AMD Am29000

The AMD 29000, often simply 29k, was a popular family of RISC-based 32-bit microprocessors and microcontrollers from Advanced Micro Devices. They were, for a time, the most popular RISC chips on the market, widely used in laser printers from a variety of manufacturers. In late 1995 AMD dropped development of the 29k because the design team was transferred to support the PC side of the business. What remained of AMD's embedded business was realigned towards the embedded 186 family of 80186 derivatives. The majority of AMD's resources were then concentrated on their high-performance, desktop x86 clones, using many of the ideas and individual parts of the latest 29k to produce the AMD K5.

The 29000 evolved from the same Berkeley RISC design that also led to the Sun SPARC and Intel i960. One "trick" used in all of the Berkeley-derived designs is the concept of register windows, a technique used to speed up procedure calls significantly. The basic idea is to use a large set of registers as a stack, loading local data into a set of registers during a call, and marking them "dead" when the procedure returns. Values being returned from the routines would be placed in the "global page", the top eight registers in the SPARC (for instance). It is interesting to note that the competing early RISC design from Stanford University looked at this concept, but decided that improved compilers could make more efficient use of general purpose registers than a hard-wired window, something that has proven true over the years.

AMD FireStream

The AMD FireStream (previously branded as both ATI FireStream and AMD Stream Processor^[1]) is a stream processor developed by ATI Technologies. It is designed to target various industries, such as the High Performance Computing (HPC), scientific, and financial sectors, which utilize the stream processing/GPGPU (General Purpose Graphics Processing Units) concept for heavy floating-point computations. The AMD FireStream can also be used as a floating-point co-processor for offloading CPU calculations, which is part of the Torrenza initiative.

AMD Live!

AMD LIVE! is the name of Advanced Micro Devices' initiative in 2005 aimed at gathering the support of professional musicians and other media producers behind its hardware products. The primary focus of this initiative was the Opteron server- and workstation-class central processing units (CPUs).

AMD subsequently extended AMD LIVE! into a platform marketing initiative focusing the consumer electronics segment in 2006 and focused on performance segment desktop-class processors. AMD LIVE! for consumer electronics segment was announced on January 4, 2006 officially through press release.

The AMD LIVE! is an initiative, which can be divided into two parts, one in terms of software and the other, computer hardware. The software portion focuses on users' internet and multimedia experiences, while the hardware sector focuses on the ability of a system to handle multimedia files and the convergence of consumer electronics (CE) and personal computing (PC) into one computer chassis.

AMD 700 chipset series

The AMD 700 chipset series (also called as AMD 7-Series Chipsets) is a set of current and upcoming chipsets designed by ATI for AMD Phenom processors to be sold under the AMD brand. Several members were launched in the end of 2007 and the first half of 2008, others are scheduled to launch throughout the rest of 2008.

The existence of the chipsets was proven on October 2006 through two hardware websites in Chile ^[2][3] and Spain ^[4] which posted the leaked slides of an ATI internal event, "ATI chipset update". In the slides, ATI has shown a series of RD700 series chipset logics. Codenamed RD790, RX790, RS780 and RS740 respectively. A codenamed SB700 southbridge was also mentioned in the event. The 790X (codenamed RD780) chipset was spotted in Computex 2007, exhibited by ASUS ^[5], while the SB750 southbridge was reported by VR-Zone ^[6]. The RS780D was first reported by HKEPC ^[7] while the RX780H was first seen on ECS internal presentations. ^[8]

After the acquisition of ATI Technologies, AMD started to participate in the development of the chipset series. And as a result, the first performance and enthusiast segment chipsets products under the AMD brand, The 790FX, 790X and 770 chipsets were launched on November 19, 2007 as part of the Spider codenamed desktop performance platform. The 780 chipset series, first launched in China on January 23, 2008, and released worldwide on March 5, 2008 during CeBIT 2008 ^[9], mobile chipsets (M740G, M780G and M780T chipsets) were released on June 4, 2008 during Computex 2008 as part of the Puma mobile platform and the 790GX chipset was released on August 6, 2008, while some other members are expected to be released at a later date in 2008.

