial impact on a cancer patient's quality of life, and many cancer treatments (such as chemotherapy) may have severe side-effects. In the advanced stages of cancer, many patients need extensive care, affecting family members and friends. Palliative care solutions may include permanent or "respite" hospice nursing.

Emotional impact

Many local organizations offer a variety of practical and support services to people with cancer. Support can take the form of support groups, counseling, advice, financial assistance, transportation to and from treatment, films or information about cancer. Neighborhood organizations, local health care providers, or area hospitals may have resources or services available.

Counseling can provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, peer counseling, bereavement, patient-to-patient, and sexuality.

Many governmental and charitable organizations have been established to help patients cope with cancer. These organizations often are involved in cancer prevention, cancer treatment, and cancer research.

Causes

Main article: Carcinogenesis

Cancer is a diverse class of diseases which differ widely in their causes and biology. The common thread in all known cancers is the acquisition of abnormalities in the genetic material of the cancer cell and its progeny. Research into the pathogenesis of cancer can be divided into three broad areas of focus. The first area of research focuses on the agents and events which cause or facilitate genetic changes in cells destined to become cancer. Second, it is important to uncover the precise nature of the genetic damage, and the genes which are affected by it. The third focus is on the consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events, leading to further progression of the cancer.

Mutation: chemical carcinogens

Cancer pathogenesis is traceable back to DNA mutations that impact cell growth and metastasis. Substances that cause DNA mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. Tobacco smoking is associated with many forms of cancer,[14] and causes 90% of lung cancer.[15] Prolonged exposure to asbestos fibers is associated with mesothelioma.[16]

Many mutagens are also carcinogens, but some carcinogens are not mutagens. Alcohol is an example of a chemical carcinogen that is not a mutagen.[17] Such chemicals may promote cancers through stimulating the rate of cell division. Faster rates of replication leaves less time for repair enzymes to repair damaged DNA during DNA replication, increasing the likelihood of a mutation.
The incidence of lung cancer is highly correlated with smoking. Source:NIH.

Decades of research has demonstrated the link between tobacco use and cancer in the lung, larynx, head, neck, stomach, bladder, kidney, oesophagus and pancreas.[18] Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.[19] Tobacco is responsible for about one in three of all cancer deaths in the developed world,[14] and about one in five worldwide.[19] Indeed, lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men. However, the numbers of smokers worldwide is still rising, leading to what some organizations have described as the tobacco epidemic.[20]

Mutation: ionizing radiation

Sources of ionizing radiation, such as radon gas, can cause cancer. Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies.[21]

Radio-frequency radiation from mobile phones has been proposed as a cause of cancer, but there is little evidence of such a link.[22] Nevertheless, some experts caution against prolonged exposure.[23]

Viral or bacterial infection

Some cancers can be caused by infection with pathogens.[24] Many cancers originate from a viral infection; this is especially true in animals such as birds, but also in humans, as viruses are responsible for 15% of human cancers worldwide. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage.[25] The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely transforming viruses, the virus carries an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, the virus genome is inserts near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements then cause overexpression of that proto-oncogene. This induces uncontrolled cell division. Because the site of insertion is not specific to proto-oncogenes and the chance of insertion near any proto-oncogene is low, slowly-transforming viruses will cause tumors much longer after infection than the acutely-transforming viruses.

Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer in 0.47% of hepatitis B patients per year (especially in Asia, less so in North America), and in 1.4% of hepatitis C carriers per year. Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development. Worldwide, liver cancer is one of the most common, and most deadly, cancers due to a huge burden of viral hepatitis transmission and disease.

Advances in cancer research have made a vaccine designed to prevent cancer available. In 2006, the U.S. Food and Drug Administration approved a human papilloma virus vaccine, called Gardasil. The vaccine protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. In March 2007, the US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) officially recommended that females aged 11-12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization.

In addition to viruses, researchers have noted a connection between bacteria and certain cancers. The most prominent example is the link between chronic infection of the wall of the stomach with Helicobacter pylori and gastric cancer.[26][27] Although only a minority of those infected with Helicobacter go on to develop cancer, since this pathogen is quite common it is probably responsible for the majority of these cancers.[28]

Hormonal imbalances

Some hormones can act in a similar manner to non-mutagenic carcinogens in that they may stimulate excessive cell growth. A well-established example is the role of hyperestrogenic states in promoting endometrial cancer.

Immune system dysfunction

HIV is associated with a number of malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma, and HPV-associated malignancies such as anal cancer and cervical cancer. AIDS-defining illnesses have long included these diagnoses. The increased incidence of malignancies in HIV patients points to the breakdown of immune surveillance as a possible etiology of cancer.[29] Certain other immune deficiency states (e.g. common variable immunodeficiency and IgA deficiency) are also associated with increased risk of malignancy.[30]

Heredity

Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component, often a defective tumor suppressor allele. Famous examples are:

* certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer
* tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)
* Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft tissue sarcoma, brain tumors) due to mutations of p53
* Turcot syndrome (brain tumors and colonic polyposis)
* Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
* Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome) can include familial cases of colon cancer, uterine cancer, gastric cancer, and ovarian cancer, without a preponderance of colon polyps.
* Retinoblastoma, when occurring in young children, is due to a hereditary mutation in the retinoblastoma gene.
* Down syndrome patients, who have an extra chromosome 21, are known to develop malignancies such as leukemia and testicular cancer, though the reasons for this difference are not well understood.

Other causes

Excepting the rare transmissions that occur with pregnancies and only a marginal few organ donors, cancer is generally not a transmissible disease. The main reason for this is tissue graft rejection caused by MHC incompatibility.[31] In humans and other vertebrates, the immune system uses MHC antigens to differentiate between "self" and "non-self" cells because these antigens are different from person to person. When non-self antigens are encountered, the immune system reacts against the appropriate cell. Such reactions may protect against tumour cell engraftment by eliminating implanted cells. In the United States, approximately 3,500 pregnant women have a malignancy annually, and transplacental transmission of acute leukaemia, lymphoma, melanoma and carcinoma from mother to fetus has been observed.[31] The development of donor-derived tumors from organ transplants is exceedingly rare. The main cause of organ transplant associated tumors seems to be malignant melanoma, that was undetected at the time of organ harvest.[32]

A few types of cancer in non-humans have been found to be caused by transmission of the tumor cells themselves. This phenomenon is seen in dogs with Sticker's sarcoma, also known as canine transmissible venereal tumor,[33] as well as Devil facial tumour disease in Tasmanian devils.

Pathophysiology
Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.

Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, genes which regulate cell growth and differentiation must be altered.[34] Genetic changes can occur at many levels, from gain or loss of entire chromosomes to a mutation affecting a single DNA nucleotide. There are two broad categories of genes which are affected by these changes. Oncogenes may be normal genes which are expressed at inappropriately high levels, or altered genes which have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. Tumor suppressor genes are genes which inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.[35]

There is a diverse classification scheme for the various genomic changes which may contribute to the generation of cancer cells. Most of these changes are mutations, or changes in the nucleotide sequence of genomic DNA. Aneuploidy, the presence of an abnormal number of chromosomes, is one genomic change which is not a mutation, and may involve either gain or loss of one or more chromosomes through errors in mitosis.

Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.

Epigenetics

Epigenetics is the study of the regulation of gene expression through chemical, non-mutational changes in DNA structure. The theory of epigenetics in cancer pathogenesis is that non-mutational changes to DNA can lead to alterations in gene expression. Normally, oncogenes are silent, for example, because of DNA methylation. Loss of that methylation can induce the aberrant expression of oncogenes, leading to cancer pathogenesis. Known mechanisms of epigenetic change include DNA methylation, and methylation or acetylation of histone proteins bound to chromosomal DNA at specific locations. Classes of medications, known as HDAC inhibitors and DNA methyltransferase inhibitors, can re-regulate the epigenetic signaling in the cancer cell.

Oncogenes

Oncogenes promote cell growth through a variety of ways. Many can produce hormones, a "chemical messenger" between cells which encourage mitosis, the effect of which depends on the signal transduction of the receiving tissue or cells. In other words, when a hormone receptor on a recipient cell is stimulated, the signal is conducted from the surface of the cell to the cell nucleus to effect some change in gene transcription regulation at the nuclear level. Some oncogenes are part of the signal transduction system itself, or the signal receptors in cells and tissues themselves, thus controlling the sensitivity to such hormones. Oncogenes often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and enzymes responsible for producing the products and biochemicals cells use and interact with.

