Vision Realtors

Muskoka is every golfer’s dream destination in Ontario and with very good reason. This toronto condo exquisite golf destination has some of the most breathtaking backdrops that you can imagine. With outcroppings of granite, white pines that tower high over you, the glorious morning sun and some excellent golf what more could any golfer want? Muskoka is by far one of the most popular golfing destinations in Ontario.

The golf courses

Muskoka boasts of over 32 golf courses that are championship level. Some of these toronto condos courses have been designed by some of the greatest golfers there ever were. In addition to this Muskoka also has other golf courses clubbed together with places to stay. These make ideal vacation destinations with or without family. You can choose from golf resorts,clubs, inns and spas.

The golf trails

Added to all the golf clubs and resorts are 3 of the best trails ever. These incredible courses can be quite affordable depending on when you book them. The Muskoka highlands golf course can match a Scottish links course where shot making challenges are concerned. The Windemere Golf and Country club is packed with tradition and beauty. The Huntsville Downs Golf and Country Club established in 1925, set amongst 200 acres is also worth a visit.

The Muskoka Bay Golf Course

The latest addition to the golf courses in Muskoka is Freed’s Muskoka Bay Golf Course. This toronto condo property is located in the mature woodlands of Gravenhurst. The entire club will be spread over an area of 850 acres. There will be bungalows that are custom built. These bungalows will lie next to the championship 18 – hole golf course designed and developed by Doug Carrick. Doug Carrick is known for developing golf courses while keeping their natural surroundings intact. Similarly the natural settings of this property have not been disturbed. So how difficult is this golf course? With all the natural landscaping intact, walking on this course is next to impossible. However if you get your hands on a golf cart and sit back the ride will be quite enjoyable.

Classification

Alcohol and Health

Short-term effects of alcohol

Long-term effects of alcohol

Alcohol and cardiovascular disease

Alcoholic liver disease

Alcoholic hepatitis

Alcohol and cancer

Alcohol and weight

Fetal alcohol syndrome

Fetal Alcohol Spectrum Disorder

Alcoholism

Blackout (alcohol-related amnesia)

Wernicke-Korsakoff syndrome

Recommended maximum intake

Wine and health

The definitions of alcoholism and related terminology vary significantly between the medical community, treatment programs, and the general public.

Medical definitions

The National Council on Alcoholism and Drug Dependence and The American Society of Addiction Medicine define alcoholism as “a primary, chronic disease characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking.” The DSM-IV (the dominant diagnostic manual in psychiatry and psychology) defines alcohol abuse as repeated use despite recurrent adverse consequences. It further defines alcohol dependence as alcohol abuse combined with tolerance, withdrawal, and an uncontrollable drive to drink. (See DSM diagnosis below.) Within psychology and psychiatry, alcoholism is the popular term for alcohol dependence.

Terminology

Many terms are applied to a drinker’s relationship with alcohol. Use, misuse, heavy use, abuse, addiction, and dependence are all common labels used to describe drinking habits, but the actual meaning of these words can vary greatly depending upon the context in which they are used. Even within the medical field, the definition can vary between areas of specialization. Because alcoholism is often used in a derogatory sense in politics and religion, the meanings of the words surrounding it are often used imprecisely.

Use refers to simple use of a substance. An individual who drinks any alcoholic beverage is using alcohol. Misuse, problem use, abuse, and heavy use refers to improper use of alcohol which may cause physical, social, or moral harm to the drinker.

Moderate Use is defined by The Dietary Guidelines for Americans as no more than two alcoholic beverages per day for men and no more than one alcoholic beverage per day for women.

Risk factors

About 40 percent of those who begin drinking alcohol before age 14 develop alcohol dependence, whereas only 10 percent of those who did not begin drinking until 20 years or older developed an alcohol problem in later life, although it should be born in mind that Correlation does not imply causation. Alcohol abuse during adolescence may lead to long-term changes in the brain which leaves them at increased risk of alcoholism in later years; genetic factors also influence age of onset of alcohol abuse and risk of alcoholism.

The age of onset of drinking as well as genetic factors are associated with an increased risk of the development of alcoholism. Individuals who have a pre-existing vulnerability to alcoholism are also more likely to begin drinking earlier than average. The risk taking behavior associated with adolescence promotes binge drinking. Age and genetic factors influence the risk of developing alcohol related neurotoxicity. Genetic traits which influence the risk of the development of alcoholism are associated with a family history of alcoholism. One published article has found that alcohol use at an early age may itself directly influence the risk of developing alcoholism via influencing the expression of genes which increase the risk of alcohol dependence. It has been hypothesized that this increased risk may be due to the highly sensitive developing adolescent brain which leads to modulating of the genetic state of the brain which in turn primes the adolescent for increased risk of alcohol dependence. About 40 percent of alcoholics were drinking excessively by late adolescence. Most alcoholics develop alcoholism during adolescence or young adulthood. Severe childhood trauma is also associated with an increased risk of alcohol or other drug problems. There is evidence that a complex mixture of genetic factors as well as environmental factors, e.g. stressful childhood events, influence the risk of the development of alcoholism. Genes which influence the metabolism of alcohol also influence the risk of alcoholism. Good peer and family support is associated with a reduced risk of alcoholism developing.

Signs and symptoms

Effects of long term alcohol misuse

Main article: Long-term effects of alcohol

Most significant of the possible long-term effects of ethanol. Additionally, in pregnant women, it causes fetal alcohol syndrome.

The primary effect of alcoholism is to encourage the sufferer to drink at times and in amounts that are damaging to physical health. The secondary damage caused by an inability to control one’s drinking manifests in many ways. Alcoholism also has significant social costs to both the alcoholic and their family and friends. Alcoholism can have adverse effects on mental health causing psychiatric disorders to develop. Approximately 18 percent of alcoholics commit suicide. Research has found that over fifty percent of all suicides are associated with alcohol or drug dependence. In adolescents the figure is higher with alcohol or drug misuse playing a role in up to 70 percent of suicides.

Physical health effects

The physical health effects associated with alcohol consumption may include cirrhosis of the liver, pancreatitis, epilepsy, polyneuropathy, alcoholic dementia, heart disease, increased chance of cancer, nutritional deficiencies, sexual dysfunction, and death from many sources. Severe cognitive problems are not uncommon in alcoholics. Approximately 10% of all dementia cases are alcohol related making alcohol the 2nd leading cause of dementia. Other adverse effects on physical health include an increased risk of developing cardiovascular disease, malabsorption, alcoholic liver disease, and cancer. Damage to the central nervous system and peripheral nervous system can occur from sustained alcohol consumption.

Mental health effects

Long term misuse of alcohol can cause a wide range of mental health effects. Alcohol misuse is not only toxic to the body but also to brain function and thus psychological well being can be adversely affected by the long-term effects of misuse. Psychiatric disorders are common in alcoholics, especially anxiety and depression disorders, with as many as 25% of alcoholics presenting with severe psychiatric disturbances. Typically these psychiatric symptoms caused by alcohol misuse initially worsen during alcohol withdrawal but with abstinence these psychiatric symptoms typically gradually improve or disappear altogether. Psychosis, confusion and organic brain syndrome may be induced by chronic alcohol abuse which can lead to a misdiagnosis of major mental health disorders such as schizophrenia. Panic disorder can develop as a direct result of long term alcohol misuse. Panic disorder can also worsen or occur as part of the alcohol withdrawal syndrome. Chronic alcohol misuse can cause panic disorder to develop or worsen an underlying panic disorder via distortion of the neurochemical system in the brain.

The co-occurrence of major depressive disorder and alcoholism is well documented. Among those with comorbid occurrences, a distinction is commonly made between depressive episodes that are secondary to the pharmacological or toxic effects of heavy alcohol use and remit with abstinence, and depressive episodes that are primary and do not remit with abstinence. Additional use of other drugs may increase the risk of depression in alcoholics. Depressive episodes with an onset prior to heavy drinking or those that continue in the absence of heavy drinking are typically referred to as “independent” episodes, whereas those that appear to be etiologically related to heavy drinking are termed “substance-induced”. There is a high rate of suicide in chronic alcoholics with the risk of suicide increasing the longer a person drinks. The reasons believed to cause the increased risk of suicide in alcoholics include the long-term abuse of alcohol causing physiological distortion of brain chemistry as well as the social isolation which is common in alcoholics. Suicide is also very common in adolescent alcohol abusers, with 1 in 4 suicides in adolescents being related to alcohol abuse.