Athlon 64

The Athlon 64 is an eighth-generation, AMD64-architecture microprocessor produced by AMD, released on September 23, 2003.^[1] It is the third processor to bear the name Athlon, and the immediate successor to the Athlon XP.^[2] The second processor (after the Opteron) to implement AMD64 architecture and the first 64-bit processor targeted at the average consumer,^[3] it was AMD's primary consumer microprocessor, and competes primarily with Intel's Pentium 4, especially the "Prescott" and "Cedar Mill" core revisions. It is AMD's first K8, eighth-generation processor core for desktop and mobile computers.^[4] Despite being natively 64-bit, the AMD64 architecture is backward-compatible with 32-bit x86 instructions.^[5] Athlon 64s have been produced for Socket 754, Socket 939, Socket 940, and Socket AM2.

Models

K6 (Model 6)

• 8.8 million transistors in 350 nm
• L1-Cache: 32 + 32 KB (Data + Instructions)
• MMX
• Socket 7
• Front side bus: 66 MHz
• First release: April 2, 1997
• VCore: 2.9 V (166/200) 3.2/3.3 V (233)
• Clockrate: 166, 200, 233 MHz

AMD K6

The K6 microprocessor was launched by AMD in 1997. The main advantage of this particular microprocessor is that it was designed to fit into existing desktop designs for Pentium branded CPUs. It was marketed as a product which could perform as well as its Intel Pentium II equivalent but at a significantly lower price. The K6 had a considerable impact on the PC market and presented Intel with a serious competition

AMD K5

The K5 was AMD's first x86 processor developed entirely in-house, introduced in March 1996.^[1]. Its primary competition was Intel's Pentium microprocessor range. Although it was originally scheduled for launch in 1995, due to design issues, it was delayed until 1996.^[2] AMD as a company was not as mature as Intel regarding microprocessor design, thus a lot of deadlines were missed and there was a lack of manufacturing expertise in scaling designs. The K5 was an ambitious design, closer to a Pentium Pro than a Pentium regarding technical solutions and internal architecture. However, the final product was closer to the Pentium regarding performance.

AMD K10

The AMD K10 is AMD's latest microprocessor architecture. Though there were once reports that the K10 had been cancelled ^[1], the first third-generation Opteron products for servers were launched on September 10, 2007, with the Phenom processors for desktops following and launching on November 11, 2007 as the immediate successors to the K8 series of processors (Athlon 64, Opteron, 64-bit Sempron).

Am486

The Am486 is a 80486-class family of computer processors that was produced by AMD in the 1990s. Intel beat AMD to market by nearly four years, but AMD priced its 40 MHz 486 at or below Intel's price for a 33 MHz chip, offering about 20% better performance for the same price. Early AMD 486 chips were drop-in replacements for their Intel counterparts, but later AMD clock-doubled 486s ran at 3.3 volts instead of Intel's 5 volts, which limited their suitability as upgrade chips until third-party voltage adapters appeared on the market.

While competing 486 chips, such as those from Cyrix, benchmarked lower than the equivalent Intel chip, AMD's 486 matched Intel's performance on a clock-for-clock basis.

While the Am386 was primarily used by small computer manufacturers, the Am486DX, DX2, and SX2 chips gained acceptance among larger computer manufacturers, especially Acer and Compaq, in the 1994 time frame.

AMD's higher clocked 486 chips provided superior performance to many of the early Pentium chips, especially the 60 and 66 MHz launch products. While equivalent Intel 80486DX4 chips were priced high and required a minor socket modification, AMD priced low. Intel's DX4 chips initially had twice the cache of the AMD chips, giving them a slight performance edge, but AMD's DX4-100 usually cost less than Intel's DX2-66.

The enhanced Am486 series supported new features like extended power-saving modes and Write-Back L1-Cache, later versions even got an upgrade to 16 KiB Write-Back L1-Cache.

The 133 MHz AMD Am5x86 was a higher clocked enhanced Am486.

Structured settlement factoring

transaction

A structured settlement factoring transaction describes the selling of future structured settlement payments (or, more accurately, rights to receive the future structured settlement payments). People who receive structured settlement payments (for example, the payment of personal injury damages over time instead of in a lump sum at settlement) may decide at some point that they need more money in the short term than the periodic payment provides over time. People's reasons are varied but can include unforeseen medical expenses for oneself or a dependent, the need for improved housing or transportation, education expenses and the like. To meet this need, the structured settlement recipient can sell (or, less commonly, encumber) all or part of their future periodic payments for a present lump sum.