Mutations in proto-oncogenes, which are the normally quiescent counterparts of oncogenes, can modify their expression and function, increasing the amount or activity of the product protein. When this happens, the proto-oncogenes become oncogenes, and this transition upsets the normal balance of cell cycle regulation in the cell, making uncontrolled growth possible. The chance of cancer cannot be reduced by removing proto-oncogenes from the genome, even if this were possible, as they are critical for growth, repair and homeostasis of the organism. It is only when they become mutated that the signals for growth become excessive.

One of the first oncogenes to be defined in cancer research is the ras oncogene. Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumours.[36] Ras was originally identified in the Harvey sarcoma virus genome, and researchers were surprised that not only was this gene present in the human genome but that, when ligated to a stimulating control element, could induce cancers in cell line cultures.[37]

Tumor suppressor genes

Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally, tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of the cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. The p53 protein, one of the most important studied tumor suppressor genes, is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage.

Despite nearly half of all cancers possibly involving alterations in p53, its tumor suppressor function is poorly understood. p53 clearly has two functions: one a nuclear role as a transcription factor, and the other a cytoplasmic role in regulating the cell cycle, cell division, and apoptosis.

The Warburg hypothesis is the preferential use of glycolysis for energy to sustain cancer growth. p53 has been shown to regulate the shift from the respiratory to the glycolytic pathway.[38]

However, a mutation can damage the tumor suppressor gene itself, or the signal pathway which activates it, "switching it off". The invariable consequence of this is that DNA repair is hindered or inhibited: DNA damage accumulates without repair, inevitably leading to cancer.

Mutations of tumor suppressor genes that occur in germline cells are passed along to offspring, and increase the likelihood for cancer diagnoses in subsequent generations. Members of these families have increased incidence and decreased latency of multiple tumors. The tumor types are typical for each type of tumor suppressor gene mutation, with some mutations causing particular cancers, and other mutations causing others. The mode of inheritance of mutant tumor suppressors is that an affected member inherits a defective copy from one parent, and a normal copy from the other. For instance, individuals who inherit one mutant p53 allele (and are therefore heterozygous for mutated p53) can develop melanomas and pancreatic cancer, known as Li-Fraumeni syndrome. Other inherited tumor suppressor gene syndromes include Rb mutations, linked to retinoblastoma, and APC gene mutations, linked to adenopolyposis colon cancer. Adenopolyposis colon cancer is associated with thousands of polyps in colon while young, leading to colon cancer at a relatively early age. Finally, inherited mutations in BRCA1 and BRCA2 lead to early onset of breast cancer.

Development of cancer was proposed in 1971 to depend on at least two mutational events. In what became known as the Knudson two-hit hypothesis, an inherited, germ-line mutation in a tumor suppressor gene would only cause cancer if another mutation event occurred later in the organism's life, inactivating the other allele of that tumor suppressor gene.[39]

Usually, oncogenes are dominant, as they contain gain-of-function mutations, while mutated tumor suppressors are recessive, as they contain loss-of-function mutations. Each cell has two copies of the same gene, one from each parent, and under most cases gain of function mutations in just one copy of a particular proto-oncogene is enough to make that gene a true oncogene. On the other hand, loss of function mutations need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one mutated copy of a tumor suppressor gene can render the other, wild-type copy non-functional. This phenomenon is called the dominant negative effect and is observed in many p53 mutations.

Knudson’s two hit model has recently been challenged by several investigators. Inactivation of one allele of some tumor suppressor genes is sufficient to cause tumors. This phenomenon is called haploinsufficiency and has been demonstrated by a number of experimental approaches. Tumors caused by haploinsufficiency usually have a later age of onset when compared with those by a two hit process.[40]

Cancer cell biology
Tissue can be organized in a continuous spectrum from normal to cancer.

Often, the multiple genetic changes which result in cancer may take many years to accumulate. During this time, the biological behavior of the pre-malignant cells slowly change from the properties of normal cells to cancer-like properties. Pre-malignant tissue can have a distinctive appearance under the microscope. Among the distinguishing traits are an increased number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, and loss of normal tissue organization. Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure in pre-malignant cells. These early neoplastic changes must be distinguished from hyperplasia, a reversible increase in cell division caused by an external stimulus, such as a hormonal imbalance or chronic irritation.

The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and has not shown invasion into other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.

Clonal evolution

Main article: Somatic evolution in cancer

The process by which normal tissue becomes malignant is a process of somatic evolution within the body.[41] Millions of years of biological evolution insure that the cellular metabolic changes that enable cancer to grow occur only very rarely. Most changes in cellular metabolism that allow cells to grow in a disorderly fashion lead to cell death. Cancer cells undergo a process of natural selection, in that the few cells with new genetic changes that enhance their survival or reproduction continue to multiply, and soon come to dominate the growing tumor, as cells with less favorable genetic change are out-competed.[42] This process is called clonal evolution. Tumors often continue to evolve in response to chemotherapy treatments, and on occasion aberrant cells may acquire resistance to particular anti-cancer pharmaceuticals.

Biological properties of cancer cells

In a 2000 article by Hanahan and Weinberg, the biological properties of malignant tumor cells were summarized as follows:[43]

* Acquisition of self-sufficiency in growth signals, leading to unchecked growth.
* Loss of sensitivity to anti-growth signals, also leading to unchecked growth.
* Loss of capacity for apoptosis, in order to allow growth despite genetic errors and external anti-growth signals.
* Loss of capacity for senescence, leading to limitless replicative potential (immortality)
* Acquisition of sustained angiogenesis, allowing the tumor to grow beyond the limitations of passive nutrient diffusion.
* Acquisition of ability to invade neighbouring tissues, the defining property of invasive carcinoma.
* Acquisition of ability to build metastases at distant sites, the classical property of malignant tumors (carcinomas or others).

The completion of these multiple steps would be a very rare event without :

* Loss of capacity to repair genetic errors, leading to an increased mutation rate (genomic instability), thus accelerating all the other changes.

These biological changes are classical in carcinomas; other malignant tumor may not need all to achieve them all. For example, tissue invasion and displacement to distant sites are normal properties of leukocytes; these steps are not needed in the development of leukemia. The different steps do not necessarily represent individual mutations. For example, inactivation of a single gene, coding for the p53 protein, will cause genomic instability, evasion of apoptosis and increased angiogenesis. Not all the cancer cells are dividing. Rather, a subset of the cells in a tumor, called cancer stem cells, replicate themselves and generate differentiated cells.[44]

Prevention

Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of pre-malignant lesions). The epidemiological concept of "prevention" is usually defined as either primary prevention, for people who have not been diagnosed with a particular disease, or secondary prevention, aimed at reducing recurrence or complications of a previously diagnosed illness.

Observational epidemiological studies that show associations between risk factors and specific cancers mostly serve to generate hypotheses about potential interventions that could reduce cancer incidence or morbidity. Randomized controlled trials then test whether hypotheses generated by epidemiological trials and laboratory research actually result in reduced cancer incidence and mortality. In many cases, findings from observational epidemiological studies are not confirmed by randomized controlled trials.

About a third of the twelve most common cancers worldwide are due to nine potentially modifiable risk factors. Men with cancer are twice as likely as women to have a modifiable risk factor for their disease. The nine risk factors are tobacco smoking, excessive alcohol use, diet low in fruit and vegetables, limited physical exercise, human papillomavirus infection (unsafe sex), urban air pollution, domestic use of solid fuels, and contaminated injections (hepatitis B and C).[45]

Modifiable ("lifestyle") risk factors

The vast majority of cancer risk factors are environmental or lifestyle-related in nature, leading to the claim that cancer is a largely preventable disease.[45] Examples of modifiable cancer risk factors include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men[46]), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexually transmitted diseases (such as those conveyed by the human papillomavirus), the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, and certain occupational and chemical exposures.

Every year, at least 200,000 people die worldwide from cancer related to their workplace.[47] Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco smoke, or leukemia from exposure to benzene at their workplaces.[47] Currently, most cancer deaths caused by occupational risk factors occur in the developed world.[47] It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation.[48]

See alcohol and cancer for more on that topic.

Diet

Main article: Diet and cancer

The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States). Studies have shown that immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.[49] Whether reducing obesity in a population also reduces cancer incidence is unknown.