Social effects

The social problems arising from alcoholism can be massive and are caused in part due to the serious pathological changes induced in the brain from prolonged alcohol misuse and partly because of the intoxicating effects of alcohol. Alcohol abuse is also associated with increased risks of committing criminal offences including child abuse, domestic violence, rapes, burglaries and assaults. Alcoholism is associated with loss of employment, which can lead to financial problems including the loss of living quarters. Drinking at inappropriate times, and behavior caused by reduced judgment, can lead to legal consequences, such as criminal charges for drunk driving or public disorder, or civil penalties for tortious behavior. An alcoholic’s behavior and mental impairment while drunk can profoundly impact those surrounding them and lead to isolation fromfamily and friends, possibly leading to marital conflict and divorce, or contributing to domestic violence. This can contribute to a loss of self-esteem and even lead to jail. Alcoholism can also lead to child neglect, with subsequent lasting damage to the emotional development of the alcoholic’s children, even after they reach adulthood.

Alcohol withdrawal

Main article: Alcohol withdrawal syndrome

Alcohol withdrawal differs significantly from most other drugs in that it can be directly fatal. For example it is extremely rare for heroin withdrawal to be fatal. When people die from heroin or cocaine withdrawal they typically have serious underlying health problems which are made worse by the strain of acute withdrawal. An alcoholic, however, who has no serious health issues, has a significant risk of dying from the direct effects of withdrawal if it is not properly managed. Sedative-hypnotic drugs such as barbiturates and benzodiazepines which have a similar mechanism of action to alcohol (which is also a sedative-hypnotic) also have a similar risk of causing death during withdrawal.

Alcohol’s primary effect is the increase in stimulation of the GABAA receptor, promoting central nervous system depression. With repeated heavy consumption of alcohol, these receptors are desensitized and reduced in number, resulting in tolerance and physical dependence. Thus when alcohol is stopped, especially abruptly, the person’s nervous system suffers from uncontrolled synapse firing. This can result in symptoms that include anxiety, life threatening seizures, delirium tremens and hallucinations, shakes and possible heart failure.

Acute withdrawal symptoms tend to subside after one to three weeks. Less severe symptoms (e.g. insomnia and anxiety, anhedonia) may continue as part of a post withdrawal syndrome gradually improving with abstinence for a year or more. Withdrawal symptoms begin to subside as the body and central nervous system makes adaptations to reverse tolerance and restore GABA function towards normal. Other neurotransmitter systems are involved, especially glutamate and NMDA.

Diagnosis

Multiple tools are available to those wishing to conduct screening for alcoholism. Identification involves an objective assessment regarding the damage that imbibing alcohol does to the drinker’s life compared with the subjective benefits the drinker perceives from consuming alcohol. While there are many cases where an alcoholic’s life has been significantly and obviously damaged, there are always borderline cases that can be difficult to classify.

Addiction Medicine specialists have extensive training with respect to diagnosing and treating patients with alcoholism.

Screening

Several tools may be used to detect a loss of control of alcohol use. These tools are mostly self reports in questionnaire form. Another common theme is a score or tally that sums up the general severity of alcohol use.

The CAGE questionnaire, named for its four questions, is one such example that may be used to screen patients quickly in a doctor’s office.

Two “yes” responses indicate that the respondent should be investigated further. The questionnaire asks the following questions:

Have you ever felt you needed to Cut down on your drinking?

Have people Annoyed you by criticizing your drinking?

Have you ever felt Guilty about drinking?

Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?

The CAGE questionnaire, has demonstrated a high effectiveness in detecting alcohol related problems; however, it has limitations in people with less severe alcohol related problems, white women and college students.

The Alcohol Dependence Data Questionnaire is a more sensitive diagnostic test than the CAGE test. It helps distinguish a diagnosis of alcohol dependence from one of heavy alcohol use.

The Michigan Alcohol Screening Test (MAST) is a screening tool for alcoholism widely used by courts to determine the appropriate sentencing for people convicted of alcohol-related offenses, driving under the influence being the most common.

The Alcohol Use Disorders Identification Test (AUDIT) is a screening questionnaire developed by the World Health Organization. This test is unique in that it has been validated in six countries and is used internationally. Like the CAGE questionnaire, it uses a simple set of questions – a high score earning a deeper investigation.

The Paddington Alcohol Test (PAT) was designed to screen for alcohol related problems amongst those attending Accident and Emergency departments. It concords well with the AUDIT questionnaire but is administered in a fifth of the time.

Genetic predisposition testing

Psychiatric geneticists John I. Nurnberger, Jr., and Laura Jean Bierut suggest that alcoholism does not have a single causencluding geneticut that genes do play an important role “by affecting processes in the body and brain that interact with one another and with an individual’s life experiences to produce protection or susceptibility.” They also report that fewer than a dozen alcoholism-related genes have been identified, but that more likely await discovery.

At least one genetic test exists for an allele that is correlated to alcoholism and opiate addiction. Human dopamine receptor genes have a detectable variation referred to as the DRD2 TaqI polymorphism. Those who possess the A1 allele (variation) of this polymorphism have a small but significant tendency towards addiction to opiates and endorphin releasing drugs like alcohol. Although this allele is slightly more common in alcoholics and opiate addicts, it is not by itself an adequate predictor of alcoholism, and some researchers argue that evidence for DRD2 is contradictory.

DSM diagnosis

The DSM-IV diagnosis of alcohol dependence represents one approach to the definition of alcoholism. In part this is to assist in the development of research protocols in which findings can be compared with one another. According to the DSM-IV, an alcohol dependence diagnosis is:

…maladaptive alcohol use with clinically significant impairment as manifested by at least three of the following within any one-year period: tolerance; withdrawal; taken in greater amounts or over longer time course than intended; desire or unsuccessful attempts to cut down or control use; great deal of time spent obtaining, using, or recovering from use; social, occupational, or recreational activities given up or reduced; continued use despite knowledge of physical or psychological sequelae.

Urine and blood tests

There are reliable tests for the actual use of alcohol, one common test being that of blood alcohol content (BAC). These tests do not differentiate alcoholics from non-alcoholics; however, long-term heavy drinking does have a few recognizable effects on the body, including:

Macrocytosis (enlarged MCV)1

Elevated GGT

Moderate elevation of AST and ALT and an AST: ALT ratio of 2:1.

High carbohydrate deficient transferrin (CDT)

However, none of these blood tests for biological markers are as sensitive as screening questionaires.

Prevention

Because alcohol use disorders are perceived as impacting society as a whole, World Health Organization, the European Union and other regional bodies, national governments and parliaments have formed alcohol policies in order to reduce the harm of alcoholism.

To combat the health, social and educational underachievement which results from alcohol or drug dependence targeting adolescents and young adults is regarded as an important step to reduce the harm of alcohol abuse. The age at which licit drugs of abuse such as alcohol can be purchased as well as banning or restricting advertising of alcohol has been recommended. Credible and evidence based educational drives in the mass media about the consequences of alcohol and other drug abuse has also been recommended. Guidelines for parents on alcohol and drug use during adolescence and targeting young people with mental health problems has also been suggested to prevent the harm of alcohol and other drug abuse.

Management

Treatments for alcoholism (antidipsotropic) are quite varied because there are multiple perspectives for the condition itself. Those who approach alcoholism as a medical condition or disease recommend differing treatments than, for instance, those who approach the condition as one of social choice.

Most treatments focus on helping people discontinue their alcohol intake, followed up with life training and/or social support in order to help them resist a return to alcohol use. Since alcoholism involves multiple factors which encourage a person to continue drinking, they must all be addressed in order to successfully prevent a relapse. An example of this kind of treatment is detoxification followed by a combination of supportive therapy, attendance at self-help groups, and ongoing development of coping mechanisms. The treatment community for alcoholism typically supports an abstinence-based zero tolerance approach; however, there are some who promote a harm-reduction approach as well.

Effectiveness

When considering the effectiveness of treatment options, one must consider the success rate based on those who enter a program, not just those who complete it. Since completion of a program is the qualification for success, success among those who complete a program is generally near 100%. It is also important to consider not just the rate of those reaching treatment goals but the rate of those relapsing. Results should also be compared to the roughly 5% rate at which people will quit on their own. A year after completing a rehab program, about a third of alcoholics are sober, an additional 40 percent are substantially improved but still drink heavily on occasion, and a quarter have completely relapsed.