History

Structured settlements experienced an explosion in use beginning in the 1980s.[1] The growth is most likely attributable to the favorable federal income tax treatment such settlements receive as a result of the 1982 amendment of the tax code to add § 130.[2] [3] Internal Revenue Code § 130 provides, inter alia, substantial tax incentives to insurance companies that establish “qualified” structured settlements.[4] There are other advantages for the original tort defendant (or casualty insurer) in settling for payments over time, in that they benefit from the time value of money (most demonstrable in the fact that an annuity can be purchased to fund the payment of future periodic payments, and the cost of such annuity is far less than the sum total of all payments to be made over time). Finally, the tort plaintiff also benefits in several ways from a structured settlement, notably in the ability to receive the periodic payments from an annuity that gains investment value over the life of the payments, and the settling plaintiff receives the total payments, including that “inside build-up” value, tax-free.[5]

However, a substantial downside to structured settlements comes from their inherent inflexibility.[6] To take advantage of the tax benefits allotted to defendants who choose to settle cases using structured settlements, the periodic payments must be set up to meet basic requirements [set forth in IRC 130(c)]. Among other things, the payments must be fixed and determinable, and cannot be accelerated, deferred, increased or decreased by the recipient.[7] For many structured settlement recipients, the periodic payment stream is their only asset. Therefore, over time and as recipients’ personal situations change in ways unpredicted at the settlement table, demand for liquidity options rises. To offset the liquidity issue, most structured settlement recipients, as a part of their total settlement, will receive an immediate sum to be invested to meet the needs not best addressed through the use of a structured settlement. Beginning in the late 1980s, a few small financial institutions started to meet this demand and offer new flexibility for structured settlement payees.[8]

Process

Pre-2002

Congress enacted law to provide special tax breaks for payments received by tort victims in structured settlements, and for the companies that funded them. The payments were tax free, whereas if the tort victim had been given a lump sum and invested it themselves, the payments from those investments would be taxable.

Companies liked structured settlements because it allowed them to avoid taxes to a certain extent, and plaintiffs liked them because it allowed them to receive tax-free payments of what became, over time, a much larger amount of money than the original amount paid out by the settling party. Such settlements were also considered an especially good idea for minors, as they held the money safe for adulthood and ensured that youth would not find the money wasted or ill-spent. “Despite the best intentions of plaintiffs, lump sum settlement awards are often quickly dissipated because of excessive spending, poor financial management, or a combination of both. Statistics showed that twenty-five to thirty percent of all cash awards are exhausted within two months, and ninety percent are exhausted within five years.” Andrada, “Structured Settlements – The Assignability Problem,” 9 S. Cal. Interdis. L.J. 465, 468 (Spring 2000).

An explanation of IRS Code section 130 was given during discussions of possible taxation of companies that bought future payments under those structured settlements. “By enacting the PPSA, Congress expressed its support of structured settlements, and sought to shield victims and their families from pressures to prematurely dissipate their recoveries.” 145 Cong. Rec. S52281-01 (daily ed. May 13, 1999) (statement of Sen. Chaffee).

Congress was willing to afford such tax advantages based on the belief that the loss in income taxes would be more than made up by lower expenditures on public assistance programs for those who suffered significant injuries. A strict requirement for a structured settlement to qualify for this tax break was that the tort victim was barred from accessing their periodic payments before they came due. It was for this reason that the annuity had to be owned by another who had control over it. The tort victim could not be seen to have “constructive receipt” of the annuity funds prior to their periodic payments. If the tort victim could cash in the annuity at any time, it was possible that the IRS might find constructive receipt.

“Congress conditioned the favorable rules on a requirement that the periodic payments cannot be accelerated, deferred, increased or decreased by the injured person. Both the House Ways and Means and Senate Finance Committee Reports stated that the periodic payments as personal injury damages are still excludable fro income only if the recipient is not in constructive receipt of or does not have the current economic benefit of the sum required to produce the periodic payments.”

Testimony of Tax Legislative Counsel Joseph M. Mikrut to the Subcommittee on Oversight of the Committee of Ways and Means, March 18, 1999. “These factoring transactions directly undermine the policy objective underlying the structured settlement tax regime, that of protecting the long term financial needs of injuries persons . . . “ (Id.)

