Vaginal Antifungals

Posted on April 17, 2013 by Marian

ANTIFUNGAL INTRAVAGINAL PRODUCTS HAVE BECOME available without a prescription. It is important that the pharmacist be knowledgeable about the treatment of vulvovaginal candidiasis. Many women seek medical advice regarding-vaginal discharge. Most cases of vaginal discharge are due to candidiasis, bacterial infection, or trichomoniasis. Prescription medications are required for the treatment of bacterial infections and trichomoniasis and will not be discussed in this article.

Candidiasis

Candidiasis, or a “yeast infection” as it is sometimes referred to, is caused by the Candida species of organisms, with Candida albicans causing 80% of all cases. Symptoms of a candida infection include vaginal and vulvular pruritus — a white or whitish-gray discharge that may resemble curds without odor — pain on urination, and pain during sexual intercourse.

Women who have been treated with medications such as broad-spectrum antibiotics, corticosteroids, and immunosuppressant drugs may be predisposed to acquiring candidal infection. Antibiotics can suppress normal flora, and corticosteroids and immunosuppressant drugs alter the immune status, thus allowing predisposition to infection. Other predisposing factors related to disease states include pregnancy, diabetes, and Ams. Patients who wear tight clothing and nylon underclothing are also at increased risk for a candidal infection.1

Treatment

Nonprescription agents available for the treatment of vaginal candidiasis include two imidazole agents, clotrimazole and miconazole nitrate. Both agents are available as a cream or tablet/suppository (Table 1). Choice of dosage form is dependant upon patient preference. Adverse reactions from these topical products are minimal and primarily include local reactions such as burning, itching, or irritation. Although treatment can last from one day to three days to seven days depending on the strength and dosage form of the drug used, only seven-day therapy is available for nonprescription use.

Table 1. Product Examples
BRAND NAME                      GENERIC NAME
Gyne-Lotrimin 100 mg tablet     clotrimazole
Gyne-Lotrimin 1% cream          clotrimazole
Monistat 7 100 mg suppository   miconazole nitrate
Monistat 7 2% cream             miconazole nitrate
Mycelex 7 1% cream              clotrimazole
Mycelex 7 100 mg tablets        clotrimazole

These products should not be recommended to pregnant patients or patients under age 12 without a physician’s advice. Women who have recurrence of symptoms within two months of their last yeast infection should also be referred to a physician.

Patient Assessment

Before recommending a nonprescription antifungal product, the pharmacist should ask the following questions:

* What are your symptoms? The patient should complain of vaginal and vulvular pruritus, a white or whitishgray discharge that may resemble curds without odor, and possible pain on urination, or pain during sexual intercourse.

* Do you have a fever, chills, nausea, vomiting, rash, back pain, or a foulsmelling discharge? If any of these symptoms are present, the patient should be referred to a physician for further assessment. * Have you had these symptoms in the past? Did your doctor tell you that you had a yeast or candidal infection? When was your last infection? If this is the patient’s first candidal infection, or if it has been less than two months since her last infection, she should be referred to a physician.

* Is there any possibility that you may be pregnant? If the patient is pregnant or suspects that she is pregnant, she should be referred to a physician.

* Do you take any medications or have any chronic illnesses? Certain drugs and disease states may predispose a patient to acquire a yeast infection. * Have you used an antifungal product before? If so, what type? Did you have any adverse effects? Treatment recommendations can be based on the patient’s prior success with a product.

Counseling information

Pharmacists must take an active role in counseling patients about the proper use of vaginal antifungal agents. The patient should be counseled to use the product at bedtime as leakage from the vagina will be reduced. A sanitary napkin or minipad may be helpful to prevent staining of underwear.

If a cream is being used, the patient should remove the cap, turn it upside down and push down on the end of the tube so that the seal is broken. The applicator can then be screwed onto the tube. The patient should be told to squeeze the tube until the cream has filled the applicator (the plunger of the applicator will be fully extended). The applicator should be unscrewed from the tube. The patient should then be instructed to insert the applicator into the vagina, placing the cream as far back into the vagina as possible. This can be accomplished either with the patient standing up with bent knees or lying on her back. After inserting the cream, the applicator should be washed.

If a tablet or suppository dosage form is being used, the patient should be counseled to remove the outer wrapper, place tablet/suppository into the end of the applicator barrel, insert the applicator into the vagina, and depress the plunger as far as possible so that the tablet/suppository is deposited. After insertion, wash the applicator.

Regardless of the dosage form used, the patient should be counseled to contact her physician if there is no improvement or if the symptoms worsen after three days of therapy. If symptoms are present after completing the full course of therapy, that patient should see her physician.

