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Tuesday, September 15, 2009
Conatct 4 Mesothelioma
for more details about Methelioma - A Cancer disease visit www.mesothelioma.com
Types of Mesothelioma
What are the different types of mesothelioma?
Pleural Mesothelioma – affects the chest and lungs
Malignant pleural mesothelioma often originates within the chest cavity and can, at times, involve the lung. This particular form of mesothelioma can metastasize to numerous organs in the body – even the brain - and tends to do so more frequently than not.
Pleural mesothelioma is not always easily detectable. Frequently, in the early stages of the disease, symptoms may be mild. Patients usually report pain in one area of the chest that never seems to go away, weight loss and fever. Occasionally, other symptoms are more severe and include problems with breathing due to fluid build up in the chest. A CT Scan of the chest area has proven to be the best test for identifying how far along the disease has progressed.
Frequently serum markers are used to diagnose of various forms of cancer. Mesothelioma cannot be diagnosed using this method as no serum markers currently exist. If high levels of hyaluronic acid are present it may be possible to distinguish mesothelioma from other types of cancer or to determine the effectiveness of a treatment protocol.
The survival rate for patients diagnosed with pleural mesothelioma typically is not high. Patients typically do not live beyond seventeen months from the onset of symptoms. Only 8% of those diagnosed with mesothelioma will live three to five years from the onset of symptoms.
Pericardial Mesothelioma – affects the heart
Pericardial mesothelioma is the least common form of mesothelioma. Pericardial mesothelioma, as the name suggests, involves the heart. This rare type of mesothelioma invades the pericardium, the sac that surrounds the heart. As the cancer progresses, the heart is not able to deliver oxygen as efficiently to the body causing further decline in health at an increasingly rapid rate. The symptoms most commonly associated with pericardial mesothelioma mimic those of a heart attack: nausea, pain in the chest and shortness of breath.
Peritoneal Mesothelioma – affects the abdomen
Peritoneal mesothelioma originates in the abdomen and will frequently spread to other organs in area including the liver, spleen or bowel. Severe abdominal pain is the most common complaint that patients present to their doctor. There may also be a discomfort level with fluid build up in the abdomen as well. Other symptoms of peritoneal mesothelioma may include difficult bowel movements, nausea and vomiting, fever and swollen feet.
The survival rate is even worse for those diagnosed with peritoneal mesothelioma will patients typically surviving only ten months from time that they first started experiencing the symptoms noted above.
Malignant Mesothelioma
Malignant mesothelioma is an uncommon form of cancer and of all asbestos related diseases, the most serious. The symptoms associated with the disease make it difficult for doctors to diagnose. Often, by the time that a proper diagnosis is made, the disease has progressed to a point where patients do not respond well to treatment therapy. Malignant mesothelioma is caused almost exclusively by the inhalation of airborne asbestos particles. Another unique factor associated with the disease is that there can be a long latency period between the time an individual is exposed to asbestos and the actual manifestation of the disease in the form of malignant mesothelioma.
Benign Mesothelioma – affects the peritoneum
Cystic mesothelioma primarily affects women of younger age and affects the peritoneum. This type of mesothelioma is not frequently diagnosed and is also not a malignant form of the disease. It is, however, extremely difficult to identify and requires specialized microscopes and immunologic techniques to aid in diagnosis.
Mesothelioma in Uncommon Sites
A form of cardiac cancer that is rarely seen involves the pericardium. Tumors associated with this type of mesothelioma are not easily detectable and patients presented with this diagnosis tend to have a very low survival rate. There have also been reports of mesothelioma involving ovaries in women and the scrotum in men. Treatment for all of these rare forms of mesothelioma will vary depending on what stage a patient has progressed to but in most all cases the projected outcome is not favorable.
Saturday, September 12, 2009
History of Meshothelioma
The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. It was not until 1960 that an article published by Wagner et al. first officially established mesothelioma as a disease arising from exposure to crocidolite asbestos.[31] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. However prior to 1950 malignant mesothelioma was extremely rare and some experts even questioned its existence.[32] In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[33] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.
In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.
Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.
By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.
In Armley, Leeds, England the J W Roberts asbestos incident involved several court cases against Turner & Newall where local residents who contracted mesothelioma claimed compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.[34]
In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.
Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.
By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.
In Armley, Leeds, England the J W Roberts asbestos incident involved several court cases against Turner & Newall where local residents who contracted mesothelioma claimed compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.[34]
Legal Issues realted mesothelioma
The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[29] The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.[30]
Notable people who have lived for some time with mesothelioma
Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote the "The Median Isn't the Message"[27] for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another twenty years eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma. Author Paul Kraus was diagnosed with peritoneal mesothelioma in July 1997. He was given a prognosis of less than a year to live and used a variety of complementary modalities. He continues to outlive his prognosis and wrote a book about his experience "Surviving Mesothelioma and Other Cancers: A Patient's Guide" [28] in which he presented his philosophy about healing and the decision making that led him to use integrative medicine.
Notable people who died from mesothelioma
Mesothelioma, though rare, has had a number of notable patients. Hamilton Jordan, Chief of Staff for President Jimmy Carter and life long cancer activist, died in 2008. Australian anti-racism activist Bob Bellear died in 2005. British science fiction writer Michael G. Coney, responsible for nearly 100 works also died in 2005. American film and television actor Paul Gleason, perhaps best known for his portrayal of Principal Richard Vernon in the 1985 film The Breakfast Club, died in 2006. Mickie Most, an English record producer, died of mesothelioma in 2003. Paul Rudolph, an American architect known for his cubist building designs, died in 1997.
Bernie Banton was an Australian workers' rights activist, who fought a long battle for compensation from James Hardie after he contracted mesothelioma after working for that company. He claimed James Hardie knew of the dangers of asbestos before he began work with the substance making insulation for power stations. Mesothelioma eventually took his life along with his brothers and hundreds of James Hardie workers. James Hardie made an undisclosed settlement with Banton only when his mesothelioma had reached its final stages and he was expected to have no more than 48hrs to live. Australian Prime Minister Kevin Rudd mentioned Banton's extended struggle in his acceptance speech after winning the 2007 Australian Federal Election.
Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen sought alternative treatments from clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the U.S. Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or from its use as an insulating material in car racing suits.[22] (It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos.[citation needed])
United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder is awarded yearly by his wife at the MARF Symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.
After a long period of untreated illness and pain, rock and roll musician and songwriter Warren Zevon was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind including the song "Keep Me in Your Heart," which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003.
Christie Hennessy, the influential Irish singer-songwriter, died of mesothelioma in 2007, and had stridently refused to accept the prognosis in the weeks before his death.[23] His mesothelioma has been attributed to his younger years spent working on building sites in London.[24][25]
Bob Miner, one of the founders of Software Development Labs, the forerunner of Oracle Corporation died of mesothelioma in 1994.
Scottish Labour MP John William MacDougall died of mesothelioma on August 13, 2008, after fighting the disease for two years.[26]
Canberra journalist and news presenter, Peter Leonard also succumbed to the condition on 23 September 2008.
Terrence McCann Olympic gold medalist and longtime Executive Director of Toastmasters, died of mesothelioma on June 7, 2006 at his home in Dana Point, California.
Bernie Banton was an Australian workers' rights activist, who fought a long battle for compensation from James Hardie after he contracted mesothelioma after working for that company. He claimed James Hardie knew of the dangers of asbestos before he began work with the substance making insulation for power stations. Mesothelioma eventually took his life along with his brothers and hundreds of James Hardie workers. James Hardie made an undisclosed settlement with Banton only when his mesothelioma had reached its final stages and he was expected to have no more than 48hrs to live. Australian Prime Minister Kevin Rudd mentioned Banton's extended struggle in his acceptance speech after winning the 2007 Australian Federal Election.
Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen sought alternative treatments from clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the U.S. Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or from its use as an insulating material in car racing suits.[22] (It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos.[citation needed])
United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder is awarded yearly by his wife at the MARF Symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.
After a long period of untreated illness and pain, rock and roll musician and songwriter Warren Zevon was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind including the song "Keep Me in Your Heart," which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003.