Mr. Mikrut was testifying in favor of imposing a punitive tax on factoring companies that engaged in pursuit of structured settlement payments. Despite the use of non-assignment clauses in annuity contracts to secure the tax advantages for tort victims. companies cropped up that tried to advantage of these individuals in ”factoring” transactions, purchasing their periodic payments in return for a deeply discounted lump sump payment. Congress felt that factoring company purchases of structured settlement payments “so directly subvert the Congressional policy underlying structured settlements and raise such serious concerns for the injured victims,” that bills were proposed in both the Senate and the House to penalize companies which engage in such transactions. (Id.)

Before the enactment of IRC 5891, which became effective on July 1, 2002, some states regulated the transfer of structured settlement payment rights, while others did not. Most states that regulated transfers at this time followed a general pattern, substantially similar to the present day process which is mandated in IRC 5891 (see below for more details of the post-2002 process). However, the majority of the transfers processed from 1988 to 2002 were not court ordered.[9] After negotiating the terms of the transaction (including the payments to be sold and the price to be paid for those payments), a formal purchase contract was executed, effecting an assignment of the subject payments upon closing. Part of this assignment process also included the grant of a security interest in the structured settlement payments, to secure performance of the seller’s obligations. Filing a public lien based on that security agreement created notice of this assignment and interest. The insurance company issuing the structured settlement annuity checks was typically not given actual notice of the transfer, due to antagonism by the insurance industry against factoring and transfer companies. Many annuity issuers were concerned that factoring transactions, which were not contemplated when Congress enacted IRC 130, might upset the tax treatment of qualified assignments. HR 2884 (discussed below) resolved this question for annuity issuers.

Federal legislation

In January 2002, Congress accepted Mr. Mikrut’s suggestion and changed tax law to make a statement about sales of structured settlement payments. It decided that the IRS would be able to impose a 40% tax on any difference between the value of the future payments sold and the amount paid to the person who wanted to sell. The sole exception was where the sale was approved by a Court under certain conditions. IRS Code section 5891 became effective in July 2002.

In 2001, Congress passed HR 2884, signed into law by the President in 2002 and effective July 1, 2002, codified at Internal Revenue Code § 5891.[10] Through a punitive excise tax penalty, this has created the de facto regulatory paradigm for the factoring industry. In essence, to avoid the excise tax penalty, IRC 5891 requires that all structured settlement factoring transactions be approved by a state court, in accordance with a qualified state statute. Qualified state statutes must make certain baseline findings, including that the transfer is in the best interest of the seller, taking into account the welfare and support of any dependents. In response, many states enacted statutes regulating structured settlement transfers in accord with this mandate.

Post-2002

Today, all transfers are completed through a court order process. As of November 11, 2008, 46 states(Map). have transfer laws in place regulating the transfer process. Of these, 41 are based in whole or in part on the model state law enacted by NCOIL, the National Conference of Insurance Legislators (or, in cases when the state law predates the model act, they are substantially similar).

Most state transfer laws contain similar provisions, as follows: (1) pre-contract disclosures to be made to the seller concerning the essentials of the transaction; (2) notice to certain interested parties; (3) an admonition to seek professional advice concerning the proposed transfer; and (4) court approval of the transfer, including a finding that it is in the best interest of seller, taking into account the welfare and support of any dependents.

Factoring Terminology

Best Interest Standard

Internal Revenue Code Sec. 5891 and most state laws require that a court find that a proposed settlement factoring transaction be in the best interest of the seller, taking into account the welfare and support of any dependents. [11] “Best interest” is generally not defined, which gives judges flexibility to make a subjective determination on a case-by-case basis. Some state laws may require that the judge look at factors such as the “purpose of the intended use of the funds,” the payee’s mental and physical capacity, and the seller’s potential need for future medical treatment. [12] [13]. One Minnesota court described the “best interest standard” as a determination involving “a global consideration of the facts, circumstances, and means of support available to the payee and his or her dependents.” [14]

Courts have consistently found that the “best interest standard” is not limited to financial hardship cases. [15] Hence, a transfer may be in a seller’s best interest because it allows him to take advantage of an opportunity (i.e., buy a new home, start a business, attend college, etc.) or to avoid disaster (i.e., pay for a family member’s unexpected medical care, pay off mounting debt, etc.). For example, a New Jersey court found that a transaction was in a seller’s best interest where the funds were used to “pay off bills…and to buy a home and get married.” [16]

Although sometimes criticized for being vague, the best interest standard’s lack of precise definition allows considerable latitude in judicial review. Courts can consider on a case-by-case basis the totality of the circumstances surrounding the transfer to determine whether it should be approved.