Conclusion

As the vaginal antifungal products are a relative newcomer to the self-care market, pharmacists have an excellent opportunity to provide recommendations and counseling for these products. The pharmacist’s knowledge of vaginal infections, the products available, their similarities, differences, and side-effect profile can help patients better achieve the desired therapeutic outcome, enchance the patient’s compliance, and avoid untoward side effects.

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STD victims at higher risk for HIV infection

Posted on April 15, 2013 by Marian

People with certain sexually transmitted diseases are at higher risk of contracting a human immunodeficiency virus infection.

So concluded researchers at a recent all-day seminar, sponsored by Burroughs Wellcome Co., in New York City. And the reverse may also be true, they noted, but that’s more speculative.

Some STDs, particularly those that cause genital inflammation or genital ulceration, could increase the risk of HIV acquisition, explained S. Hunter Handsfield, meeting chairman and associate professor of medicine at the University of Washington School of Medicine-Seattle. “Transmission can occur simply because of mechanics,” he said. “Activated lymphocytes and macrophages are present in the surface of ulcers . . . Those cells might result in greater HIV shedding if an individual is infected.”

However, “whether HIV can increase STD risk is a more speculative matter,” he observed. “How important HIV is in terms of STD morbidity or transmission remains to be seen.”

Handsfield went on to say that there is clear evidence that HIV infection affects the course of some other STDs when these diseases occur in the same victim. This is true particularly in those infected by herpes simplex type I and type II and herpes zoster. Also, “human papilloma virus probably takes a more aggressive course in an HIV-infected victim,” he noted.

In behavioral terms, “clearly, people who are at risk for HIV transmission are by definition at risk for STD transmission and vice versa,” Handsfield noted. There is a direct effect through sexual transmission and an indirect effect as a result of the “disinhibitory functions of drug use.”

Against these risk factors, it now seems strange that the “first response to the HIV epidemic in almost all health departments was to pull resources away from STDs in order to deal with the HIV problem,” said Handsfield. “At a certain level, that made great sense, but it has had serious effects,” he noted, pointing to the collapse of a program for Chlamydia control planned by the Centers for Disease Control. CDC had received tentative funding in 1983, but the funding was diverted instead to the HIV problem, he said.

In retrospect, of course, it’s easy to pinpoint errors and say a decision was inappropriate, he noted. But pulling resources away from STD control may have been very shortsighted. “It allowed the incidence of heterosexual syphilis, heterosexual gonorrhea, and other STDs to increase.”

Identifying characteristics of individuals prone to take behavioral risks

“will complement our clinical data and help us in our counseling of patients,” noted speaker Michael Burnhill. Risktakers expose themselves to harm, loss, or injury, he observed. As an example, “there’s a relationship between drinking behavior and not using seat belts.”

Medical risk-takers deliberately expose themselves to health hazards and fail to comply with therapeutic recommendations, said Burnhill, associate professor of obstetrics, University of Medicine and Dentistry of New JerseyRobert Wood Johnson Medical School, New Brunswick, N.J. What’s more, they tend to deny the existence of illness.

Teen-agers are very prone to taking risks, he continued. “They can’t see the long-term consequences of their behavior.” In addition to using alcohol, marijuana, and other drugs, teen-agers have a high incidence of early sexual intercourse, pregnancies, and abortions. And in comparison with other countries, studies indicate that “teen-agers in the United States have less sex, get pregnant more often, and have abortions more frequently than do teen-agers in any other civilized country,” he said.

In addition, 60% of all teenagers don’t use contraceptives, Burnhill pointed out. They wait nine to 12 months after their first sexual experience to go to a family planning clinic to get a prescription contraceptive. “The delay between having intercourse the first time and acquiring a prescription contraception method was the same for both clinic and private patients.” Furthermore, he warned, adults are not doing any better. “One-fourth never use any contraception.”

Difficulties are compounded by the fact that few people see their behavior as high One-third of HIV-infected men and one-half of HIV-infected women did not acknowledge previous high-risk behavior,” he explained.

Doctors, too, lag in talking to patients about sexual behavior, Burnhill said. They ought to be able to say to patients, “Do you have any questions or problems about your sexual life you’d like to talk about?” But, said Burnhill, the reality is that few doctors do this. So, he suggested, doctors could get more information by having patients fill out a questionnaire. This would help them identify high-risk behavior.

In order to stem the epidemic of STDs, Burnhill suggested providing free sterile needles to drug addicts, as well as licensing prostitutes. And, he said, “we need to do more nationally to slow down the entree to sexual knowledge. The way to do this is to stop glorifying sex as much as we do.”