Christie Hennessy, the influential Irish singer-songwriter, died of mesothelioma in 2007, and had stridently refused to accept the prognosis in the weeks before his death.[23] His mesothelioma has been attributed to his younger years spent working on building sites in London.[24][25]
Bob Miner, one of the founders of Software Development Labs, the forerunner of Oracle Corporation died of mesothelioma in 1994.
Scottish Labour MP John William MacDougall died of mesothelioma on August 13, 2008, after fighting the disease for two years.[26]
Canberra journalist and news presenter, Peter Leonard also succumbed to the condition on 23 September 2008.
Terrence McCann Olympic gold medalist and longtime Executive Director of Toastmasters, died of mesothelioma on June 7, 2006 at his home in Dana Point, California.
Treatment o mesothelioma
Treatment of malignant mesothelioma using conventional therapies in combination with radiation and or chemotherapy on stage I or II Mesothelioma have proved on average 74.6 percent successful in extending the patient's life span by five years or more [commonly known as remission][this percentage may increase or decrease depending on date of discovery / stage of malignant development] (Oncology Today, 2009). Treatment course is primarily determined by the staging or development. This is unlike traditional treatment such as surgery by itself which has proved only be 16.3 percent likely to extend a patient's life span by five years or more [commonly known as remission]. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.
Surgery
Surgery, by itself, has proved disappointing. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008) A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.
Radiation
Wikibooks has a book on the topic of
Radiation Oncology/Lung/Mesothelioma
For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston.[18] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.
Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy) in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[19] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the combination pemetrexed group in patients who received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[20]
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.
Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[21] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained.
This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.
Surgery
Surgery, by itself, has proved disappointing. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008) A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.
Radiation
Wikibooks has a book on the topic of
Radiation Oncology/Lung/Mesothelioma
For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston.[18] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.
Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy) in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[19] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the combination pemetrexed group in patients who received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[20]
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.
Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[21] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained.
This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.
Epidemiology of mesothelioma
Incidence
Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate is approximately one per 1,000,000. The highest incidence is found in Britain, Australia and Belgium: 30 per 1,000,000 per year.[10] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[11] It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.
Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[12] Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.
Risk factors
Working with asbestos is the major risk factor for mesothelioma.[13] A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.
Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.
The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma.
Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[14]
Exposure
Asbestos was known in antiquity, but it wasn't mined and widely used commercially until the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace, and created guidelines for engineering controls and respirators, protective clothing, exposure monitoring, hygiene facilities and practices, warning signs, labeling, recordkeeping, and medical exams. By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE does not assume that any such threshold exists. People who work with asbestos wear personal protective equipment to lower their risk of exposure.
Environmental exposures
Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos, however, recently, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.[15][16]
Occupational
Exposure to asbestos fibres has been recognized as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.
The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.
Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
Paraoccupational secondary exposure
Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases.[17] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.
Asbestos in buildings
Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.
Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate is approximately one per 1,000,000. The highest incidence is found in Britain, Australia and Belgium: 30 per 1,000,000 per year.[10] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[11] It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.
Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[12] Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.
Risk factors
Working with asbestos is the major risk factor for mesothelioma.[13] A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.
Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.
The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma.
Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[14]
Exposure
Asbestos was known in antiquity, but it wasn't mined and widely used commercially until the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace, and created guidelines for engineering controls and respirators, protective clothing, exposure monitoring, hygiene facilities and practices, warning signs, labeling, recordkeeping, and medical exams. By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE does not assume that any such threshold exists. People who work with asbestos wear personal protective equipment to lower their risk of exposure.
Environmental exposures
Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos, however, recently, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.[15][16]
Occupational
Exposure to asbestos fibres has been recognized as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.
The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.
Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
Paraoccupational secondary exposure
Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases.[17] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.
Asbestos in buildings
Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.
Pathophysiology of mesothelium
The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.
Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[8] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.[9]
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:
Neurofibromatosis type 2 at 22q12
P16INK4A
P14ARF
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
Inactivation of tumor suppressor genes
Activation of oncogenes
Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
Activation of DNA repair enzymes, which may be prone to error
Activation of telomerase
Prevention of apoptosis
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.
Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.
Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[8] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.[9]
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:
Neurofibromatosis type 2 at 22q12
P16INK4A
P14ARF
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
Inactivation of tumor suppressor genes
Activation of oncogenes
Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
Activation of DNA repair enzymes, which may be prone to error
Activation of telomerase
Prevention of apoptosis
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.
Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.
Screening & Staging
Screening
There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[4] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[5]
[edit] Staging
Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[6] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.[6][7]
There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[4] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[5]
[edit] Staging
Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[6] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.[6][7]
Diagnosing mesothelioma
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure).
If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.
If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
Typical immunohistochemistry results
Positive
Negative
EMA (epithelial membrane antigen) in a membranous distribution
CEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1)
B72.3
Calretinin
MOC-3 1
Mesothelin-1
CD15
Cytokeratin 5/6
Ber-EP4
HBME-1 (human mesothelial cell 1)
TTF-1 (thyroid transcription factor-1)
If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.
If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
Typical immunohistochemistry results
Positive
Negative
EMA (epithelial membrane antigen) in a membranous distribution
CEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1)
B72.3
Calretinin
MOC-3 1
Mesothelin-1
CD15
Cytokeratin 5/6
Ber-EP4
HBME-1 (human mesothelial cell 1)
TTF-1 (thyroid transcription factor-1)
Thursday, August 6, 2009
Laptop Data Recovery
Benefits
Full disk encryption has several benefits compared to regular file or folder encryption, or encrypted vaults. The following are some benefits of full disk encryption:
Nearly everything including the swap space and the temporary files is encrypted. Encrypting these files is important, as they can reveal important confidential data. With a software implementation, the bootstrapping code cannot be encrypted however. (For example, Bitlocker leaves an unencrypted volume to boot from, while the volume containing the operating system is fully encrypted.)
With full disk encryption, the decision of which individual files to encrypt is not left up to users' discretion. This is important for situations in which users might not want or might forget to encrypt sensitive files.
Support for pre-boot authentication. [1]
Immediate data destruction, as simply destroying the cryptography keys renders the contained data useless. However, if security towards future attacks is a concern, purging or physical destruction is advised.
Full disk encryption vs. filesystem-level encryption
Full disk encryption does not replace file or directory encryption in all situations. Disk encryption is sometimes used in conjunction with filesystem-level encryption with the intention of providing a more secure implementation. Since disk encryption generally uses the same key for encrypting the whole volume, all data are decryptable when the system runs. However, some FDE solutions use multiple keys for encrypting different partitions. If an attacker gains access to the computer at run-time, he has access to all files. Conventional file and folder encryption instead allows different keys for different portions of the disk. Thus an attacker cannot extract information from still-encrypted files and folders.
Unlike full disk encryption, filesystem-level encryption does not typically encrypt filesystem metadata, such as the directory structure, file names, modification timestamps or sizes.
Full disk encryption and Trusted Platform Module
Trusted Platform Module (TPM) is a secure cryptoprocessor embedded in the motherboard that can be used to authenticate a hardware device. Since each TPM chip is unique to a particular device, it is capable of performing platform authentication. It can be used to verify that the system seeking the access is the expected system.
A limited number of full disk encryption solutions have support for TPM. These implementations can wrap the decryption key using the TPM, thus tying the hard disk drive (HDD) to a particular device. If the HDD is removed from that particular device and placed in another, the decryption process will fail. Recovery is possible with the decryption password or token.
Although this has the advantage that the disk cannot be removed from the device, it might create a single point of failure in the encryption. For example, if something happens to the TPM or the motherboard, you might not be able to access your data simply by connecting the hard drive to another computer, unless you also have a separate recovery key.
Implementations
Main article: Comparison of disk encryption software
There are multiple tools available in the market that allow for full disk encryption. However, they vary greatly in features and security. They are divided into two main categories: hardware-based and software-based. The Hardware-based Full Disk Encryption solutions are considerably faster than the software-based solutions, and usually produce no overhead for the CPU or the hard disk drive. Hardware-based Full Disk Encryption, without some form of user authentication, provides absolutely no protection of data. Currently, there are two solutions providing Pre-Boot Authentication for Hardware-based Full Disk Encryption and a BIOS or ATA password can provide basic access control.
A limited number of full disk encryption solutions also support TPM to tie encrypted data to a particular platform.