Despite frequent reports of particular substances (including foods) having a beneficial or detrimental effect on cancer risk, few of these have an established link to cancer. These reports are often based on studies in cultured cell media or animals. Public health recommendations cannot be made on the basis of these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.

Proposed dietary interventions for primary cancer risk reduction generally gain support from epidemiological association studies. Examples of such studies include reports that reduced meat consumption is associated with decreased risk of colon cancer,[50] and reports that consumption of coffee is associated with a reduced risk of liver cancer.[51] Studies have linked consumption of grilled meat to an increased risk of stomach cancer,[52] colon cancer,[53] breast cancer,[54] and pancreatic cancer,[55] a phenomenon which could be due to the presence of carcinogens such as benzopyrene in foods cooked at high temperatures.

A 2005 secondary prevention study showed that consumption of a plant-based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time.[56] These results were amplified by a 2006 study in which over 2,400 women were studied, half randomly assigned to a normal diet, the other half assigned to a diet containing less than 20% calories from fat. The women on the low fat diet were found to have a markedly lower risk of breast cancer recurrence, in the interim report of December, 2006.[57]

Recent studies have also demonstrated potential links between some forms of cancer and high consumption of refined sugars and other simple carbohydrates.[58][59][60][61][62] Although the degree of correlation and the degree of causality is still debated,[63][64][65] some organizations have in fact begun to recommend reducing intake of refined sugars and starches as part of their cancer prevention regimens.[66][67][68]

In November 2007, the American Institute for Cancer Research (AICR), in conjunction with the World Cancer Research Fund (WCRF), published Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective', "the most current and comprehensive analysis of the literature on diet, physical activity and cancer".[69] The WCRF/AICR Expert Report lists 10 recommendations that people can follow to help reduce their risk of developing cancer, including the following dietary guidelines: (1) reducing intake of foods and drinks that promote weight gain, namely energy-dense foods and sugary drinks, (2) eating mostly foods of plant origin, (3) limiting intake of red meat and avoiding processed meat, (4) limiting consumption of alcoholic beverages, and (5) reducing intake of salt and avoiding mouldy cereals (grains) or pulses (legumes).[70][71]

Vitamins

The idea that cancer can be prevented through vitamin supplementation stems from early observations correlating human disease with vitamin deficiency, such as pernicious anemia with vitamin B12 deficiency, and scurvy with Vitamin C deficiency. This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer. The cancer-fighting components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly being advised to consume fresh, unprocessed fruits and vegetables for maximal health benefits.[72]

Epidemiological studies have shown that low vitamin D status is correlated to increased cancer risk.[73][74] However, the results of such studies need to be treated with caution, as they cannot show whether a correlation between two factors means that one causes the other (i.e. correlation does not imply causation).[75] The possibility that Vitamin D might protect against cancer has been contrasted with the risk of malignancy from sun exposure. Since exposure to the sun enhances natural human production of vitamin D, some cancer researchers have argued that the potential deleterious malignant effects of sun exposure are far outweighed by the cancer-preventing effects of extra vitamin D synthesis in sun-exposed skin. In 2002, Dr. William B. Grant claimed that 23,800 premature cancer deaths occur in the US annually due to insufficient UVB exposure (apparently via vitamin D deficiency).[76] This is higher than 8,800 deaths occurred from melanoma or squamous cell carcinoma, so the overall effect of sun exposure might be beneficial. Another research group[77][78] estimates that 50,000–63,000 individuals in the United States and 19,000 - 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D.

The case of beta-carotene provides an example of the importance of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in lung cancer. This hypothesis led to a series of large randomized clinical trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but not significantly, increased by beta-carotene, leading to an early termination of the study.[79]

Results reported in the Journal of the American Medical Association (JAMA) in 2007 indicate that folic acid supplementation is not effective in preventing colon cancer, and folate consumers may be more likely to form colon polyps.[80]

Chemoprevention

The concept that medications could be used to prevent cancer is an attractive one, and many high-quality clinical trials support the use of such chemoprevention in defined circumstances.

Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile.[81]

Raloxifene is a SERM like tamoxifen; it has been shown (in the STAR trial) to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, raloxifene had fewer side effects than tamoxifen, though it did permit more DCIS to form.[81]

Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors.[82] The effect of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients[83] and in the general population.[84][85] In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity.

Genetic testing

Genetic testing for high-risk individuals is already available for certain cancer-related genetic mutations. Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance, chemoprevention, or risk-reducing surgery. Early identification of inherited genetic risk for cancer, along with cancer-preventing interventions such as surgery or enhanced surveillance, can be lifesaving for high-risk individuals.
Gene Cancer types Availability
BRCA1, BRCA2 Breast, ovarian, pancreatic Commercially available for clinical specimens
MLH1, MSH2, MSH6, PMS1, PMS2 Colon, uterine, small bowel, stomach, urinary tract Commercially available for clinical specimens

Vaccination

Prophylactic vaccines have been developed to prevent infection by oncogenic infectious agents such as viruses, and therapeutic vaccines are in development to stimulate an immune response against cancer-specific epitopes.[86]

As reported above, a preventive human papillomavirus vaccine exists that targets certain sexually transmitted strains of human papillomavirus that are associated with the development of cervical cancer and genital warts. The only two HPV vaccines on the market as of October 2007 are Gardasil and Cervarix.[86] There is also a hepatitis B vaccine, which prevents infection with the hepatitis B virus, an infectious agent that can cause liver cancer.[86]

Screening
It has been suggested that this section be split into a new article entitled Cancer screening. (Discuss)

Cancer screening is an attempt to detect unsuspected cancers in an asymptomatic population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.

Screening for cancer can lead to earlier diagnosis in specific cases. Early diagnosis may lead to extended life, but may also falsely prolong the lead time to death through lead time bias or length time bias.

A number of different screening tests have been developed for different malignancies. Breast cancer screening can be done by breast self-examination, though this approach was discredited by a 2005 study in over 300,000 Chinese women. Screening for breast cancer with mammograms has been shown to reduce the average stage of diagnosis of breast cancer in a population. Stage of diagnosis in a country has been shown to decrease within ten years of introduction of mammographic screening programs. Colorectal cancer can be detected through fecal occult blood testing and colonoscopy, which reduces both colon cancer incidence and mortality, presumably through the detection and removal of pre-malignant polyps. Similarly, cervical cytology testing (using the Pap smear) leads to the identification and excision of precancerous lesions. Over time, such testing has been followed by a dramatic reduction of cervical cancer incidence and mortality. Testicular self-examination is recommended for men beginning at the age of 15 years to detect testicular cancer. Prostate cancer can be screened using a digital rectal exam along with prostate specific antigen (PSA) blood testing, though some authorities (such as the US Preventive Services Task Force) recommend against routinely screening all men.

Screening for cancer is controversial in cases when it is not yet known if the test actually saves lives. The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments. For example: when screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to treatment. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation. Follow up procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). Similarly, for breast cancer, there have recently been criticisms that breast screening programs in some countries cause more problems than they solve. This is because screening of women in the general population will result in a large number of women with false positive results which require extensive follow-up investigations to exclude cancer, leading to having a high number-to-treat (or number-to-screen) to prevent or catch a single case of breast cancer early.

Cervical cancer screening via the Pap smear has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being largely caused by a virus, it has clear risk factors (sexual contact), and the natural progression of cervical cancer is that it normally spreads slowly over a number of years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.

For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake cancer screening.

Use of medical imaging to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an incidentaloma - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations. Recent studies of CT scan-based screening for lung cancer in smokers have had equivocal results, and systematic screening is not recommended as of July 2007. Randomized clinical trials of plain-film chest X-rays to screen for lung cancer in smokers have shown no benefit for this approach.

Canine cancer detection has shown promise, but is still in the early stages of research.

Epidemiology
The risk of cancer rises with age

Cancer epidemiology is the study of the incidence of cancer as a way to infer possible trends and causes. The first such cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that cancer of the scrotum was a common disease among chimney sweeps. The work of other individual physicians led to various insights, but when physicians started working together they could make firmer conclusions.