Discount Rate

In the beginning, the factoring industry had some relatively high discount rates due to heavy expenses caused by costly litigation battles and limited access to traditional investors. However, once state and federal legislation was enacted, the industry’s interest rates decreased dramatically. There is much confusion with the terminology “discount rate” because the term is used in different ways. The discount rate referred to in a factoring transaction is similar to an interest rate associated with home loans, credit cards and car loans where the interest rate is applied to the payment stream itself. In a factoring transaction, the factoring company knows the payment stream they are going to purchase and applies an interest rate to the payment stream itself and solves for the funding amount, as though it was a loan. Discount rates from factoring companies to consumers can range anywhere between under 8% up to over 18% but usually average somewhere in the middle (link to a discount rate calculator can be found here). Factoring discount rates can be a bit higher when compared to home loan interest rates, due to the fact the factoring transactions are more of a boutique product for investors opposed to the mainstream collateralized mortgage transactions. One common mistake in calculating the discount rate is to use “elementary school math” where you take the funding/loan amount and divide it by the total price of all the payments being purchased. Because this method disregards the concept of time (and the time value of money), the resulting percentage is useless. For example, the court in In Re Henderson Receivables Origination v. Campos noted an annual discount rate of 16.8% where the annuitant received $36,500 for the assignment of payments totaling $63,364.94 over 84 months (two monthly payments of $672.32 each, beginning September 30, 2006 and ending on October 31, 2006; eighty-two monthly payments of $692.49 each, increasing 3% every twelve months, beginning on November 30, 2006 and ending on August 31, 2013). However, had the court in Henderson Receivables Origination applied the illogical formula of discounting from “elementary school math” ($36,500/ $63,364.94), the discount rate would have been an astronomical (and nonsensical) 61%. [17]

Discounted Present Value

Another term commonly used in factoring transactions is “discounted present value,” which is defined in the NCOIL model transfer act as “the present value of future payments determined by discounting such payments to the present using the most recently published Applicable Federal Rate for determining the present value of an annuity, as issued by the United States Internal Revenue Service.” [18] The IRS discount rate, also known as the Applicable Federal Rate (AFR), is used to determine the charitable deduction for many types of planned gifts, such as charitable remainder trusts and gift annuities. The rate is the annual rate of return that the IRS assumes the gift assets will earn during the gift term. The IRS discount rate is published monthly (link to current rate may be found here). In Henderson Receivables Origination (above), the court calculated the discounted present value of the $63,364.94 to be transferred as $50,933.18 based on the applicable federal rate of 6.00%. [18] The “discounted present value” is a measuring stick for determining what the value of a future payment (i.e., a payment that is due in the year 2057) is today. Hence, the discounted present value of a payment corrects for inflation and the principle that money available today is worth more than money not accessible for 50 years (or some future time). However, the discounted present value is not the same thing as market value (what someone is willing to pay). Basically, a calculation that discounts a future payment based on IRS rates is an artificial number since it has no bearing on the payment’s actual selling price. For example, in Henderson Receivables Origination, it is somewhat confusing for the court to evaluate future payments totaling $63,364,94 based the discounted present value of $50,933.18 because that is not the market value of the payments. In other words, the annuitant couldn’t go out and get $50,933.18 for his future payments because no person or company would be willing to pay that much. Some states will require a quotient to be listed on the disclosure that is sent to the customer prior to entering into a contract with a factoring company. The quotient is calculated by dividing the purchase price by the discounted present value. The quotient (like the discounted present value) provides no relevance in the pricing of a settlement factoring transaction. In Henderson Receivables Origination (above), the court did consider this quotient which was calculated as 71.70% ($36,500/ $50,933.18). [19]

Structured sale

A structured sale is a special type of installment sale pursuant to the Internal Revenue Code.^[1] Installment sales permit sellers to defer recognition of gains on the sale of a business or real estate to the tax year in which the related sale proceeds are received. Structured sales allow the seller of an asset to pay taxes over time while having the payments guaranteed by a high credit quality alternate obligor, who accepts assignment of the buyers periodic payment obligation. Transactions can currently be done as small as $100,000.