Microsoft Windows Vista and Windows Server 2008 include a form of full disk encryption by the name of BitLocker Drive Encryption that can utilize TPM
Full disk encryption has several benefits compared to regular file or folder encryption, or encrypted vaults. The following are some benefits of full disk encryption:
Nearly everything including the swap space and the temporary files is encrypted. Encrypting these files is important, as they can reveal important confidential data. With a software implementation, the bootstrapping code cannot be encrypted however. (For example, Bitlocker leaves an unencrypted volume to boot from, while the volume containing the operating system is fully encrypted.)
With full disk encryption, the decision of which individual files to encrypt is not left up to users' discretion. This is important for situations in which users might not want or might forget to encrypt sensitive files.
Support for pre-boot authentication. [1]
Immediate data destruction, as simply destroying the cryptography keys renders the contained data useless. However, if security towards future attacks is a concern, purging or physical destruction is advised.
Full disk encryption vs. filesystem-level encryption
Full disk encryption does not replace file or directory encryption in all situations. Disk encryption is sometimes used in conjunction with filesystem-level encryption with the intention of providing a more secure implementation. Since disk encryption generally uses the same key for encrypting the whole volume, all data are decryptable when the system runs. However, some FDE solutions use multiple keys for encrypting different partitions. If an attacker gains access to the computer at run-time, he has access to all files. Conventional file and folder encryption instead allows different keys for different portions of the disk. Thus an attacker cannot extract information from still-encrypted files and folders.
Unlike full disk encryption, filesystem-level encryption does not typically encrypt filesystem metadata, such as the directory structure, file names, modification timestamps or sizes.
Full disk encryption and Trusted Platform Module
Trusted Platform Module (TPM) is a secure cryptoprocessor embedded in the motherboard that can be used to authenticate a hardware device. Since each TPM chip is unique to a particular device, it is capable of performing platform authentication. It can be used to verify that the system seeking the access is the expected system.
A limited number of full disk encryption solutions have support for TPM. These implementations can wrap the decryption key using the TPM, thus tying the hard disk drive (HDD) to a particular device. If the HDD is removed from that particular device and placed in another, the decryption process will fail. Recovery is possible with the decryption password or token.
Although this has the advantage that the disk cannot be removed from the device, it might create a single point of failure in the encryption. For example, if something happens to the TPM or the motherboard, you might not be able to access your data simply by connecting the hard drive to another computer, unless you also have a separate recovery key.
Implementations
Main article: Comparison of disk encryption software
There are multiple tools available in the market that allow for full disk encryption. However, they vary greatly in features and security. They are divided into two main categories: hardware-based and software-based. The Hardware-based Full Disk Encryption solutions are considerably faster than the software-based solutions, and usually produce no overhead for the CPU or the hard disk drive. Hardware-based Full Disk Encryption, without some form of user authentication, provides absolutely no protection of data. Currently, there are two solutions providing Pre-Boot Authentication for Hardware-based Full Disk Encryption and a BIOS or ATA password can provide basic access control.
A limited number of full disk encryption solutions also support TPM to tie encrypted data to a particular platform.
Microsoft Windows Vista and Windows Server 2008 include a form of full disk encryption by the name of BitLocker Drive Encryption that can utilize TPM
Saturday, August 1, 2009
Mesothelioma - A disease
Mesothelioma is a form of cancer that is almost always caused by exposure to asbestos. In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and internal chest wall), but it may also occur in the peritoneum (the lining of the abdominal cavity), the heart,[1] the pericardium (a sac that surrounds the heart) or tunica vaginalis.
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.[2] Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases risk of other asbestos-induced cancer.[3] Compensation via asbestos funds or lawsuits is an important issue in mesothelioma (see asbestos and the law).
The symptoms of mesothelioma include shortness of breath due to pleural effusion (fluid between the lung and the chest wall) or chest wall pain, and general symptoms such as weight loss. The diagnosis may be suspected with chest X-ray and CT scan, and is confirmed with a biopsy (tissue sample) and microscopic examination. A thoracoscopy (inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc to obliterate the pleural space (called pleurodesis), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy, radiation therapy or sometimes surgery, the disease carries a poor prognosis. Research about screening tests for the early detection of mesothelioma is ongoing.
Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.
Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
Chest wall pain
Pleural effusion, or fluid surrounding the lung
Shortness of breath
Fatigue or anemia
Wheezing, hoarseness, or cough
Blood in the sputum (fluid) coughed up (hemoptysis)
In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.
Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:
Abdominal pain
Ascites, or an abnormal buildup of fluid in the abdomen
A mass in the abdomen
Problems with bowel function
Weight loss
In severe cases of the disease, the following signs and symptoms may be present:
Blood clots in the veins, which may cause thrombophlebitis
Disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
Jaundice, or yellowing of the eyes and skin
Low blood sugar level
Pleural effusion
Pulmonary emboli, or blood clots in the arteries of the lungs
Severe ascites
A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.[2] Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases risk of other asbestos-induced cancer.[3] Compensation via asbestos funds or lawsuits is an important issue in mesothelioma (see asbestos and the law).
The symptoms of mesothelioma include shortness of breath due to pleural effusion (fluid between the lung and the chest wall) or chest wall pain, and general symptoms such as weight loss. The diagnosis may be suspected with chest X-ray and CT scan, and is confirmed with a biopsy (tissue sample) and microscopic examination. A thoracoscopy (inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc to obliterate the pleural space (called pleurodesis), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy, radiation therapy or sometimes surgery, the disease carries a poor prognosis. Research about screening tests for the early detection of mesothelioma is ongoing.
Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.
Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
Chest wall pain
Pleural effusion, or fluid surrounding the lung
Shortness of breath
Fatigue or anemia
Wheezing, hoarseness, or cough
Blood in the sputum (fluid) coughed up (hemoptysis)
In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.
Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:
Abdominal pain
Ascites, or an abnormal buildup of fluid in the abdomen
A mass in the abdomen
Problems with bowel function
Weight loss
In severe cases of the disease, the following signs and symptoms may be present:
Blood clots in the veins, which may cause thrombophlebitis
Disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
Jaundice, or yellowing of the eyes and skin
Low blood sugar level
Pleural effusion
Pulmonary emboli, or blood clots in the arteries of the lungs
Severe ascites
A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.
Wednesday, July 29, 2009
Domain registration
A domain name registry, is a database of all domain names registered in a top-level domain. A registry operator, also called a Network Information Center (NIC), is the part of the Domain Name System (DNS) of the Internet that keeps the database of domain names, and generates the zone files which convert domain names to IP addresses. Each NIC is an organisation that manages the registration of Domain names within the top-level domains for which it is responsible, controls the policies of domain name allocation, and technically operates its top-level domain. It is potentially distinct from a domain name registrar. [1]
Domain names are managed under a hierarchy headed by the Internet Assigned Numbers Authority (IANA), which manages the top of the DNS tree by administrating the data in the root nameservers.
IANA also operates the .int registry for intergovernmental organisations, the .arpa zone for protocol administration purposes, and other critical zones such as root-servers.net.
IANA delegates all other domain name authority to other domain name registries such as VeriSign.
Some name registries are government departments (e.g., the registry for Sri Lanka nic.lk). Some are co-operatives of internet service providers (such as DENIC) or not-for profit companies (such as Nominet UK). Others operate as commercial organizations, such as the US registry (nic.us).
The allocated and assigned domain names are made available by registries by use of the WHOIS system and via their Domain name servers.
Some registries sell the names directly (like SWITCH in Switzerland) and others rely on separate entities to sell them. For example, names in the .com TLD are in some sense sold "wholesale" at a regulated price by VeriSign, and individual domain name registrar sell names "retail" to businesses and consumers.
Domain names are managed under a hierarchy headed by the Internet Assigned Numbers Authority (IANA), which manages the top of the DNS tree by administrating the data in the root nameservers.
IANA also operates the .int registry for intergovernmental organisations, the .arpa zone for protocol administration purposes, and other critical zones such as root-servers.net.
IANA delegates all other domain name authority to other domain name registries such as VeriSign.
Some name registries are government departments (e.g., the registry for Sri Lanka nic.lk). Some are co-operatives of internet service providers (such as DENIC) or not-for profit companies (such as Nominet UK). Others operate as commercial organizations, such as the US registry (nic.us).