A founding paper of this discipline was the work of Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health. Her ground-breaking work on cancer epidemiology was carried on by Richard Doll and Austin Bradford Hill, who published "Lung Cancer and Other Causes of Death In Relation to Smoking. A Second Report on the Mortality of British Doctors" followed in 1956 (otherwise known as the British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large amounts of cancer data. Modern epidemiological methods are closely linked to current concepts of disease and public health policy. Over the past 50 years, great efforts have been spent on gathering data across medical practise, hospital, provincial, state, and even country boundaries, as a way to study the interdependence of environmental and cultural factors on cancer incidence.

Cancer epidemiology must contend with problems of lead time bias and length time bias. Lead time bias is the concept that early diagnosis may artificially inflate the survival statistics of a cancer, without really improving the natural history of the disease. Length bias is the concept that slower growing, more indolent tumors are more likely to be diagnosed by screening tests, but improvements in diagnosing more cases of indolent cancer may not translate into better patient outcomes after the implementation of screening programs. A similar epidemiological concern is overdiagnosis, the tendency of screening tests to diagnose diseases that may not actually impact the patient's longevity. This problem especially applies to prostate cancer and PSA screening.[87]

Some cancer researchers have argued that negative cancer clinical trials lack sufficient statistical power to discover a benefit to treatment. This may be due to fewer patients enrolled in the study than originally planned.[88]

State and regional cancer registries are organizations that abstract clinical data about cancer from patient medical records. These institutions provide information to state and national public health groups to help track trends in cancer diagnosis and treatment. One of the largest and most important cancer registries is SEER, administered by the US Federal government.[89] Health information privacy concerns have led to the restricted use of cancer registry data in the United States Department of Veterans Affairs[90][91][92] and other institutions.[93]

In some Western countries, such as the USA,[4] and the UK[94] cancer is overtaking cardiovascular disease as the leading cause of death. In many Third World countries cancer incidence (insofar as this can be measured) appears much lower, most likely because of the higher death rates due to infectious disease or injury. With the increased control over malaria and tuberculosis in some Third World countries, incidence of cancer is expected to rise; this is termed the epidemiologic transition in epidemiological terminology.

Cancer epidemiology closely mirrors risk factor spread in various countries. Hepatocellular carcinoma (liver cancer) is rare in the West but is the main cancer in China and neighbouring countries, most likely due to the endemic presence of hepatitis B and aflatoxin in that population. Similarly, with tobacco smoking becoming more common in various Third World countries, lung cancer incidence has increased in a parallel fashion.

History
Typical macroscopic appearance of cancer. This invasive ductal carcinoma of the breast (pale area at the center) shows an oval tumor surrounded by spikes of whitish scar tissue in the surrounding yellow fatty tissue. The silhouette vaguely resembles a crab.

Today, the Greek term carcinoma is the medical term for a malignant tumor derived from epithelial cells. It is Celsus who translated carcinos into the Latin cancer, also meaning crab. Galen used "oncos" to describe all tumours, the root for the modern word oncology.[95]

Hippocrates described several kinds of cancers. He called benign tumours oncos, Greek for swelling, and malignant tumours carcinos, Greek for crab or crayfish. This name comes from the appearance of the cut surface of a solid malignant tumour, with the veins stretched on all sides as the animal the crab has its feet, whence it derives its name[96] (see picture). He later added the suffix -oma, Greek for swelling, giving the name carcinoma. Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatment was based on the humor theory of four bodily fluids (black and yellow bile, blood, and phlegm). According to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remained popular until the 19th century with the discovery of cells.

Our oldest description and surgical treatment of cancer was discovered in Egypt and dates back to approximately 1600 B.C. The Papyrus describes 8 cases of ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."[97]

Another very early surgical treatment for cancer was described in the 1020s by Avicenna (Ibn Sina) in The Canon of Medicine. He stated that the excision should be radical and that all diseased tissue should be removed, which included the use of amputation or the removal of veins running in the direction of the tumor. He also recommended the use of cauterization for the area being treated if necessary.[98]

In the 16th and 17th centuries, it became more acceptable for doctors to dissect bodies to discover the cause of death. The German professor Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor Francois de la Boe Sylvius, a follower of Descartes, believed that all disease was the outcome of chemical processes, and that acidic lymph fluid was the cause of cancer. His contemporary Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was contagious.[99]

With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("metastasis"). This view of the disease was first formulated by the English surgeon Campbell De Morgan between 1871 and 1874.[100] The use of surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, asepsis improved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late 1800s felt that the rate of cure after surgery had been higher before asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor. During the same period, the idea that the body was made up of various tissues, that in turn were made up of millions of cells, laid rest the humor-theories about chemical imbalances in the body. The age of cellular pathology was born.

When Marie Curie and Pierre Curie discovered radiation at the end of the 19th century, they stumbled upon the first effective non-surgical cancer treatment. With radiation came also the first signs of multi-disciplinary approaches to cancer treatment. The surgeon was no longer operating in isolation, but worked together with hospital radiologists to help patients. The complications in communication this brought, along with the necessity of the patient's treatment in a hospital facility rather than at home, also created a parallel process of compiling patient data into hospital files, which in turn led to the first statistical patient studies.

Cancer patient treatment and studies were restricted to individual physicians' practices until World War II, when medical research centers discovered that there were large international differences in disease incidence. This insight drove national public health bodies to make it possible to compile health data across practises and hospitals, a process that many countries do today. The Japanese medical community observed that the bone marrow of bomb victims in Hiroshima and Nagasaki was completely destroyed. They concluded that diseased bone marrow could also be destroyed with radiation, and this led to the discovery of bone marrow transplants for leukemia. Since WWII, trends in cancer treatment are to improve on a micro-level the existing treatment methods, standardize them, and globalize them as a way to find cures through epidemiology and international partnerships.

Research

Main article: Cancer research

Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. The improved understanding of molecular biology and cellular biology due to cancer research has led to a number of new, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971. Since 1971 the United States has invested over $200 billion on cancer research, that total includes money invested by public and private sectors and foundations

Pharmacology

2009-01-23T11:54:00.001-08:00

Pharmacology (from Greek φάρμακον, pharmakon, "drug"; and -λογία, -logia) is the study of drug action.[1] More specifically it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties, interactions, toxicology, therapy, and medical applications and antipathogenic capabilities. Pharmacology is not synonymous with pharmacy, which is the name used for a profession, though in common usage the two terms are confused at times. Pharmacology deals with how drugs interact within biological systems to affect function. It is the study of drugs, of the body's reaction to drugs, the sources of drugs, their nature, and their properties. In contrast, pharmacy is a medical science concerned with the safe and effective use of medicines.
The origins of clinical pharmacology date back to the Middle Ages in Avicenna's The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas.[2] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.[3] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.[4] The first pharmacology department was set up by Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.[3]
Early pharmacologists focused on natural substances, mainly plant extracts. Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.[5]
Contents
[hide]
• 1 Divisions
• 2 Scientific background
• 3 Medicine development and safety testing
• 4 Drug legislation and safety
• 5 Education
• 6 See also
• 7 Footnotes
• 8 External links