Detoxification

Main article: Alcohol detoxification

Alcohol detoxification or ‘detox’ for alcoholics is an abrupt stop of alcohol drinking coupled with the substitution of drugs that have similar effects to prevent alcohol withdrawal.

Detoxification treats the physical effects of prolonged use of alcohol, but does not actually treat alcoholism. After detox is complete, relapse is likely without further treatment. These rehabilitations (or ‘rehabs’) may take place in an inpatient or outpatient setting.

Group therapy and psychotherapy

A regional service center for Alcoholics Anonymous.

After detoxification, various forms of group therapy or psychotherapy can be used to deal with underlying psychological issues that are related to alcohol addiction, as well as provide relapse prevention skills.

The mutual-help group-counseling approach is one of the most common ways of helping alcoholics maintain sobriety. Many organizations have been formed to provide this service. Alcoholics Anonymous was the first group, and has more members than all other programs combined. Some of the others include LifeRing Secular Recovery, Rational Recovery, SMART Recovery, and Women For Sobriety.

Rationing and moderation

Rationing and moderation programs such as Moderation Management and DrinkWise do not mandate complete abstinence. While most alcoholics are unable to limit their drinking in this way, some return to moderate drinking. A 2002 U.S. study by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) showed that 17.7% of individuals diagnosed as alcohol dependent more than one year prior returned to low-risk drinking. This group, however, showed fewer initial symptoms of dependency. A follow-up study, using the same subjects that were judged to be in remission in 2001-2002, examined the rates of return to problem drinking in 2004-2005. The study found abstinence from alcohol was the most stable form of remission for recovering alcoholics. A long-term (60 year) follow-up of two groups of alcoholic men concluded that “return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence.”

Medications

A variety of medications may be prescribed as part of treatment for alcoholism.

Medications currently in use

Antabuse (disulfiram) prevents the elimination of acetaldehyde, a chemical the body produces when breaking down ethanol. Acetaldehyde itself is the cause of many hangover symptoms from alcohol use. The overall effect is severe discomfort when alcohol is ingested: an extremely fast-acting and long-lasting uncomfortable hangover. This discourages an alcoholic from drinking in significant amounts while they take the medicine. A recent 9-year study found that incorporation of supervised disulfiram and a related compound carbamide into a comprehensive treatment program resulted in an abstinence rate of over 50%.

Temposil (calcium carbimide) works in the same way as Antabuse, but is weaker and safer[citation needed].

Naltrexone is a competitive antagonist for opioid receptors, effectively blocking our ability to use endorphins and opiates. Alcohol causes the body to release endorphins, hence when naltrexone is in the body drinkers no longer get any pleasure from consuming alcohol. Naltrexone is used in two very different forms of treatment. The first treatment uses naltrexone to decrease cravings for alcohol and encourage abstinence. The other treatment, called pharmacological extinction, combines naltrexone with normal drinking habits in order to reverse the endorphin conditioning that causes alcohol addiction. This results in a reduced desire to drink that persists after naltrexone use is discontinued, as long as the patient always takes naltrexone before drinking.

Naltrexone comes in two forms. Oral naltrexone (originally but no longer available as the brand ReVia) is a pill that must be taken one hour before drinking to be effective. Vivitrol is a time-release formulation that is injected in the buttocks once a month.

Acamprosate (also known as Campral) is thought to stabilize the chemical balance of the brain that would otherwise be disrupted by alcoholism. The Food and Drug Administration (FDA) approved this drug in 2004, saying “While its mechanism of action is not fully understood, Campral is thought to act on the brain pathways related to alcohol abuse… Campral proved superior to placebo in maintaining abstinence for a short period of time…” The COMBINE study was unable to demonstrate efficacy for Acamprosate.

Experimental Medications

Many experimental medications are presently in clinical trials for the treatment of alcoholism. Promising results have been obtained with anticonvulsant drugs usually used to treat epilepsy.

Topiramate (brand name Topamax), a derivative of the naturally occurring sugar monosaccharide D-fructose, has been found effective in helping alcoholics quit or cut back on the amount they drink. In one study heavy drinkers were six times more likely to remain abstinent for a month if they took the medication, even in small doses. In another study, those who received topiramate had fewer heavy drinking days, fewer drinks per day and more days of continuous abstinence than those who received the placebo. Evidence suggests that topiramate antagonizes excitatory glutamate receptors, inhibits dopamine release, and enhances inhibitory gamma-aminobutyric acid function. A 2008 review of the effectiness of topiramate concluded that the results of published trials are promising, however at this time, data are insufficient to support using topiramate in conjunction with brief weekly compliance counseling as a first-line agent for alcohol dependence.

Medications which may worsen outcome

Benzodiazepines, whilst useful in the management of acute alcohol withdrawal, if used long-term cause a worse outcome in alcoholism. Alcoholics on chronic benzodiazepines have a lower rate of achieving abstinence from alcohol than those not taking benzodiazepines. This class of drugs are commonly prescribed to alcoholics for insomnia or anxiety management. Initiating prescriptions of Benzodiazepines or sedative-hypnotics in individuals in recovery has a high rate of relapse with one author reporting more than a quarter of people relapse after being prescribed sedative-hypnotics. Patients often mistakenly think that they are sober despite continuing to take benzodiazepines. Those who are long-term users of benzodiazepines should not be withdrawn rapidly, taper regimes of 612 months have been found to be the most successful, with reduced intensity of withdrawal.

Dual addictions

The AMA definition of alcoholism refers to a disease entity involving the compulsive use of alcohol despite social, physical and mental harm.[citation needed]. The DSM-IV definition of alcohol dependence refers to alcohol only, and DSM-IV uses sedative dependence to refer to the disease entity involving non-alcohol sedative agents.[citation needed]

Alcoholics may also require treatment for other psychotropic drug addictions. The most common dual addiction in alcohol dependence is a benzodiazepine dependence with studies showing 10 – 20% of alcohol dependent individuals having problems of dependence and/or misuse problems of benzodiazepines. Alcohol itself is a sedative-hypnotic and is cross-tolerant with other sedative-hypnotics such as barbiturates, benzodiazepines and the nonbenzodiazepines. Dependence on other sedative hypnotics such as zolpidem and zopiclone as well as opiates and illegal drugs is common in alcoholics. Dependence and withdrawal from sedative hypnotics, eg benzodiazepine withdrawal is similar to alcohol and can be medically severe and include the risk of psychosis and seizures if not managed properly. Benzodiazepine dependency requires careful reduction in dosage to avoid a serious benzodiazepine withdrawal syndrome and health consequences. Benzodiazepines have the problem of increasing cravings for alcohol in problem alcohol consumers. Benzodiazepines also increase the volume of alcohol consumed by problem drinkers.

Epidemiology

Disability-adjusted life year for alcohol use disorders per 100,000 inhabitants in 2002.

     no data      less than 50      50-150      150-250      250-350      350-450      450-550      550-650      650-750      750-850      850-950      950-1050      more than 1050

Total recorded yearly alcohol per capita consumption (15+), in litres of pure alcohol

Substance use disorders are a major public health problem facing many countries. “The most common substance of abuse/dependence in patients presenting for treatment is alcohol.” In the United Kingdom, the number of ‘dependent drinkers’ was calculated as over 2.8 million in 2001. The World Health Organization estimates that about 140 million people throughout the world suffer from alcohol dependence. In the United States and western Europe 10 to 20% of men and 5 to 10% of women at some point in their lives will meet criteria for alcoholism.

Within the medical and scientific communities, there is broad consensus regarding alcoholism as a disease state. For example, the American Medical Association considers alcohol a drug and states that “drug addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite often devastating consequences. It results from a complex interplay of biological vulnerability, environmental exposure, and developmental factors (e.g., stage of brain maturity).”

Current evidence indicates that in both men and women, alcoholism is 50-60% genetically determined, leaving 40-50% for environmental influences.

A 2002 study by the National Institute on Alcohol Abuse and Alcoholism surveyed a group of 4,422 adults meeting the criteria for alcohol dependence and found that after one year, some met the authors’ criteria for low-risk drinking, even though only 25.5% of the group received any treatment, with the breakdown as follows:

25% still dependent

27.3% in partial remission (some symptoms persist)

11.8% asymptomatic drinkers (consumption increases chances of relapse)

35.9% fully recovered made up of 17.7% low-risk drinkers plus 18.2% abstainers.

In contrast, however, the results of a long term (60 year) follow-up of two groups of alcoholic men by George Vaillant at Harvard Medical School indicated that “return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence.” Vaillant also noted that “return-to-controlled drinking, as reported in short-term studies, is often a mirage.”