In a structured sale, rather than the buyer paying the installments, the buyer pays cash, some of which is used as consideration for a third party assignment company to accept the payment obligation. The assignment company then purchases an annuity from a life insurance company with high financial ratings from A. M. Best. Case law and administrative precedents support recognition of the original contract terms after a substitution of obligors.^[2] In addition, a properly handled transaction will avoid issues with constructive receipt and economic benefit.

While negotiating the installment payments, the seller is free to design payment streams with a great deal of flexibility. Each installment payment to the seller has three components: deferred return of basis, deferred capital gain, and ordinary income earned on the money in the annuity. Under the doctrine of constructive receipt, with a properly documented structured sale, no taxable event is recognized unless a payment is actually received. Taxation is the same as if the buyer were making installment payments directly.

Structured sales are an alternative to a section 1031 exchange, which defers recognition of capital gain, but forces the seller to continue holding some form of property. Structured sales work well for sellers who want to create a continuing stream of income without management worries. Retiring business owners and downsizing homeowners are examples of sellers who can benefit.

The structured sale must be documented, and money must be handled in such a way that the ultimate recipient is not treated as having constructive received the payment prior to the time it is actually paid. For the buyer, there is no difference from a traditional cash-and-title-now deal, except for additional paperwork. Because of tax advantages to the seller, structuring the sale might, however, make the buyer's offer more attractive. Because the buyer has paid in full, the buyer gets full title at time of closing.

There are no direct fees to the buyer or seller to employ the structured sale strategy. The structured settlement specialist who implements the transaction is paid directly by the life insurance company that writes the annuity.

The internal rate of return is comparable to long term high quality debt instruments.

Allstate Life was the originator of the structured sale concept and until recently was the only structured settlement annuity company whose product was available for the structured sale transaction. Prudential has begun to use its non-qualified assignment product on a limited basis.

Mesothelioma Applied Research Foundation

The Mesothelioma Applied Research Foundation (Meso Foundation, formerly MARF) is a non-profit organization that funds mesothelioma research, provides services to patients, educates the public, and advocates in Washington, DC for governmental funding for mesothelioma research. The organization's mission is to eradicate mesothelioma as a life-ending disease.

Mesothelioma is a cancer caused by exposure to asbestos.

To date, the Foundation has funded over $5 million in clinical research and is the host of the annual International Symposium on Malignant Mesothelioma.

Chloracne

Chloracne is an acne-like eruption of blackheads, cysts, and pustules associated with over-exposure to certain halogenated aromatic compounds, such as chlorinated dioxins and dibenzofurans. The lesions are most frequently found on the cheeks, behind the ears, in the armpits and groin region.

The condition was first described in German industrial workers in 1897 by Von Bettman, and was initially believed to be caused by exposure to toxic chlorine (hence the name "chloracne"). It was only in the mid-1950s that chloracne was associated with aromatic hydrocarbons^[1]. The substances that may cause chloracne are now collectively known as chloracnegens.

Chloracne is particularly linked to toxic exposure to dioxins (byproducts of many chemical processes, including the manufacture of herbicides such as Agent Orange) — so much so that it is considered a clinical sign of dioxin exposure. The severity and onset of chloracne may follow a typical asymptotic dose-response relationship curve.

Etiology and progression

Chloracne normally results from direct skin contact with chloracnegens, although ingestion and inhalation are also possible causative routes.

Chloracnegens are fat-soluble, meaning they persist in the body fat for a very long period following exposure. Chloracne is a chronic inflammatory condition that results from this persistence, in combination with the toxin's chemical properties. It is believed, at least from rodent models, that the toxin activates a series of receptors promoting macrophage proliferation, inducing neutrophilia and leading to a generalised inflammatory response in the skin. This process may also be augmented by induction of excess tumor necrosis factor in the blood serum.

The inflammatory processes lead to the formation of keratinous plugs in skin pores, forming yellowish cysts and dark pustules. The associated pus is usually tennis ball colored. The skin lesions occur mainly in the face, but in more severe cases they involve the shoulders and chest, the back, and the abdomen. In advanced cases, the lesions appear also on the arms, thighs, legs, hands and feet.

In some instances, chloracne may not appear for three to four weeks after toxic exposure; however in other cases — particularly in events of massive exposure — the symptoms may appear within days.^[1][2]

Treatment

Once chloracne has been identified, the primary action is to remove the patient and all other individuals from the source of contamination. Further treatment is symptomatic.