[edit] Divisions
Pharmacology as a chemical science is practiced by pharmacologists. Subdisciplines include
• clinical pharmacology - the medical field of medication effects on humans
• neuro- and psychopharmacology (effects of medication on behavior and nervous system functioning),
• pharmacogenetics (clinical testing of genetic variation that gives rise to differing response to drugs)
• pharmacogenomics (application of genomic technologies to new drug discovery and further characterization of older drugs)
• pharmacoepidemiology (study of effects of drugs in large numbers of people)
• toxicology study of harmful effects of drugs
• theoretical pharmacology
• posology - how medicines are dosed
• pharmacognosy - deriving medicines from plants
[edit] Scientific background
The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function).
A chemical has, from the pharmacological point-of-view, various properties. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic).
When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in LADME:
• Liberation - disintegration (for solid oral forms {breaking down into smaller particles}), dispersal and dissolution
• Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)?
• Distribution - How does it spread through the organism?
• Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic?
• Excretion - How is the medication eliminated (through the bile, urine, breath, skin)?
Medication is said to have a narrow or wide therapeutic index or therapeutic window. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors.
[edit] Medicine development and safety testing
Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration and they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMEA and they enforce standards set by the European Pharmacopoeia.
If the chemical structure of a medicinal compound is altered slightly, this could slightly or dramatically alter the medicinal properties of the compound depending on the level of alteration as it relates to the structural composition of the substrate or receptorsite on which it exerts its medicinal effect, a concept referred to as the structural activity relationship (SAR) . This means when a useful activity has been identified, chemists will make many similar compounds called analogues, in an attempt to maximize the desired medicinal effect(s) of the compound. This development phase can take anywhere from a few years to a decade or more and is very expensive.[6]
These new analogues need to be developed. It needs to be determined how safe the medicine is for human consumption, its stability in the human body and the best form for delivery to the desired organ system, like tablet or aerosol. After extensive testing, which can take up to 6 years the new medicine is ready for marketing and selling.[6]
As a result of the long time required to develop analogues and test a new medicine and the fact that of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, costing millions of dollars. To recoup this outlay pharmaceutical companies may do a number of things:[6]
• Carefully research the demand for their potential new product before spending an outlay of company funds.[6]
• Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time.[6]
[edit] Drug legislation and safety
In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements:
1. The drug must be found to be effective against the disease for which it is seeking approval.
2. The drug must meet safety criteria by being subject to extensive animal and controlled human testing.
Gaining FDA approval usually takes several years to attain. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome.[7]
The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987.
The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.
[edit] Education
The study of pharmacology is offered in many universities worldwide.
Again, pharmacology education programs differ from pharmacy programs. Students of pharmacology are trained as researchers, studying the effects of substances in order to better understand the mechanisms which might lead to new drug discoveries for example. Whereas a pharmacy student will eventually work in a pharmacy dispensing medications or some other position focused on the patient, pharmacologist will typically work within a laboratory setting.
Some higher educational institutions combine pharmacology and toxicology into a single program as does Michigan State University. Michigan State University offers PhD training in Pharmacology & Toxicology with an optional Environmental Toxicology specialization. They also offer a Professional Science Masters in Integrative Pharmacology.