History

Etymology

1904 advertisement describing alcoholism as a disease.

The term “alcoholism” was first used in 1849 by the Swedish physician Magnus Huss to describe the systematic adverse effects of alcohol.

In the United States, use of the word “alcoholism” was largely popularized by the founding and growth of Alcoholics Anonymous in 1935[citation needed]. AA’s basic text, known as the “Big Book,” describes alcoholism as an illness that involves a physical allergy:p.xxviii and a mental obsession.:p.23 Note that the definition of “allergy” used in this context is not the same as used in modern medicine. . The doctor and addiction specialist Dr. William D. Silkworth M.D. writes on behalf of AA that Alcoholics suffer from a “(physical) craving beyond mental control”.

A 1960 study by E. Morton Jellinek is considered the foundation of the modern disease theory of alcoholism. Jellinek’s definition restricted the use of the word “alcoholism” to those showing a particular natural history. The modern medical definition of alcoholism has been revised numerous times since then. The American Medical Association currently uses the word alcoholism to refer to a particular chronic primary disease.

A minority opinion within the field, notably advocated by Herbert Fingarette and Stanton Peele, argue against the existence of alcoholism as a disease. Critics of the disease model tend to use the term “heavy drinking” when discussing the negative effects of alcohol consumption.

Society and culture

The various health problems associated with long-term alcohol consumption are generally perceived as detrimental to society, for example, money due to lost labor-hours, medical costs, and secondary treatment costs. Alcohol use is a major contributing factor for head injuries, motor vehicle accidents, violence, and assaults. Beyond money, there is also the pain and suffering of the individuals besides the alcoholic affected. For instance, alcohol consumption by a pregnant woman can lead to Fetal alcohol syndrome, an incurable and damaging condition.

Estimates of the economic costs of alcohol abuse, collected by the World Health Organization, vary from one to six per cent of a country’s GDP. One Australian estimate pegged alcohol’s social costs at 24 per cent of all drug abuse costs; a similar Canadian study concluded alcohol’s share was 41 per cent.

A study quantified the cost to the UK of all forms of alcohol misuse as 18.520 billion annually (2001 figures).

Stereotypes

Depiction of a wino or town drunk

Stereotypes of alcoholics are often found in fiction and popular culture. The ‘town drunk’ is a stock character in Western popular culture.

Stereotypes of drunkenness may be based on racism or xenophobia, as in the depiction of the Irish as heavy drinkers.

Studies by social psychologists Stivers and Greeley attempt to document the perceived prevalence of high alcohol consumption amongst the Irish in America.

Alcohol-related crime

See also: Drug-related crime

This section may require cleanup to meet Wikipedia’s quality standards. Please improve this section if you can. (July 2009)

Of the adult US population, at least 75% are drinkers; and about 6% of the total group are alcoholics. In groups which are almost 100% drinkers, the alcoholism rate is about 8%. Many reports state that about 73% of felonies are alcohol-related. One survey shows that in about 67% of child-beating cases, 41% of forcible rape cases, 80% of wife-battering, 72% of stabbings, and 83% of homicides, either the attacker or the victim or both had been drinking.”

In film and literature

In modern times, the recovery movement has led to more realistic depictions of problems that stem from heavy alcohol use. Authors such as Charles R. Jackson and Charles Bukowski describe their own alcohol addiction in their writings. The disjointed narrative of Patrick Hamilton’s Hangover Square reflects the alcoholism of its central character. A famous depiction of alcoholism, and the psychology of an alcoholic, is in Malcolm Lowry’s widely acclaimed novel Under the Volcano, which details the final day of the British consul Geoffrey Firmin on the Day of the Dead in 1939 Mexico and his choice to continue his extreme alcohol consumption instead of returning to the wife he loves.

Films like Bad Santa, Barfly, Days of Wine and Roses, Ironweed, My Name Is Bill W., Withnail and I, Arthur, Leaving Las Vegas, When a Man Loves a Woman, Shattered Spirits and The Lost Weekend chronicle similar stories of alcoholism.

Women and alcoholism

Alcoholism has a higher prevalence among men, though in recent decades, the proportion of female alcoholics has increased. It is important to articulate the different biological and social ways alcoholism manifests in women in order to understand barriers to treatment and effective recovery strategies.

William Hogarth’s Gin Lane, 1751.

Biological differences and physiological effects

Biologically, women have symptom profiles from their alcohol use that differ in important ways from men. They experience a telescoping of physiological effects from alcohol use. Equal dosages of alcohol consumed by men and women generally result in women having higher blood alcohol concentrations (BACs). This can be attributed to many reasons, the main being that women have less body water than men. A given amount of alcohol, therefore becomes more highly concentrated in a woman’s body. Besides this fact, women also become more intoxicated, which is due to different hormone release.

Women develop long-term complications of alcohol dependence more rapidly than do alcoholic men. Additionally, women have a higher mortality rate from alcoholism than men. Examples of long term complications include brain, heart, and liver damage and an increased risk for breast cancer (see alcohol and breast cancer). Additionally, heavy drinking over time has been found to have a negative effect on reproductive functioning in women. This results in reproductive dysfunction such as anovulation, decreased ovarian mass, irregular menses, amenorrhea, luteal phase dysfunction, and early menopause.

Psychological and emotional effects

Psychiatric disorders are generally more prevalent among those with alcohol disorders. This is true for both men and women, however the disorders differ depending on gender. Women who have alcohol-use disorders often have co-occurring psychiatric diagnosis such as major depression, anxiety, panic disorder, bulimia, post-traumatic stress disorder (PTSD), or borderline personality disorder. Men with alcohol-use disorders more often have co-occurring diagnosis of narcissistic and antisocial personality disorders, bipolar disorder, schizophrenia, impulse disorders and attention deficit/ hyperactivity disorder.

Women with alcoholism are also more likely to have a history of physical or sexual assault, abuse and domestic violence than those in the general population. This trauma can lead to higher instances of PTSD, depression, anxiety, and a greater dependence on alcohol.

Societal barriers to treatment

Attitudes and social stereotypes about women and alcohol can create barriers to the detection and treatment of female alcohol abusers. Such beliefs stigmatize women who drink by characterizing them as “both generally and sexually immoral” or the “fallen women.” Fear of stigmatization may lead women to deny that they are suffering from a medical condition, to hide their drinking, and to drink alone. This pattern, in turn, leads family, physicians, and others to be less likely to suspect that a woman they know is an alcoholic.

In contrast, attitudes and social stereotypes about men and alcohol can lower barriers to the detection and treatment of male alcohol abusers. Such beliefs reward men who drink by characterizing them as “both generally and sexually moral” or the “risen men.” Reduced fear of stigma may lead men to admit that they are suffering from a medical condition, to publicly display their drinking, and to drink in groups. This pattern, in turn, leads family, physicians, and others to be more likely to suspect that a man they know is an alcoholic. Women also tend to have a greater fear that the negative implications from the stigma will reflect poorly on their families. This may also keep them from seeking help.

Implications for treatment

Research has indicated a lack of adequate training for practitioners both in problematic alcohol use in general, and in relation to women’s issues. The complexity of alcohol use disorders, particularly with gender-related issues, indicates that the need for practitioners’ knowledge, insight and compassion is enormous. Better education and awareness surrounding the gender implications of alcoholism will help care providers to adequately treat women who suffer from alcoholism. Early intervention will also increase the probability of recovery.

See also

Wikiquote has a collection of quotations related to: Alcoholism

Wikimedia Commons has media related to: Alcoholism

Alcohol consumption and health

Alcoholism in family systems

Alcohol dementia

Alcohol-related traffic crashes

Alcohol tolerance

Alcohol withdrawal syndrome

Alcoholic lung disease

Binge drinking

List of countries by alcohol consumption

Alcohol intoxication

E. Morton Jellinek

Ethanol Metabolism biochemical discussion of alcohol metabolism

Handbook on Drug and Alcohol Abuse

Hangover

List of deaths through alcohol

Substance abuse

Self-medication

Wernicke-Korsakoff syndrome

Willingway Hospital

Medical diagnostics to test for alcohol use

Blood alcohol content

Full blood count

Liver function tests

Al-Anon and Alateen: support groups for friends and families affected by alcoholism

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The Sarasota MLS service offers you the comfort of searching for a new home from a private area, with no pressure from a sales agent or other prospective buyers. Simply choose the type of property you are searching for, and the homes available are populated for you to see. The information given in each ad tells you about the area, the square footage of the home, as well as the age of the property and asking price. There are many different realtors that contribute this information to the MLS service, and this is what makes the search easier for you. If you were to search the Internet for all the different realtors in Sarasota, there is no guarantee you would find a home you truly loved. With the MLS service, you can sit in one location and look at all the homes and condos for sale in Sarasota and the surrounding islands, to find what is right for you.