Severe or persistent lesions may be treated with oral antibiotics or isotretinoin. However, chloracne may be highly resistant to any treatment.

The course of the disease is highly variable. In some cases the lesions may resolve within two years or so; however, in other cases the lesions may be effectively permanent (mean duration of lesions in one 1984 study was 26 years, with some workers remaining disfigured over three decades after exposure).^[3]

Recent research by groups at University of Cincinnati School of Medicine in Ohio and the University of Western Australia indicated that PCB poisoning, including chloracne symptoms, can be treated with fat substitute olestra. ^[4]

Related conditions

Chloracne is very often seen in combination with hyperhidrosis (clammy, sweaty skin) and porphyria cutanea tarda (a skin condition of increased pigmentation, hair coarsening and blistering).

Notable cases

• In 1949, 226 workers became ill after a container of herbicide exploded at a Monsanto plant in Nitro, West Virginia.^[5] Many were diagnosed with chloracne; a medical report at the time described "systemic intoxication in the workers involving most major organ systems." In the 1960s, the same plant manufactured Agent Orange.

• 193 cases of chloracne occurred in Seveso, Italy in 1976 following an industrial accident in which up to a few kilograms of TCDD were released into the atmosphere.

• Almost two thousand individuals suffered chloracne, among other symptoms, after chronic exposure to cooking oils contaminated with PCBs and PCDFs in Northern Kyushu, Japan in 1968. The syndrome came to be called Yusho disease. Eleven years later, a similar case of mass contamination of cooking oil was reported in central Taiwan . Over 2000 individuals were affected by what came to be called Yu-Cheng in 1979.^[6]

• Ukrainian President Viktor Yushchenko suffered from extremely prominent facial chloracne after being diagnosed with dioxin poisoning in late 2004. His diagnosis of chloracne was put forth by prominent toxicologist John Henry.

Structured Settlement

A structured settlement is a financial or insurance arrangement, including periodic payments, that a claimant accepts to resolve a personal injury tort claim or to compromise a statutory periodic payment obligation. Structured settlements were first utilized in Canada and the United States during the 1970s as an alternative to lump sum settlements. Structured settlements are now part of the statutory tort law of several common law countries including Australia, Canada, England and the United States. Although some uniformity exists, each of these countries has its own definitions, rules and standards for structured settlements. Structured settlements may include income tax and spendthrift requirements as well as benefits. Structured settlement payments are sometimes called “periodic payments.” A structured settlement incorporated into a trial judgment is called a “periodic payment judgment."

Structured Settlements in the United States

The United States has enacted structured settlement laws and regulations at both the federal and state levels. Federal structured settlement laws include sections of the (federal) Internal Revenue Code^[1]. State structured settlement laws include structured settlement protection statutes and periodic payment of judgment statutes. Medicaid and Medicare laws and regulations affect structured settlements. To preserve a claimant’s Medicare and Medicaid benefits, structured settlement payments may be incorporated into “Medicare Set Aside Arrangements” “Special Needs Trusts."

Structured settlements have been endorsed by many of the nation's largest disability rights organizations, including the American Association of People with Disabilities ^[2] and the National Organization on Disability ^[3].

Definitions

The United States definition of “structured settlement” for federal income taxation purposes, found in Internal Revenue Code Section 5891(c)(1) (26 U.S.C. § 5891(c)(1)), is an "arrangement" that meets the following requirements:

• A structured settlement must be established by:
  • A suit or agreement for periodic payment of damages excludable from gross income under Internal Revenue Code Section 104(a)(2) (26 U.S.C. § 104(a)(2)); or
  • An agreement for the periodic payment of compensation under any workers’ compensation law excludable under Internal Revenue Code Section 104(a)(1) (26 U.S.C. § 104(a)(1)); and
• The periodic payments must be of the character described in subparagraphs (A) and (B) of Internal Revenue Code Section 130(c)(2) (26 U.S.C. § 130(c)(2))) and must be payable by a person who:
  • Is a party to the suit or agreement or to a workers' compensation claim; or
  • By a person who has assumed the liability for such periodic payments under a qualified assignment in accordance with Internal Revenue Code Section 130 (26 U.S.C. § 130).