PHARMACOLGY

2009-01-23T11:49:00.000-08:00

Obesity

2009-01-22T11:44:00.000-08:00

What is obesity?
The definition of obesity varies depending on what one reads, but in general, it is a chronic condition defined by an excess amount body fat. A certain amount of body fat is necessary for storing energy, heat insulation, shock absorption, and other functions. The normal amount of body fat (expressed as percentage of body fat) is between 25%-30% in women and 18%-23% in men. Women with over 30% body fat and men with over 25% body fat are considered obese.
The calculation of body mass index (BMI) has also been used in the definition of obesity. The body mass index (BMI) equals a person's weight in kilograms (kg) divided by their height in meters (m) squared. Since BMI describes body weight relative to height, it is strongly correlated with total body fat content in adults. "Obesity" is defined as a BMI of 30 and above.
How common is obesity?
Obesity has reached epidemic proportions in the United States. One in three Americans is obese. The prevalence of obesity in children has increased markedly, with approximately 20%-25 % of children either overweight or obese. Obesity is also increasing rapidly throughout the world, and the incidence of obesity nearly doubled form 1991 to 1998.
Being Overweight Doesn't Mean You're Unhealthy!
Medical Author: Benjamin C. Wedro, MD, FAAEM
Medical Editor: Melissa Conrad Stöppler, MD
The results of a study published in the Archives of Internal Medicine should not come as a shock to most people. Being overweight doesn't necessarily make you unhealthy, according to researchers in both the United States and Germany. Sports fans have known this forever; elite athletes can have an appearance ranging from tiny Olympic gymnasts to massive NFL linemen. Athletes at both extremes- and all those in between- are in shape and trained to perform at high levels.
The new research confirmed this. People who are overweight have a fifty-fifty chance of having high cholesterol, high blood pressure, or elevated blood sugar levels. Pretty good odds, but not as good as those for people who are within the normal weight range. They have a 75% chance of having normal results on blood tests for cholesterol and blood sugar. And for those who are obese, the chance of having normal results falls to one-third.
The definition of "ideal body weight" has been a thorn in the side of many people. Perceptions of how people appear, how their clothes fit, and how fat they are have permitted whole industries to flourish. Weight loss clinics, gyms and fitness centers, liposuction, and gastric bypass surgeries all were based at least partly on the presumption that being overweight equaled being at risk for heart disease and diabetes. The studies in the Archives of Internal Medicine found that there may be more to health than meets the eye.
Read more about obesity and disease risk »
Top Obesity Terms
diseases, causes, childhood, statistics, teens, definition, morbid, fast food, overweight, BMI
What are the health risks associated with obesity?
Obesity is not just a cosmetic consideration; it is a dire health dilemma directly harmful to one's health. In the United States, roughly 300,000 deaths per year are directly related to obesity, and more than 80% of these deaths are in patients with a BMI (body mass index, which will be discussed later in this article) over 30. For patients with a BMI over 40, life expectancy is reduces significantly (as much as 20 years for men and 5 years for women ). Obesity also increases the risk of developing a number of chronic diseases including:
• Insulin Resistance. Insulin is necessary for the transport of blood glucose (sugar) into the cells of muscle and fat (which is then used for energy). By transporting glucose into cells, insulin keeps the blood glucose levels in the normal range. Insulin resistance (IR) is the condition whereby the effectiveness of insulin in transporting glucose (sugar) into cells is diminished. Fat cells are more insulin resistant than muscle cells; therefore, one important cause of insulin resistance is obesity. The pancreas initially responds to insulin resistance by producing more insulin. As long as the pancreas can produce enough insulin to overcome this resistance, blood glucose levels remain normal. This insulin resistance state (characterized by normal blood glucose levels and high insulin levels) can last for years. Once the pancreas can no longer keep up with producing high levels of insulin, blood glucose levels begin to rise, resulting in type 2 diabetes, thus insulin resistance is a pre-diabetes condition. In fact scientists now believe that the atherosclerosis (hardening of the arteries) associated with diabetes likely develops during this insulin resistance period.
• Type 2 (adult-onset) diabetes. The risk of type 2 diabetes increases with the degree and duration of obesity. Type 2 diabetes is associated with central obesity; a person with central obesity has excess fat around his/her waist, so that the body is shaped like an apple.
• High blood pressure (hypertension). Hypertension is common among obese adults. A Norwegian study showed that weight gain tended to increase blood pressure in women more significantly than in men. The risk of developing high blood pressure is also higher in obese people who are apple shaped (central obesity) than in people who are pear shaped (fat distribution mainly in hips and thighs).
• High cholesterol (hypercholesterolemia)
• Stroke (cerebrovascular accident or CVA)
• Heart attack. A prospective study found that the risk of developing coronary artery disease increased three to four times in women who had a BMI greater than 29. A Finnish study showed that for every one kilogram (2.2 pounds) increase in body weight, the risk of death from coronary artery disease increased by one percent. In patients who have already had a heart attack, obesity is associated with an increased likelihood of a second heart attack.
• Congestive heart failure
• Cancer. While not conclusively proven, some observational studies have linked obesity to cancer of the colon in men and women, cancer of the rectum and prostate in men, and cancer of the gallbladder and uterus in women. Obesity may also be associated with breast cancer, particularly in postmenopausal women. Fat tissue is important in the production of estrogen, and prolonged exposure to high levels of estrogen increases the risk of breast cancer.
What Causes Obesity?
The balance between calorie intake and energy expenditure determines a person's weight. If a person eats more calories than he or she burns (metabolizes), the person gains weight (the body will store the excess energy as fat). If a person eats fewer calories than he or she metabolizes, he or she will lose weight. Therefore the most common causes of obesity are overeating and physical inactivity. At present, we know that there are many factors that contribute to obesity, some of which have a genetic component:
• Genetics. A person is more likely to develop obesity if one or both parents are obese. Genetics also affect hormones involved in fat regulation. For example, one genetic cause of obesity is leptin deficiency. Leptin is a hormone produced in fat cells, and also in the placenta. Leptin controls weight by signaling the brain to eat less when body fat stores are too high. If, for some reason the body cannot produce enough leptin, or leptin cannot signal the brain to eat less, this control is lost, and obesity occurs. The role of leptin replacement as a treatment for obesity is currently being explored.
• Overeating. Overeating leads to weight gain, especially if the diet is high in fat. Foods high in fat or sugar (for example, fast food, fried food, and sweets) have high energy density (foods that have a lot of calories in a small amount of food). Epidemiologic studies have shown that diets high in fat contribute to weight gain.
• A diet high in simple carbohydrates. The role of carbohydrates in weight gain is not clear. Carbohydrates increase blood glucose levels, which in turn stimulate insulin release by the pancreas, and insulin promotes the growth of fat tissue and can cause weight gain. Some scientists believe that simple carbohydrates (sugars, fructose, desserts, soft drinks, beer, wine, etc.) contribute to weight gain because they are more rapidly absorbed into the blood-stream than complex carbohydrates (pasta, brown rice, grains, vegetables, raw fruits, etc.) and thus cause a more pronounced insulin release after meals than complex carbohydrates. This higher insulin release, some scientists believe, contributes to weight gain.
• Frequency of eating. The relationship between frequency of eating (how often you eat) and weight is somewhat controversial. There are many reports of overweight people eating less often than people with normal weight. Scientists have observed that people who eat small meals four or five times daily, have lower cholesterol levels and lower and/or more stable blood sugar levels than people who eat less frequently (two or three large meals daily). One possible explanation is that small frequent meals produce stable insulin levels, whereas large meals cause large spikes of insulin after meals.
• Slow metabolism. Women have less muscle than men. Muscle burns (metabolizes) more calories than other tissue (which includes fat). As a result, women have a slower metabolism than men, and hence, have a tendency to put on more weight than men, and weight loss is more difficult for women. As we age, we tend to lose muscle and our metabolism slows; therefore, we tend to gain weight as we get older particularly if we do not reduce our daily caloric intake.
• Physical inactivity. Sedentary people burn fewer calories than people who are active. The National Health and Nutrition Examination Survey (NHANES) showed that physical inactivity was strongly correlated with weight gain in both sexes.
• Medications. Medications associated with weight gain include certain antidepressants (medications used in treating depression), anti-convulsants [medications used in controlling seizures such as carbamazepine (Tegretol, Tegretol XR , Equetro, Carbatrol) and valproate], diabetes medications (medications used in lowering blood sugar such as insulin, sulfonylureas and thiazolidinediones), certain hormones such as oral contraceptives and most corticosteroids such as Prednisone. Weight gain may also be seen with some high blood pressure medications and antihistamines.
• Psychological factors. For some people, emotions influence eating habits. Many people eat excessively in response to emotions such as boredom, sadness, stress or anger. While most overweight people have no more psychological disturbances than normal weight people, about 30 percent of the people who seek treatment for serious weight problems have difficulties with binge eating.
• Diseases such as hypothyroidism, insulin resistance, polycystic ovary syndrome and Cushing's syndrome, are also contributors to obesity.
What are other factors associated with obesity?
• Ethnicity. Ethnicity factors may influence the age of onset and the rapidity of weight gain. African American women and Hispanic women tend to experience weight gain earlier in life than Caucasians and Asians. Hispanic men tend to develop obesity earlier than African American and Caucasian men.
• Childhood weight. A person's weight during childhood, the teenage years, and early adulthood may also influence the development of adult obesity. For example:
o Being mildly overweight in the early 20's was linked to a substantial incidence of obesity by age 35.
o Being overweight during older childhood is highly predictive of adult obesity, especially if a parent is also obese.
o Being overweight during the teenage years is even a greater predictor of adult obesity.
• Hormones. Women tend to gain weight especially during certain events such as pregnancy, menopause, and in some cases with the use of oral contraceptives. However, with the availability of the newer low dose estrogen pills, weight gain has not been as great a risk.
How is body fat measured?
Measuring a person's body fat percentage is not easy, and is often inaccurate if the methods are not monitored carefully. The following methods require special equipment, trained personnel, can be costly, and some are only available in certain research facilities:
• Underwater weighing (hydrostatic weighing): This method weighs a person underwater and then calculates lean body mass (muscle) and body fat. This method is one of the most accurate ones; however, it is generally done in special research facilities, and the equipment is costly.
• BOD POD: The BOD POD is a computerized, egg-shaped chamber. Using the same whole-body measurement principle as hydrostatic weighing, the BOD POD measures a subject's mass and volume, from which their whole-body density is determined. Using this data, body fat and lean muscle mass can then be calculated.
• DEXA: Dual-energy X-ray absorptiometry (DEXA) is used to measure bone density. It uses X-rays to determine not only the percentage of body fat, but also where, and how much fat is located in the body.
The following two methods are simple and straightforward:
• Skin calipers: This method measures the skinfold thickness of the layer of fat just under the skin in several parts of the body with calipers (a metal tool similar to forceps); the results are then used to calculate the percentage of body fat.
• Bioelectric impedance analysis (BIA): This is another seemingly simple method. There are two methods of the BIA. One involves standing on a special scale with footpads. A harmless amount of electrical current is sent through the body, and then percentage of body fat is calculated. The other type of BIA, involves electrodes that are typically placed on a wrist and an ankle, and on the back of the right hand and on the top of the foot. The change in voltage between the electrodes is measured. The person's body fat percentage is then calculated from the results of the BIA.
Health clubs and weight loss centers often use the skin caliper or bioelectric impedance analysis method; however, these can yield inaccurate results if an inexperienced person performs them or they are used on someone with significant obesity.
What is the role of medication in the treatment of obesity?
Medication treatment of obesity should be used only in patients who have health risks related to obesity. Medications should be used in patients with a BMI greater than 30 or in those with a BMI of greater than 27 who have other medical conditions (such as high blood pressure, diabetes, high blood cholesterol) that put them at risk for developing heart disease. Medications should not be used for cosmetic reasons.
Like diet and exercise, the goal of medication treatment has to be realistic. With successful medication treatment, one can expect an initial weight loss of at least 5 pounds during the first month of treatment, and a total weight loss of 10%-15% of the initial body weight. It is also important to remember that these medications only work when they are taken. When they are discontinued, weight gain can occur.
The first class (category) of medication used for weight control cause symptoms that mimic the sympathetic nervous system. They cause the body to feel "under stress" or " nervous." As a result, the major side effect of this class of medication is high blood pressure. This class of medication includes sibutramine (Meridia) and phentermine (Fastin, Adipex P). These medications also decrease appetite and create a sensation of fullness. Hunger and fullness (satiety) are regulated by brain chemicals called neurotransmitters. Examples of neurotransmitters include serotonin, norepinephrine, and dopamine. Anti-obesity medications that suppress appetite do so by increasing the level of these neurotransmitters at the junction (called synapse) between nerve endings in the brain.
Phentermine
Phentermine (Fastin, Adipex P) - (the other half of fen/phen) suppresses appetite by causing a release of norepinephrine by the cells. Phentermine alone is still available for treatment of obesity, but only on a short-term basis (a few weeks). The common side effects of phentermine include headache, insomnia, irritability and nervousness. Fenfluramine (the fen of fen/phen) and dexfenfluramine (Redux) suppress appetite mainly by increasing release of serotonin by the cells. Both fenfluramine and dexfenfluramine were withdrawn from the market in September 1997 because of association of these two medications with pulmonary hypertension (a rare but serious disease of the arteries in the lungs), and association of fen/phen with damage to the heart valves. Since the withdrawal of fenfluramine, some have suggested combining phentermine with fluoxetine (Prozac) - a combination that has been referred to as phen/pro. However, no clinical trials have been conducted to confirm the safety and effectiveness of this combination. Therefore, this combination is not an accepted treatment for obesity.
Sibutramine (Meridia)
Sibutramine (Meridia) suppresses appetite by increasing the amount of neurotransmitters serotonin and norepinephrine in the brain synapses. Unlike fenfluramine and dexfenfluramine, sibutramine does not increase release of these neurotransmitters from the cells. Instead, sibutramine inhibits the re-uptake of these neurotransmitters by the nerve cells. Therefore, the action of sibutramine is similar to that of anti-depressants that inhibit re-uptake of serotonin such as fluoxetine (Prozac), a medication that has been used for years without known association with pulmonary hypertension or heart valve damage.
In December 1997, the United States Food and Drug Administration (FDA) approved sibutramine (Meridia) to treat obesity (both in attaining and in maintaining weight loss). According to FDA guidelines, Meridia should be considered only for patients with a BMI of 30 or higher, or for those with a BMI of 27 or higher who also have other conditions (such as high blood pressure, diabetes mellitus, sleep apnea) that can improve with weight loss. Meridia should be accompanied by regular exercise and a reduced-calorie diet.
Meridia is available in 5, 10, and 15mg capsules. The recommended starting dose is one 10 mg capsule per day. The dose of Meridia can be increased if weight loss is inadequate. Meridia should always be prescribed by doctors familiar with the patients' medical condition, and familiar with the use and side effects of the medicine.
In clinical trials involving 6,000 individuals, Meridia produced statistically significantly more weight loss when compared to placebo (sugar pill). Generally, weight loss achieved with Meridia is modest. On average, patients treated with Meridia lost 5% to 10% of initial weight at various dosage levels. In two 12-month studies, maximal weight loss was achieved by six months, and statistically significant weight loss was maintained over 12 months.
Thus far, there are no reported increases in pulmonary hypertension or heart valve damage associated with the use of Meridia. Like any medication, however, close monitoring will be necessary to determine the drug's long-term safety and effectiveness. Certain side effects may not become apparent until months to years after release.
The known side effects of Meridia are mild and transient. They include dry mouth, headache, constipation, and insomnia. Meridia also causes a small increase in average blood pressure and heart rate. But in some individuals, the increase in blood pressure can be more pronounced. Therefore, patients on Meridia should have regular monitoring of their blood pressure. Meridia should not be used in patients with uncontrolled high blood pressure, history of stroke, coronary heart disease, and congestive heart failure.
Orlistat (Xenical, alli)
The next class (category) of drugs changes the metabolism of fat. Orlistat (Xenical, alli) is the only drug of this category that is U.S. FDA approved. This is a class of anti-obesity drugs called lipase inhibitors, or fat blockers. Fat from food can only be absorbed into the body after being broken up (a process called digestion) by digestive enzymes called lipases in the intestines. By inhibiting the action of lipase enzymes, orlistat prevents the intestinal absorption of fat by 30%. Drugs in this class do not affect brain chemistry. Theoretically, orlistat also should have minimal or no systemic side effects (side effects in other parts of the body) because the major locale of action is inside the gut lumen and very little of the drug is absorbed.
The U.S. Food and Drug Administration approved orlistat capsules, branded as alli, as an over-the-counter (OTC) treatment for overweight adults in February 2007. The drug had previously been approved in 1999 as a prescription weight loss aid, whose brand name is Xenical). The OTC preparation has a lower dosage than prescription Xenical.
Orlistat is recommended only for people 18 years of age and over in combination with a diet and exercise regimen. People who have difficulties with the absorption of food or who are not overweight should not take orlistat. Overweight is defined by the U.S. National Institutes of Health as having a body mass index (BMI) of 27 or greater.
Orlistat can be taken up to three times a day, with each fat-containing meal. The drug may be taken during the meal or up to one hour after the meal. If the meal is missed or is very low in fat content, the medications should not be taken.
The most common side effects of orlistat are changes in bowel habits. These include gas, the urgent need to have a bowel movement, oily bowel movements, oily discharge or spotting with bowel movements, an increased frequency of bowel movements, and the inability to control bowel movements. Women may also notice irregularities in the menstrual cycle while taking orlistat. Side effects are most common in the first few weeks after beginning to take orlistat. In some people the side effects persist for as long as they are taking the drug.
People with diabetes, thyroid conditions, who have received an organ transplant, or who are taking prescription medications that affect blood clotting should check with their physician before using OTC orlistat (alli), since drug interactions with certain medications are possible.
A long-term decrease in fat absorption can cause deficiency of fat-soluble vitamins (such as vitamins A, D, E, K). Therefore, patients on orlistat should receive adequate vitamin supplementation.