With all the properties and amenities that are offered in Sarasota and Manatee County, the Sarasota MLS service not only creates a user friendly environment for you to search, but also makes the search less time consuming. With sales personnel always trying to make a sale, this option gives you control of the situation and allows you to choose your own route.

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Realtors in Middle TN http://www.RealEstate-CentralTN.com http://www.RealEstate-CentralTN.com Realtors in Middle TN 1 717-4031. Are you short of really useful and well informed realtors in middle TN? We provide a wide-range of real estate services which will make the process of buying or selling a property in middle TN a pleasurable experience.

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Purchasing or selling a home or property is a big event in someone’s life and they want to be certain to work with someone that is committed to looking out for their best interest. In the present real estate market, conditions change on a day-to-day basis and this is another reason to find realtors in middle TN who are up to date on the local conditions. Please be at liberty to call us anytime at 1 ( 877 ) 717-4031 or have a look at our website www.RealEstate-CentralTN.com.

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Calgary Mls Listings places Calgary at a place not very low in the list. As because Calgary is a very popular tourist place so it tends to have a quite high demand for the real estate business. The most important function of the multiple listing services is it is a list for the brokers of the real estate and an idea of the compensation. In other words the multiple listing services enable the people to publish an offer of compensation of unilateral nature.

This enables the listed broker with his compensation to be viewed by the other participant brokers in the list. If one is to simplify the idea it means that the charges of all the brokers who are enlisted in the list help the cooperative brokers to have an idea of all these things. However this compensation can be well negotiated between both the party of brokers who are listed who are not listed in this case the listed brokers compensate on the grounds of the people and customers the are representing. Since the amount of brokerage and all other sorts of information regarding the details of the need of the customer are made available on the list, this multiple listing services works the best in the favor of the brokers who work in regards to the participants and thus it is the customer part which gets the best profit in this case. As such all the data of the customer are maintained with accurate date and time. Calgary Mls Listings thus seem to have a good place in the multiple listing services as because Calgary is nice place and many people would like to have a good home there.

Another benefit which can be discussed in the case of discussing the multiple listing services is that they tend to make a subscriber search the multiple listing services in detail and get every single piece of information which is listed with the listed brokers.

Function

EGFR (epidermal growth factor receptor) exists on the cell surface and is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor (TGF) (note, a full list of the ligands able to activate EGFR and other members of the ErbB family is given in the ErbB article). ErbB2 has no known direct activating ligand, and may be in an activated state constitutively or become active upon heterodimerization with other family members such as EGFR.

Upon activation by its growth factor ligands, EGFR undergoes a transition from an inactive monomeric form to an active homodimer – although there is some evidence that preformed inactive dimers may also exist before ligand binding[citation needed]. In addition to forming homodimers after ligand binding, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. There is also evidence to suggest that clusters of activated EGFRs form, although it remains unclear whether this clustering is important for activation itself or occurs subsequent to activation of individual dimers[citation needed].

Diagram of the EGF receptor highlighting important domains

EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of several tyrosine (Y) residues in the C-terminal domain of EGFR occurs. These include Y992, Y1045, Y1068, Y1148 and Y1173 as shown in the diagram to the left. This autophosphorylation elicits downstream activation and signaling by several other proteins that associate with the phosphorylated tyrosines through their own phosphotyrosine-binding SH2 domains. These downstream signaling proteins initiate several signal transduction cascades, principally the MAPK, Akt and JNK pathways, leading to DNA synthesis and cell proliferation. Such proteins modulate phenotypes such as cell migration, adhesion, and proliferation. Activation of the receptor is important for the innate immune response in human skin . The kinase domain of EGFR can also cross-phosphorylate tyrosine residues of other receptors it is aggregated with, and can itself be activated in that manner.

Clinical applications

Mutations that lead to EGFR over[removed]known as upregulation) or overactivity have been associated with a number of cancers, including lung cancer, anal cancers and glioblastoma multiforme. In this latter case a more or less specific mutation of EGFR, called EGFRvIII is often observed. Mutations, amplifications or misregulations of EGFR or family members are implicated in about 30% of all epithelial cancers.

Mutations involving EGFR could lead to its constant activation which could result in uncontrolled cell division a predisposition for cancer. Consequently, mutations of EGFR have been identified in several types of cancer, and it is the target of an expanding class of anticancer therapies.

The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR, including gefitinib and erlotinib for lung cancer, and cetuximab for colon cancer.

Many therapeutic approaches are aimed at the EGFR. Cetuximab and panitumumab are examples of monoclonal antibody inhibitors. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody dependent cellular cytotoxicity can be quite different. Other monoclonals in clinical development are zalutumumab, nimotuzumab, and matuzumab. Gefitinib, erlotinib, and lapatinib (mixed EGFR and ERBB2 inhibitor) are examples of small molecule kinase inhibitors. The monoclonal antibodies block the extracellular ligand binding domain. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase. Another method is using small molecules to inhibit the EGFR tyrosine kinase, which is on the cytoplasmic side of the receptor. Without kinase activity, EGFR is unable to activate itself, which is a prerequisite for binding of downstream adaptor proteins. Ostensibly by halting the signaling cascade in cells that rely on this pathway for growth, tumor proliferation and migration is diminished. There are several quantitative methods available that use protein phosphorylation detection to identify EGFR family inhibitors.

Efficient conversion of strongly absorbed light by plasmonic gold nanoparticles to heat energy and their easy bioconjugation suggest their use as selective photothermal agents in molecular cancer cell targeting. Two oral squamous carcinoma cell lines (HSC 313 and HOC 3 Clone and one benign epithelial cell line (HaCaT) were incubated with anti-epithelial growth factor receptor (EGFR) antibody conjugated gold nanoparticles and then exposed to continuous visible argon ion laser at 514 nm. It is found that the malignant cells require less than half the laser energy to be killed than the benign cells after incubation with anti-EGFR antibody conjugated Au nanoparticles. No photothermal destruction is observed for all types of cells in the absence of nanoparticles at four times energy required to kill the malignant cells with anti-EGFR/Au conjugates bonded. Au nanoparticles thus offer a novel class of selective photothermal agents using a CW laser at low powers.

In July 2007 it was discovered that the blood clotting protein fibrinogen activates EGFR, thereby blocking regrowth of injured neuronal cells in the spine. Other natural inhibitors include potato carboxypeptidase inhibitor (PCI), which contains a small cysteine-rich module, called a T-knot scaffold, that is shared by several different protein families, including the EGF family. Structural similarities with these factors can explain the antagonistic effect of PCI.

EGFR and Lung Cancer

New drugs such as Tarceva directly target the EGFR. Patients have been divided into EGFR positive and negative, based upon whether a tissue test shows a mutation. EGFR positive patients have shown an impressive 60% response rate which exceeds the response rate for conventional chemotherapy.[citation needed]

Interactions

Epidermal growth factor receptor has been shown to interact with PLCG1, NCK1, Janus kinase 2, CDC25A, MUC1, Caveolin 1, STAT5A, PTPN1, CRK, SHC1, Beta-catenin, PTPN11, PTPN6, STAT1, CBLC, Src, Androgen receptor, STAT3, GRB14, Grb2, PLSCR1, Wiskott-Aldrich syndrome protein, SH2D3A, Epidermal growth factor, CBLB, Cbl gene, ARF4, PKC alpha, SOS1, SH3KBP1, Caveolin 3, Decorin, NCK2 and Ubiquitin C.

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^ Stortelers, Catelijne; Souriau Christelle, van Liempt Ellis, van de Poll Monique L M, van Zoelen Everardus J J (Jul. 2002). “Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display”. Biochemistry (United States) 41 (27): 873241. ISSN 0006-2960. PMID 12093292. 

^ a b Ettenberg, S A; Keane M M, Nau M M, Frankel M, Wang L M, Pierce J H, Lipkowitz S (Mar. 1999). “cbl-b inhibits epidermal growth factor receptor signaling”. Oncogene (ENGLAND) 18 (10): 185566. doi:10.1038/sj.onc.1202499. ISSN 0950-9232. PMID 10086340. 