The allocated and assigned domain names are made available by registries by use of the WHOIS system and via their Domain name servers.
Some registries sell the names directly (like SWITCH in Switzerland) and others rely on separate entities to sell them. For example, names in the .com TLD are in some sense sold "wholesale" at a regulated price by VeriSign, and individual domain name registrar sell names "retail" to businesses and consumers.
Tuesday, July 14, 2009
European fine sends Intel into the red
Intel reported a net loss of 398 million dollars for the April-June period after being hit with a 1.45-billion-dollar fine in May for allegedly abusing its stranglehold on the semiconductor market to crush its main rival, AMD.
Intel said that excluding the effects of the European Commission fine, it recorded earnings per share of 18 cents for the quarter, better than the eight cents per share expected by Wall Street analysts.
"Intel's second-quarter results reflect improving conditions in the PC market segment with our strongest first- to second-quarter growth since 1988 and a clear expectation for a seasonally stronger second half," Intel president and chief executive Paul Otellini said in a statement.
"Intel's strategy of investing in new technologies and innovative products, combined with ongoing focus on operating efficiencies, continues to yield benefits that are evident in our strengthening financial performance," he said.
Intel reported second-quarter revenue of eight billion dollars -- up from 7.14 billion dollars in the first quarter -- and a net profit of one billion dollars excluding the European Commission fine.
The European Commission, Europe's top competition watchdog, accused Intel of using illegal loyalty rebates to squeeze rivals out of the market for central processing units (CPUs) -- the brains inside personal computers.
The Santa Clara, California-based company dominated the 30-billion-dollar market for the ubiquitous x86 CPUs with a 70-percent share during the more than five years it was accused of breaking EU antitrust rules.
The commission said Intel had used wholly or partially hidden rebates to get PC makers such as Acer, Dell, HP, Lenovo and NEC to buy all or almost all their CPU supplies from Intel instead of US rival Advanced Micro Devices (AMD).
Intel said it expected revenue of 8.5 billion dollars in the current quarter, better than the 7.79 billion dollars forecast by analysts.
It said revenue from its Atom microprocessors and chipsets was 362 million dollars in the April-June period, up 65 percent over the previous quarter.
It said its gross margin was 50.8 percent in the second quarter, higher than expectations and the 45.6 percent in the key indicator recorded in the first quarter.
Intel said it expected an even better gross margin of 53 percent plus or minus two percentage points in the current quarter.
Intel said that excluding the effects of the European Commission fine, it recorded earnings per share of 18 cents for the quarter, better than the eight cents per share expected by Wall Street analysts.
"Intel's second-quarter results reflect improving conditions in the PC market segment with our strongest first- to second-quarter growth since 1988 and a clear expectation for a seasonally stronger second half," Intel president and chief executive Paul Otellini said in a statement.
"Intel's strategy of investing in new technologies and innovative products, combined with ongoing focus on operating efficiencies, continues to yield benefits that are evident in our strengthening financial performance," he said.
Intel reported second-quarter revenue of eight billion dollars -- up from 7.14 billion dollars in the first quarter -- and a net profit of one billion dollars excluding the European Commission fine.
The European Commission, Europe's top competition watchdog, accused Intel of using illegal loyalty rebates to squeeze rivals out of the market for central processing units (CPUs) -- the brains inside personal computers.
The Santa Clara, California-based company dominated the 30-billion-dollar market for the ubiquitous x86 CPUs with a 70-percent share during the more than five years it was accused of breaking EU antitrust rules.
The commission said Intel had used wholly or partially hidden rebates to get PC makers such as Acer, Dell, HP, Lenovo and NEC to buy all or almost all their CPU supplies from Intel instead of US rival Advanced Micro Devices (AMD).
Intel said it expected revenue of 8.5 billion dollars in the current quarter, better than the 7.79 billion dollars forecast by analysts.
It said revenue from its Atom microprocessors and chipsets was 362 million dollars in the April-June period, up 65 percent over the previous quarter.
It said its gross margin was 50.8 percent in the second quarter, higher than expectations and the 45.6 percent in the key indicator recorded in the first quarter.
Intel said it expected an even better gross margin of 53 percent plus or minus two percentage points in the current quarter.
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