Diet and Weight Loss Tips

2009-01-22T11:33:00.000-08:00

Weight Loss Information and Tips for Getting Started
Calories per Hour offers the following tips to help you lose weight to look better, feel better, and live a healthier life. These tips are short and sweet and are intended as a starting point or quick reference for individuals seeking to lose weight by using the resources offered on Calories per Hour. Read the related tutorial topics to learn more about the topics discussed in these weight loss tips
1. How Did I Get Here?
Do you simply need help learning how to eat better? Probably. But if you eat poorly as a result of emotional, mental, or spiritual problems, they may have to be addressed before you can make any real progress with weight loss.
Even people who don't feel they have an eating disorder often turn to food for comfort. To learn to eat well and exercise regularly, you may also have to learn to handle the problems life throws at you without turning away from healthy eating and exercise.
Be particularly careful about all-or-nothing thinking. A common tendency when failing to stay on a diet is to abandon it altogether. Instead, try to learn from your mistakes and do better in the future.
2. Are You Ready to Diet? Again?
Diets entice us with promises of quick weight loss. But focusing on quick weight loss can lead to unhealthy eating and only short term success.
While most diets produce quick weight loss at the outset, they often cause your metabolism to slow. The result is that you have to eat less and less to keep losing weight. You quickly become discouraged, give up, and start eating like you used to. But now, with a slower metabolism, you regain all the weight you lost, and more.
Focus instead on improving your health, and you will become slim and healthy.
3. Take Control of What You Eat
There are few things that we have complete control over, but what we put in our mouths is one of them. We don't have to lose control in a restaurant or a friend's home, and we don't have to eat everything that's put in front of us.
Consider this: We love fat because it carries flavor, and restaurants aren't as interested in whether we'll be around in 30 years as whether we'll be back next week. And what about our friends?
4. Eat Frequently, and Eat Slowly
It is important to understand what happens when you skip a meal or go on a crash diet. When you skip a meal your metabolism slows to conserve your energy. And when you lose weight too quickly for a few days, your body thinks it is threatened with starvation and goes into survival mode. It fights to conserve your fat stores, and any weight loss comes mostly from water and muscle.
Never skip a meal, especially breakfast, and eat healthy snacks between meals. Eating frequently prevents hunger pangs and the binges that follow, provides consistent energy, and may be the single most effective way to maintain metabolism efficiency.
Eating slowly gives our bodies time to tell us they are full before we've eaten more than we need.
5. Eat More Fruits, Vegetables and Whole Grains
People who eat healthy, mostly unprocessed foods, including fruit, vegetables, whole grains, legumes, and limited amounts of lean animal protein, often find that they can eat as much as they want without gaining weight. If they are switching from a diet containing lots of processed foods, they find that they can eat more yet consume fewer calories -- and they lose weight.
Historically, the Chinese ate mostly rice and vegetables with a little lean meat for protein and flavor, nothing like the American Chinese restaurant dishes of deep fried sweet and sour pork. A step back to more natural foods would improve our health and waistlines.
6. Eat More Fiber
Fiber makes us feel full sooner and stays in our stomach longer than other substances we eat, slowing down our rate of digestion and keeping us feeling full longer. Due to its greater fiber content, a single serving of whole grain bread can be more filling than two servings of white bread. Fiber also moves fat through our digestive system faster so that less of it is absorbed.
Refined grains like white rice and those used to make white bread and sugary breakfast cereals have had most of their fiber and nutrients stripped away. They turn into blood sugar (glucose) so fast that, like sugar itself, they can cause a spike in our insulin level. This tells our body that plenty of energy is readily available and that it should stop burning fat and start storing it.
Eating foods with plenty of fiber will help keep our blood sugar at a more consistent level.
7. Cut Down on Sugar
Be careful about sugar in coffee and soda pop. It can add up quickly, and these drinks aren't filling.
Watch for "hidden" sugar in processed foods like bread, ketchup, salad dressing, canned fruit, applesauce, peanut butter, and soups. And be careful with "fat-free" products. Sugar is often used to replace the flavor that is lost when the fat is removed. Fat-free does not mean calorie-free.
The greater concern with the insulin spike (above) is not that it tells our body to start storing fat. Whatever we eat and don't burn up eventually gets turned into fat anyway.
The greater concern is that the insulin spike is followed by a drop in insulin level that leaves us feeling tired and hungry and wanting to eat more. The unfortunate result of this scenario is that it makes us want to eat something else with a high sugar content. When we do, we start the cycle all over again.
Regulating your blood sugar level is the most effective way to maintain your fat-burning capacity.
8. Too Much of a Bad Thing
Foods like cheese stand out as among the most fat-laden, with a great number of calories coming from fat. But as important as it is to select the healthiest foods, it is also important to consider how they are prepared.
Fried foods, especially deep-fried, contain a great amount of fat. While chicken and fish are usually leaner than beef or pork, they can contain more fat when they are fried. Look at how the number of grams of fat in a chicken breast changes depending on how it is cooked:
Cooking Method Fat
Meat Only, Roasted 3.1
Meat Only, Fried 4.1
Meat and Skin, Batter Fried 18.5
"Fried food? All I eat is salad and I still can't lose weight!"
Be careful with salad dressings, mayonnaise, and other condiments that are high in fat content. They greatly increase the calorie count and can negate the healthy aspects of a meal. Replace mayonnaise-based condiments with fat-free alternatives like fat-free yogurt, mustard, ketchup and barbecue sauce.
And remember, a gram of fat contains more than twice as many calories as a gram of protein or carbohydrate.
9. Too Little of a Good Thing
But don't try to eliminate fat altogether, as dietary fat is necessary to maintain a healthy body. It is a vital component for building body tissue and cells, and it aids in the absorption of some vitamins and other nutrients. Many people eat too much of the bad fats, but also eat too little of the good fats required for optimal health.
10. Exercise Regularly
People who exercise regularly not only lose weight faster, they are more successful at keeping it off. Exercise makes it possible to create a calorie deficit and lose weight without starving your body and slowing your metabolism.
At home, at the gym, or playing sports, participate in both aerobic and strength building activities on a regular basis. Not only does the exercise itself burn calories, but your body will continue to burn calories at a higher rate even after you're done exercising.
If walking is all you can do, then walk because it's great for you. But muscle burns more calories than fat, so put on a little muscle if you can and you will burn more calories just sitting there... looking good.
But don't sit too long. The human body is good at adapting. If you dig ditches without gloves, you will develop calluses to protect your hands. If you sit too long, you will develop extra padding to keep you comfortable!
11. Take It Easy
Unless you are excited to be following a very specific diet and exercise plan, do not try and change too much too fast. If you have been eating poorly and not exercising, both your body and your mind will have a lot of adjusting to do.
All the sugar and fat were actually quite enjoyable, and sitting on the couch didn't feel too bad, either. If you try and change everything too quickly the odds are greater that you will feel bad, get discouraged, and give up. So be patient.
A time will come when a healthy snack will taste as good as the junk food you felt bad about eating, and you will look forward to your regular exercise.
12. Begin Now
You can achieve your goals, but it won't likely happen as a result of the next fad diet. Or the one after that.
Learning to eat well and exercise is the only solution to long term weight loss.