^ a b Pennock, Steven; Wang Zhixiang (May. 2008). “A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation”. Mol. Cell. Biol. (United States) 28 (9): 302037. doi:10.1128/MCB.01809-07. PMID 18316398. 

^ a b Umebayashi, Kyohei; Stenmark Harald, Yoshimori Tamotsu (Aug. 2008). “Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation”. Mol. Biol. Cell (United States) 19 (8): 345462. doi:10.1091/mbc.E07-10-0988. PMID 18508924. 

^ Ng, Cherlyn; Jackson Rebecca A, Buschdorf Jan P, Sun Qingxiang, Guy Graeme R, Sivaraman J (Mar. 2008). “Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates”. EMBO J. (England) 27 (5): 80416. doi:10.1038/emboj.2008.18. PMID 18273061. 

^ Kim, Sung-Woo; Hayashi Masaaki, Lo Jeng-Fan, Yang Young, Yoo Jin-San, Lee Jiing-Dwan (Jan. 2003). “ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation”. J. Biol. Chem. (United States) 278 (4): 26618. doi:10.1074/jbc.M205819200. ISSN 0021-9258. PMID 12446727. 

^ Gauthier, Mona L; Torretto Cheryl, Ly John, Francescutti Valerie, O’Day Danton H (Aug. 2003). “Protein kinase Calpha negatively regulates cell spreading and motility in MDA-MB-231 human breast cancer cells downstream of epidermal growth factor receptor”. Biochem. Biophys. Res. Commun. (United States) 307 (4): 83946. ISSN 0006-291X. PMID 12878187. 

^ Qian, X; Esteban L, Vass W C, Upadhyaya C, Papageorge A G, Yienger K, Ward J M, Lowy D R, Santos E (Feb. 2000). “The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties”. EMBO J. (ENGLAND) 19 (4): 64254. doi:10.1093/emboj/19.4.642. ISSN 0261-4189. PMID 10675333. 

^ Qian, X; Vass W C, Papageorge A G, Anborgh P H, Lowy D R (Feb. 1998). “N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains”. Mol. Cell. Biol. (UNITED STATES) 18 (2): 7718. ISSN 0270-7306. PMID 9447973. 

^ Soubeyran, Philippe; Kowanetz Katarzyna, Szymkiewicz Iwona, Langdon Wallace Y, Dikic Ivan (Mar. 2002). “Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors”. Nature (England) 416 (6877): 1837. doi:10.1038/416183a. ISSN 0028-0836. PMID 11894079. 

^ Szymkiewicz, Iwona; Kowanetz Katarzyna, Soubeyran Philippe, Dinarina Ana, Lipkowitz Stanley, Dikic Ivan (Oct. 2002). “CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases”. J. Biol. Chem. (United States) 277 (42): 3966672. doi:10.1074/jbc.M205535200. ISSN 0021-9258. PMID 12177062. 

^ Santra, Manoranjan; Reed Charles C, Iozzo Renato V (Sep. 2002). “Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope”. J. Biol. Chem. (United States) 277 (38): 3567181. doi:10.1074/jbc.M205317200. ISSN 0021-9258. PMID 12105206. 

^ Iozzo, R V; Moscatello D K, McQuillan D J, Eichstetter I (Feb. 1999). “Decorin is a biological ligand for the epidermal growth factor receptor”. J. Biol. Chem. (UNITED STATES) 274 (8): 448992. ISSN 0021-9258. PMID 9988678. 

^ Chen, M; She H, Davis E M, Spicer C M, Kim L, Ren R, Le Beau M M, Li W (Sep. 1998). “Identification of Nck family genes, chromosomal localization, expression, and signaling specificity”. J. Biol. Chem. (UNITED STATES) 273 (39): 251718. ISSN 0021-9258. PMID 9737977. 

^ Tu, Y; Li F, Wu C (Dec. 1998). “Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways”. Mol. Biol. Cell (UNITED STATES) 9 (12): 336782. ISSN 1059-1524. PMID 9843575. 

^ Sehat, Bita; Andersson Sandra, Girnita Leonard, Larsson Olle (Jul. 2008). “Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis”. Cancer Res. (United States) 68 (14): 566977. doi:10.1158/0008-5472.CAN-07-6364. PMID 18632619. 

External links

MeSH Epidermal Growth Factor Receptor

Further reading

Carpenter G (1987). “Receptors for epidermal growth factor and other polypeptide mitogens”. Annu. Rev. Biochem. 56: 881914. doi:10.1146/annurev.bi.56.070187.004313. PMID 3039909. 

Boonstra J, Rijken P, Humbel B, et al. (1995). “The epidermal growth factor”. Cell Biol. Int. 19 (5): 41330. doi:10.1006/cbir.1995.1086. PMID 7640657. 

Carpenter G (2000). “The EGF receptor: a nexus for trafficking and signaling”. Bioessays 22 (8): 697707. doi:10.1002/1521-1878(200008)22:8<697::AID-BIES3>3.0.CO;2-1. PMID 10918300. 

Filardo EJ (2002). “Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer”. J. Steroid Biochem. Mol. Biol. 80 (2): 2318. doi:10.1016/S0960-0760(01)00190-X. PMID 11897506. 

Tiganis T (2002). “Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor”. IUBMB Life 53 (1): 314. doi:10.1080/15216540210811. PMID 12018405. 

Di Fiore PP, Scita G (2002). “Eps8 in the midst of GTPases”. Int. J. Biochem. Cell Biol. 34 (10): 117883. doi:10.1016/S1357-2725(02)00064-X. PMID 12127568. 

Benaim G, Villalobo A (2002). “Phosphorylation of calmodulin. Functional implications”. Eur. J. Biochem. 269 (15): 361931. doi:10.1046/j.1432-1033.2002.03038.x. PMID 12153558. 

Leu TH, Maa MC (2004). “Functional implication of the interaction between EGF receptor and c-Src”. Front. Biosci. 8: s2838. doi:10.2741/980. PMID 12456372. 

Anderson NL, Anderson NG (2003). “The human plasma proteome: history, character, and diagnostic prospects”. Mol. Cell Proteomics 1 (11): 84567. PMID 12488461. 

Kari C, Chan TO, Rocha de Quadros M, Rodeck U (2003). “Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage”. Cancer Res. 63 (1): 15. PMID 12517767. 

Bonaccorsi L, Muratori M, Carloni V, et al. (2003). “Androgen receptor and prostate cancer invasion”. Int. J. Androl. 26 (1): 215. doi:10.1046/j.1365-2605.2003.00375.x. PMID 12534934. 

Reiter JL, Maihle NJ (2003). “Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in human placenta”. Ann. N. Y. Acad. Sci. 995: 3947. PMID 12814937. 

Adams TE, McKern NM, Ward CW (2005). “Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor”. Growth Factors 22 (2): 8995. PMID 15253384. 

Ferguson KM (2005). “Active and inactive conformations of the epidermal growth factor receptor”. Biochem. Soc. Trans. 32 (Pt 5): 7425. doi:10.1042/BST0320742. PMID 15494003. 

Chao C, Hellmich MR (2005). “Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor”. Growth Factors 22 (4): 2618. doi:10.1080/08977190412331286900. PMID 15621729. 

Carlsson J, Ren ZP, Wester K, et al. (2006). “Planning for intracavitary anti-EGFR radionuclide therapy of gliomas. Literature review and data on EGFR expression”. J. Neurooncol. 77 (1): 3345. doi:10.1007/s11060-005-7410-z. PMID 16200342. 

Scartozzi M, Pierantoni C, Berardi R, et al. (2006). “Epidermal growth factor receptor: a promising therapeutic target for colorectal cancer”. Anal. Quant. Cytol. Histol. 28 (2): 618. PMID 16637508. 

Prudkin L, Wistuba II (2006). “Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications”. Annals of diagnostic pathology 10 (5): 30615. doi:10.1016/j.anndiagpath.2006.06.011. PMID 16979526. 

Ahmed SM, Salgia R (2007). “Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer”. Respirology 11 (6): 68792. doi:10.1111/j.1440-1843.2006.00887.x. PMID 17052295. 

Zhang X, Chang A (2007). “Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer”. J. Med. Genet. 44 (3): 16672. doi:10.1136/jmg.2006.046102. PMID 17158592. 

Cohenuram M, Saif MW (2007). “Epidermal growth factor receptor inhibition strategies in pancreatic cancer: past, present and the future”. JOP 8 (1): 415. PMID 17228128. 