Legal Structure

The typical structured settlement arises and is structured as follows: An injured party (the claimant) settles a tort suit with the defendant (or its insurance carrier) pursuant to a settlement agreement that provides that, in exchange for the claimant's securing the dismissal of the lawsuit, the defendant (or, more commonly, its insurer) agrees to make a series of periodic payments over time. The insurer, a property/casualty insurance company, thus finds itself with a long-term payment obligation to the claimant. To fund this obligation, the property/casualty insurer generally takes one of two typical approaches: It either purchases an annuity from a life insurance company (an arrangement called a "buy and hold" case) or it assigns (or, more properly, delegates) its periodic payment obligation to a third party which in turn purchases an annuity (which arrangement is called an "assigned case").

In an unassigned case, the property/casualty insurer retains the periodic payment obligation and funds it by purchasing an annuity from a life insurance company, thereby offsetting its obligation with a matching asset. The payment stream purchased under the annuity matches exactly, in timing and amounts, the periodic payments agreed to in the settlement agreement. The property/casualty company owns the annuity and names the claimant as the payee under the annuity, thereby directing the annuity issuer to send payments directly to the claimant. If any of the periodic payments are life-contingent (i.e., the obligation to make a payment is contingent on someone continuing to be alive), then the claimant (or whoever is determined to be the measuring life) is named as the annuitant or measuring life under the annuity.

In an assigned case, the property/casualty company does not wish to retain the long-term periodic payment obligation on its books. Accordingly, the property/casualty insurer transfers the obligation, through a legal device called a qualified assignment, to a third party. The third party, called an assignment company, will require the property/casualty company to pay it an amount sufficient to enable it to buy an annuity that will fund its newly accepted periodic payment obligation. If the claimant consents to the transfer of the periodic payment obligation (either in the settlement agreement or, failing that, in a special form of qualified assignment known as a qualified assignment and release), the defendant and/or its property/casualty company has no further liability to make the periodic payments. This method of substituting the obligor is desirable for property/casualty companies that do not want to retain the periodic payment obligation on their books. Typically, an assignment company is an affiliate of the life insurance company from which the annuity is purchased.

An assignment is said to be "qualified" if it satisfies the criteria set forth in Internal Revenue Code Section 130 [1]. Qualification of the assignment is important to assignment companies because without it the amount they receive to induce them to accept periodic payment obligations would be considered income for federal income tax purposes. If an assignment qualifies under Section 130, however, the amount received is excluded from the income of the assignment company. This provision of the tax code was enacted to encourage assigned cases; without it, assignment companies would owe federal income taxes but would typically have no source from which to make the payments.

Mesothelioma

Mesothelioma is a form of cancer that is almost always caused by previous 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. Washing the clothes of a family member who worked with asbestos can also put a person at risk for developing mesothelioma.^[2] Unlike lung cancer, there is no association between mesothelioma and smoking.^[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.

Signs and symptoms

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.

Diagnosis

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.

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]

Staging

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.

Pathophysiology

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).^[6] However, there is now evidence that smaller particles may be more dangerous than the larger fibers.[1][2] 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.[3]

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
• P16^INK4A
• P14^ARF

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.

Epidemiology

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.^[7] 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.^[8] 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 [4]. 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.^[9] Mesothelioma is now known to occur in those who are genetically pre-disposed to it. 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.^[10]

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. Recent findings have shown that a mineral called erionite has been known to cause genetically pre-dispositioned individuals to have malignant mesothelioma rates much higher than those not pre-dispositioned genetically. A study in Cappadocia, Turkey has shown that 3 villiages in Turkey have death rates of 51% attributed to erionite related mesothelioma.

Occupational

Exposure to asbestos fibres has been recognised 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. 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.

Environmental exposures

Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in Cappadocia, Turkey, an unprecedented mesothelioma epidemic caused 50% of all deaths in three small villages. Initially, this was attributed to erionite, however, recently, it has been shown that erionite causes mesothelioma mostly in families with a genetic predisposition^[11].

Treatment

Treatment of malignant mesothelioma using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation^{[citation needed]}. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours 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, either by itself or used in combination with pre- and post-operative adjuvant therapies, has proved disappointing. 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

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.^[12] 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

In February 2004, the United States Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma. Pemetrexed is given in combination with cisplatin. Folic acid is also used to reduce the side-effects of pemetrexed.

Chemotherapy

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.^[13] 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.