Tobacco Facts

2009-01-21T11:26:00.000-08:00

http://www.tobaccofacts.org/pdf/posterchild.pdf

Why do some people become addicted, while others do not?

2009-01-19T06:33:00.000-08:00

No single factor can predict whether or not a person will become addicted to drugs. Risk for addiction is influenced by a person's biology, social environment, and age or stage of development. The more risk factors an individual has, the greater the chance that taking drugs can lead to addiction. For example:
• Biology. The genes that people are born with—in combination with environmental influences—account for about half of their addiction vulnerability. Additionally, gender, ethnicity, and the presence of other mental disorders may influence risk for drug abuse and addiction.

• Environment. A person's environment includes many different influences—from family and friends to socioeconomic status and quality of life in general. Factors such as peer pressure, physical and sexual abuse ,stress and parental involvement can greatly influence the course of drug abuse and addiction in a person's life.

• Development. Genetic and environmental factors interact with critical developmental stages in a person's life to affect addiction vulnerability, and adolescents experience a double challenge. Although taking drugs at any age can lead to addiction, the earlier that drug use begins, the more likely it is to progress to more serious abuse. And because adolescents' brains are still developing in the areas that govern decisionmaking, judgment, and self-control, they are especially prone to risk-taking behaviors, including trying drugs of abuse.
Prevention is the key
Drug addiction is a preventable disease. Results from NIDA-funded research have shown that prevention programs that involve the family, schools, communities, and the media are effective in reducing drug abuse. Although many events and cultural factors affect drug abuse trends, when youths perceive drug abuse as harmful, they reduce their drug taking. It is necessary, therefore, to help youth and the general public to understand the risks of drug abuse and for teachers, parents, and healthcare professionals to keep sending the message that drug addiction can be prevented if a person never abuses drugs.

What happens to your brain when you take drugs ?

2009-01-19T06:27:00.000-08:00

Drugs are chemicals that tap into the brain's communication system and disrupt the way nerve cells normally send, receive, and process information. There are at least two ways that drugs are able to do this: (1) by imitating the brain's natural chemical messengers, and/or (2) by overstimulating the "reward circuit" of the brain.
Some drugs, such as marijuana and heroin, have a similar structure to chemical messengers, called neurotransmitters, which are naturally produced by the brain. Because of this similarity, these drugs are able to "fool" the brain's receptors and activate nerve cells to send abnormal messages.
Other drugs, such as cocaine or methamphetamine, can cause the nerve cells to release abnormally large amounts of natural neurotransmitters, or prevent the normal recycling of these brain chemicals, which is needed to shut off the signal between neurons. This disruption produces a greatly amplified message that ultimately disrupts normal communication patterns.
Nearly all drugs, directly or indirectly, target the brain's reward system by flooding the circuit with dopamine. Dopamine is a neurotransmitter present in regions of the brain that control movement, emotion, motivation, and feelings of pleasure. The overstimulation of this system, which normally responds to natural behaviors that are linked to survival (eating, spending time with loved ones, etc), produces euphoric effects in response to the drugs. This reaction sets in motion a pattern that "teaches" people to repeat the behavior of abusing drugs.
As a person continues to abuse drugs, the brain adapts to the overwhelming surges in dopamine by producing less dopamine or by reducing the number of dopamine receptors in the reward circuit. As a result, dopamine's impact on the reward circuit is lessened, reducing the abuser's ability to enjoy the drugs and the things that previously brought pleasure. This decrease compels those addicted to drugs to keep abusing drugs in order to attempt to bring their dopamine function back to normal. And, they may now require larger amounts of the drug than they first did to achieve the dopamine high—an effect known as tolerance.
Long-term abuse causes changes in other brain chemical systems and circuits as well. Glutamate is a neurotransmitter that influences the reward circuit and the ability to learn. When the optimal concentration of glutamate is altered by drug abuse, the brain attempts to compensate, which can impair cognitive function. Drugs of abuse facilitate nonconscious (conditioned) learning, which leads the user to experience uncontrollable cravings when they see a place or person they associate with the drug experience, even when the drug itself is not available. Brain imaging studies of drug-addicted individuals show changes in areas of the brain that are critical to judgment, decisionmaking, learning and memory, and behavior control. Together, these changes can drive an abuser to seek out and take drugs compulsively despite adverse consequences—in other words, to become addicted to drugs

Drug Abuse and Addiction

2009-01-19T06:02:00.000-08:00

Many people do not understand why individuals become addicted to drugs or how drugs change the brain to foster compulsive drug abuse. They mistakenly view drug abuse and addiction as strictly a social problem and may characterize those who take drugs as morally weak. One very common belief is that drug abusers should be able to just stop taking drugs if they are only willing to change their behavior. What people often underestimate is the complexity of drug addiction—that it is a disease that impacts the brain and because of that, stopping drug abuse is not simply a matter of willpower. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives.

What is drug addiction?

Addiction is a chronic, often relapsing brain disease that causes compulsive drug seeking and use despite harmful consequences to the individual that is addicted and to those around them. Drug addiction is a brain disease because the abuse of drugs leads to changes in the structure and function of the brain. Although it is true that for most people the initial decision to take drugs is voluntary, over time the changes in the brain caused by repeated drug abuse can affect a person's self control and ability to make sound decisions, and at the same time send intense impulses to take drugs.

It is because of these changes in the brain that it is so challenging for a person who is addicted to stop abusing drugs. Fortunately, there are treatments that help people to counteract addiction's powerful disruptive effects and regain control. Research shows that combining addiction treatment medications, if available, with behavioral therapy is the best way to ensure success for most patients. Treatment approaches that are tailored to each patient's drug abuse patterns and any co-occurring medical, psychiatric, and social problems can lead to sustained recovery and a life without drug abuse.

Similar to other chronic, relapsing diseases, such as diabetes, asthma, or heart disease, drug addiction can be managed successfully. And, as with other chronic diseases, it is not uncommon for a person to relapse and begin abusing drugs again. Relapse, however, does not signal failure—rather, it indicates that treatment should be reinstated, adjusted, or that alternate treatment is needed to help the individual regain control and recover