Mellinghoff IK, Cloughesy TF, Mischel PS (2007). “PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors”. Clin. Cancer Res. 13 (2 Pt 1): 37881. doi:10.1158/1078-0432.CCR-06-1992. PMID 17255257. 

Nakamura JL (2007). “The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications”. Expert Opin. Ther. Targets 11 (4): 46372. doi:10.1517/14728222.11.4.463. PMID 17373877. 

v  d  e

PDB Gallery

1ivo: Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains.  

1m14: Tyrosine Kinase Domain from Epidermal Growth Factor Receptor  

1m17: Epidermal Growth Factor Receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib  

1mox: Crystal Structure of Human Epidermal Growth Factor Receptor (residues 1-501) in complex with TGF-alpha  

1nql: Structure of the extracellular domain of human epidermal growth factor (EGF) receptor in an inactive (low pH) complex with EGF.  

1xkk: EGFR kinase domain complexed with a quinazoline inhibitor- GW572016  

1yy9: Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225  

1z9i: A Structural Model for the Membrane-Bound Form of the Juxtamembrane Domain of the Epidermal Growth Factor Receptor  

2gs2: Crystal Structure of the active EGFR kinase domain  

2gs6: Crystal Structure of the active EGFR kinase domain in complex with an ATP analog-peptide conjugate  

2gs7: Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP  

2itn: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AMP-PNP  

2ito: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH IRESSA  

2itp: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788  

2itq: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AFN941  

2itt: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH AEE788  

2itu: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH AFN941  

2itv: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH AMP-PNP  

2itw: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AFN941  

2itx: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AMP-PNP  

2ity: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH IRESSA  

2itz: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH IRESSA  

2j5e: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 13-JAB  

2j5f: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB  

2j6m: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AEE788  

v  d  e

Protein kinases: tyrosine kinases (EC 2.7.10)

 

Receptor tyrosine kinases (EC 2.7.10.1)

EGF receptor family

EGFR  ERBB2  ERBB3  ERBB4

Insulin receptor family

IGF1R  INSR  INSRR

PDGF receptor family

CSF1R  FLT3  KIT  PDGFR (PDGFRA, PDGFRB)

FGF receptor family

FGFR1  FGFR2  FGFR3  FGFR4

VEGF receptors family

VEGFR1  VEGFR2  VEGFR3  VEGFR4

HGF receptor family

MET  RON

Trk receptor family

NTRK1  NTRK2  NTRK3

EPH receptor family

EPHA1  EPHA2  EPHA3  EPHA4  EPHA5  EPHA6  EPHA7  EPHA8  EPHB1  EPHB2  EPHB3  EPHB4  EPHB5  EPHB6  EPHX

LTK receptor family

LTK  ALK

TIE receptor family

TIE  TEK

ROR receptor family

ROR1  ROR2

DDR receptor family

DDR1  DDR2

PTK7 receptor family

PTK7

RYK receptor family

RYK

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AATYK  AATYK2  AATYK3

AXL receptor family

AXL  MER  TYRO3

RET receptor family

RET

uncatagorised

STYK1

 

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family

ABL1  ARG

ACK family

ACK1  TNK1

CSK family

CSK  MATK

FAK family

FAK  PYK2

FES family

FES  FER

FRK family

FRK  BRK  SRMS

JAK family

JAK1  JAK2  JAK3  TYK2

SRC-A family

SRC  FGR  FYN  YES1

SRC-B family

BLK  HCK  LCK  LYN

TEC family

TEC  BMX  BTK  ITK  TXK

SYK family

SYK  ZAP70

v  d  e

Neoplasm: Oncogenes/Proto-oncogenes

Extracellular/

Growth factor

c-Sis/PDGF

Cell membrane/

receptor/tyrosine kinases

ErbB/c-ErbB (HER2/neu, Her 3) – c-Kit – c-Met – c-Ret – Flt3

Cytoplasm/

Signal transduction

c-Src

MAPK/ERK pathway (c-Ras/HRAS, c-Raf)

Akt/PKB signaling pathway (c-Akt)

Wnt signaling pathway (Beta-catenin)

Nucleus/Transcription factors

AP-1 (c-Fos, c-Jun) – c-Myc – c-Mdm2

Other/ungrouped

c-Bcl-2 – Notch – Stathmin

see also tumor suppressor genes

v  d  e

Receptors: growth factor receptors

Nerve growth factors

Low affinity/p75 – high affinity Trk (TrkA, TrkB, TrkC) – Ciliary neurotrophic factor

Somatomedin

Insulin-like growth factor 1 – Insulin-like growth factor 2

CSF

Stem cell factor – Erythropoietin

TGF pathway

TGF-beta (1, 2) – Activin (1, 2) – Bone morphogenetic protein (1, 2)

Other

Hepatocyte growth factor – ErbB/Epidermal growth factor – Fibroblast growth factor (1, 2, 3, 4) – Platelet-derived growth factor (A, B) – VEGF (1, 2, 3)

see also growth factors

Categories: Human proteins | Tyrosine kinase receptors | OncogenesHidden categories: All articles with unsourced statements | Articles with unsourced statements from October 2009 | Articles with unsourced statements from December 2009

There is something captivating about the Mid-Atlantic Region of our country. Perhaps it is the pilgrim, colonial and revolutionary history that took place there. Or maybe it has something to do with so many of our ancestors pouring ashore through the gates of Ellis Island. For me the greenness, rivers, beauty and antiquity of the place are the most attractive qualities of the Mid-Atlantic Region.

One of the most popular Mid-Atlantic states is New Jersey. Situated between New York City and Philadelphia, New Jersey is a popular home for many of the people who work in these two large cities. In addition to the metropolitan attractions and entertainment in the area, residents enjoy the nearby mountains, pine forests, waterfalls, lakes and Atlantic coastline which provide a lot of geographical diversity and outdoor recreation opportunities. Some people are also drawn there because of the ethnic diversity throughout the state.

With so many people living in the state, there is definitely a large selection of real estate in NJ to choose from including apartments, town homes, family homes, open lots and commercial property, but the high demand the area enjoys makes it an expensive place to settle. For example, the median price of homes in New Jersey is about 0,000; which is almost double the national average. There are also more affordable houses for sale if you look in the right places but, on the whole, New Jersey is an expensive place to live. If you can’t afford to buy a house, renting may be an attractive alternative.

The sheer number of real estate options in the area can also make house hunting in New Jersey a difficult task. Consequently, it would be very helpful to have a trustworthy realtor to help you find the right neighborhood, price range and home to meet your needs. With their help you can save time and money during your search. Fortunately, New Jersey has some of the best school systems in the country, so you won’t have to worry too much about which school district your children attend, but a realtor will still have a lot of good insider information that can help you narrow down your search.

A realtor can also help you find good deals, negotiate house prices and close on your new home. With something as expensive as real estate in NJ, you want to make sure everything goes smoothly and is legally secure.

In today’s market it is very important good realtor to represent you. A marketplace full with opportunity, Tax benefits and unpredictable values, proven experience, integrity, market awareness and outstanding communication skills are essential. No one should compromise these qualities. Home Purchases and sales are too important to place in the supervision of inexperienced, unverified realtors.

Whether dealing with a commercial or residential Real estate transaction, the client should verify that the realtor is a affiliate in good standing with the National Association of Realtors (NAR). This membership assures the client of the realtor’s obligation to educational programs and compliance with principles of ethical conduct and cooperation. The National Association of Realtors has been instrumental in increasing and implementing great ethical principles of conduct throughout the industry.

In addition to enrollment with the NAR, the realtor that can best locate and list for sale either residential or commercial Real estate will be a An affiliate of a Multiple Listing Service (MLS). The MLS is a regional marketplace that is designed to assure clients of greatest exposure to existing Real estate and the cooperation of many other real estate Firms. Whether buying or selling, clients be supposed to persist that the realtor be a member of the Multiple listing service in your area.

It is valuable to recognize that the term realtor refers to the agency itself. Realtors, or real estate brokers, hold on to agents that list, sell and lease real estate, on behalf of the realtor. However, the realtor is liable for the activity and conduct of its agents, the Firm’s marketing strategy and the interaction with other cooperating Real estate companies. Selecting a proven and reliable realtor can maximize the sale of a real estate property and assure the buyer of making an informed choice.

Real estate marketing has changed dramatically in the past few years. The industry has been impacted by the advent of enhanced MLS services that have made properties accessible for review on the internet. A recent survey showed that almost 70% of residential Home purchasers began their search Online. In today’s Market, the finest realtors have fine-tuned internet strategies, marketing plans and communication programs that keep their agents, their listings and their clients abreast of activity as it occurs.

Programs such as virtual tours and digital photography can do much to enhance the visibility of listings and can be Changed with the availability of aerial photographs, tax documents and copies of deeds and disclosure statements. Good realtors are capitalizing on the public’s ask for internet access by creating web logs for listings, agents and related projects.

As essential as the internet is to overall real estate marketing, it is imperative to go for a realtor with outstanding communication capabilities. There is no reason for a realtor to avoid a call or be ignorant of market activity as it happens. The greatest Real estate agents understand the importance of being on top of the market at all times and are always accessible to their Buyers and sellers. With the cellphones systems, Clients will benefit from a relationship with a Real estate agent who is always at the Prepered.

Traditional real estate marketing activities, like signs, brochures, flyers, business cards and even Open Houses still have value in the marketplace. Respectable realtors incorporate these principles with Buidling websites and advertising online to boost exposure and facilitate the purchase and sale process.

Realtors need to know the current mortgage market as well.. Many of the greatest Real estate agents have direct lines of access to Banks and programs. In today’s marketplace, clients should examine the realtor’s understanding and relations to the financing arm of the industry. A realtor’s ability to connect Home buyers and the sellers to suitable financing can have a big effect on a property’s marketability and can help bring transactions together easily.

Finally we are able to pull stats that are current on what is really happening in the marketplace. However I would look at these with caution as many of these closings and pendings are because of the expiry of Tax Credit at the end of April and I’m sure Junes closings will reflect that activity as well. As long as the property closed by the end of June and the contract was written and approved by the end of April, the tax credit was still applicable. They don’t allow a category for the short sales which have doubled in closings since a year ago and make up a considerable percent of the available properties for sale. As a Phoenix, Scottsdale realtor, all these figures are what makes our world go round.

 

All Stats were provided by ARMLS and permission was granted to reproduce

May 2010

SALES Month over Month

Housing sales continued strong in April with the closing of 9,306 residential transactions,

up over 3% from the 8,990 units sold in March. Nationally, housing sales fell fractionally

for the same period.

SALES Year over Year

The April numbers were 3.5% higher than April-09 when 8,475 houses sold. This pace far exceeds the national picture which showed only a 2% gain, according to the latest

numbers published by the National Association of REALTORS®.

1

Active Inventory

13,871 new residential listings were added to the ARMLS system in April, a 25% increase over the same month last year when 11,118 were listed.

However Active inventory added to the system was down 5% from the previous month,

continuing a seesaw pattern of ups and downs evident over the past six months. On an

annualized basis, inventory in the most recent twelve months is down 5% from 158,000

to 149,000 homes for sale, slightly ahead of calendar year 2009 when 147,000 homes

were listed.

List Prices

Asking prices on new listings continued steady at 2,250 as the average and 9,900 as the median price. (The median price is the range midpoint where there are as many listed houses above as below it.) The divergence between monthly average and monthly median continues to narrow. This indicates optimism from sellers who have been waiting on the side lines to put their more expensive houses on the market to test the waters. In January, the average list price was nearly 65% higher than the median. In April, that difference was down to 51% continuing a downward slide trend that we have seen for the past four months.

Sale Prices

Closed sales continued to show signs of recovery, with the Average sale price of a single-family home in the Valley falling by about ,000 to 1,200, down from 8,200 in March. However, the good news is that April’s average was over 7% higher than the previous year average price of 9,700. This continues the three month trend of year over year price increases substantiating that the market is starting to stabilize and improve.

The ARMLS Pending Price Index™

The ARMLS PPI™ predicts future average and median prices based on reports of

contracts executed but not yet closed. The ARMLS Pending Price Index is available

only through the ARMLS system and has shown to be a strong indicator of future pricing

trends.

The average price is predicted to rise in May and June, then settle back in July only to

start upward again in August. Year over year, this is a continuing indicator that the

short term market remains fairly steady but still uncertain. The market, driven by first

time and move-up home buyer tax credits that expired in April, will no longer be

bolstered by those incentives. For the summer, all bets are off as the spring market

ends, the snow birds leave for cooler climates, and the summer doldrums set in.

The ARMLS PPI for Median prices likewise shows erratic behavior, ticking upward

fractionally in May, then falling back in each of the next three months. This would

indicate continued activity in the lower price ranges of the market as bank foreclosures

continue to dominate the sale picture.

Foreclosures

The foreclosure inventory continues to plague the resale market by saturating the MLS

with bank owned properties offered at below market rates. The average asking prices for

new listings dropped in April to 2,200, down ,000 from the previous month.

Currently 5,029 or 12.3% of the 47,836 active listings in the ARMLS system are bank

owned/foreclosures. However, in the previous month of April, 3,538 of the 9,306 closed

sales were foreclosures. With 38% of the closings being bank owned foreclosures, the

downward pressure on prices is formidable. ARMLS expects this trend to continue until

the economy begins to recover and unemployment abates.

In the Pending Listing class, 4,760 of the 14,855 of pending listings, or 32%, are bank

owned properties.

For the eighth straight month, the number of pending foreclosures has hovered within 1%

either side of 50,000, according to the Cromford Associates LLC, the market research

affiliate of ARMLS. As they have since August, 2009, banks continue to file foreclosure

notices of trustees sales at a rate of 200-250 per day, a trend that is not expected to

change for quite some time.

Market Time

All of this activity has its effect on market time. The average days on market of a sold

property in April was 97 days, down four days from the previous month. But this is down

from a high of 135 days the market experienced just two years ago in May 2008. Homes

now are selling on average 25% faster than they were just twenty-four months ago.

Commentary

The most recent 12 months show record sales, with March and April leading the charge.

Active inventory added to the market continues downward, putting positive pressure on

supply and demand, a necessity if prices are going to rise.

The housing market continues to try to make a meaningful recovery, but is hampered by

continuing unemployment and economic uncertainty on the national level. ARMLS is

seeing mixed signals from month to month since last October, but positive gains are

mixed with losses. This is a classic pattern that markets make in gaining traction toward

recovery.

ARMLS continues to see glimmers of hope, but no long term, reliable indicators that the

market recovery is imminent. We continue to be hopeful, but must at the same time

remain objective and realistic. This recovery is going to take a long time to develop and

probably won’t mean a normal housing market will return for at least two or three more

years.

© 2010 ARMLS, may be reprinted with proper attribution.

ARMLS STAT MAY 2010

 

Maureen Karpinski

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Finding a good house for living nowadays is pretty difficult, a person has to face several problems to find the perfect house which can suite him or her. With the steady increase of population, the need for houses has increased a lot. People, who used to live in small houses previously, have to shift to bigger ones when their family members increase. Such situations are faced by almost every living person in the world. Due to this, the need for houses has increased at a large extent. Problems exist even when a person finds a new house to live in. The price, condition of the house causes a lot of problems. To get rid of such problems, what people need to do is search for a real estate broker or realtor, who can provide them with the perfect house and at reasonable price. However, it is also pretty difficult to find a good real estate broker.

People of Colorado are lucky in this case; they have got one of the best realtors of United States operating at that region. Andre Mazur, the boulder realtor of Colorado has proved to be one of the best with the excellent services he provides to the people who want to buy or sell houses in that region. A real estate broker is a person who acts as an intermediary between the buyer and seller of a house. The main work of a realtor is to buy a house from a person and then sell it to another one. Most realtors have got huge number of houses in their list. So, if a person wants to buy a house, he or she must contact a good real estate broker. This boulder Colorado realtor has got a long list of houses of varying price ranges. And most of these houses are provided at reasonable price according to the quality and condition of the house.

Even when a person wants to sell his old house for shifting to a new one, he can contact this boulder realtor to serve him. It is often very problematic to find a customer and get a good price for a house, if a person wants to do it by himself. But, if the person leaves this responsibility on a good real estate broker like this boulder Colorado realtor, then he may not have to face such problems. The real estate broker will find a customer for that particular house and help the person to sell it. Since, this transaction of houses involves a lot of money; people always look for a trustworthy real estate broker. A fraud real estate broker can fix up a person and take away his house. But, when you contact this boulder realtor, you should not keep any such queries in mind. He has served people for 13 long years; such a long time of work describes his trustworthiness to the people and also the people’s love towards him. If you are from Colorado or want to buy a house in there, you should contact this boulder realtor to serve your purpose.