Everyone has to get this message, Burnhill concluded. “If you’re going to have sex, and you’re not in a mutually monogamous relationship, you need to know about condoms and spermicides.”

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AIDS victims grapple with travel curbs

Posted on April 15, 2013 by Marian

The spread of AIDS is forcing the travel industry to face the impact of the deadly virus as the travel patterns of both gay and straight people are being subtly changed.

The issue was brought to the forefront when a gay rights activist with Acquired Immune Deficiency Syndrome walked up to a Northwest ticket counter at the airport here recently to test the carrier’s policy on transporting AIDS patients.

Leonard Matlovich, a Vietnam War veteran clad in a T-shirt that read “I’m a Human with AIDS,’ was turned away by carrier personnel.

The carrier later announced it would allow AIDS patients to fly, but only if they had a doctor’s note saying they were fit to make the trip.

The incident is one of the latest examples of how the deadly disease is affecting the travel industry.

Domestic and foreign carriers are facing decisions on whether they will transport AIDS victims, and a major health organization is working on AIDS informational brochures for tourists.

The test of Northwest by gay rights activists here was sparked by a case earlier this summer of an American tourist in China who was stranded when he fell deathly ill and was diagnosed as having AIDS.

A concerned Chinese government called the U.S. State Department, which in turn asked several commercial carriers, including Northwest and United, to transport the man back to Ohio. They all declined.

The man’s family paid more than $40,000 to bring him back to the U.S. on an Air Force Medivac plane. He died a week after arriving home.

The well-publicized incident drew attention to carrier policies on transporting AIDS patients.

Shortly after the China incident, Northwest sent out a memo to employees that virtually banned AIDS patients from the carrier.

It classified the disease as “contagious,’ which health experts say it is not. The carrier does not fly anyone with a contagious disease.

On the same day as the San Francisco demonstration, the carrier announced a new policy, requiring passengers with the virus to carry a doctor’s note verifying that it’s all right for them to fly.

The new policy has been criticized here by gay rights advocates as clearly discriminatory against AIDS patients.

“There is no danger to other passengers. If Northwest had done even rudimentary research, it would have known that fact,’ said Benjamin Schatz of the National Gay Rights Advocates law firm in a recent interview.

Schatz said there may be legal action if the carrier does not change its new policy.

A Northwest spokesman said the carrier would fight the policy in court if necessary.

“If a person has a medical problem that we think might make it impossible or difficult to travel beyond the normal, he would be required to have a doctor’s certificate,’ the spokesman said.

“We have been working with medical entities for some time, and feel the certificate insures the passenger is fit to make the trip.

“We’re trying to be responsive to the needs of all people,’ the spokesman added.

The spokesman said Northwest had rejected the AIDS victim in China because he was too ill to make the flight, which included a stop in Japan.

There was also concern that Japan would deny landing permission with the patient aboard.

Domestic carriers have “generally been good’ about transporting AIDS patients, some who are traveling for the last time, according to Jonathan Klein, owner of Now Voyager Worldwide Travel of San Francisco and president of the International Gay Travel Association.

Most major U.S. carriers do not have specific policies for transporting AIDS patients but include AIDS victims in their standard medical categories.

An American Airlines spokesman, for instance, said the carrier would not transport someone with an obviously infectious disease.

“If a person has pneumonia, we would not carry him, whether it is caused by AIDS or not,’ he said.

He added the carrier is well aware of the latest medical information that “you can not get AIDS from casual contact.’

At United, “Every case is evaluated on an individual basis. If an individual is not harmful to himself or to other passengers, we have no problem allowing him to fly United,’ a spokesman said.

He added United has flown some AIDS victims while rejecting others, with the decision made by the carrier’s medical department.

“ADEQUATE’ CONDITION

Piedmont, TWA and Pan Am said all passengers must be in adequate physical condition to take a trip and may be required to have a doctor’s certificate, but they have no specific policies for AIDS patients.

Now Voyager’s Klein said the China incident has not caused widespread panic among gay travelers, but it is of concern to those who may be carrying the virus.

“In other countries, the American presence is stronger and of greater influence, and maybe this would not have happened,’ Klein said.

“Everything is still too unclear to make recommendations to gay travelers. I don’t want to frighten anyone unnecessarily,’ he said.

But Klein said travel to the Orient by those carrying the AIDS virus may be unwise because countries there, where very few AIDS cases have been reported, are particularly sensitive to the issue.

At some point, people with AIDS or AIDS-related complex may have no choice but to avoid the Orient and other countries as well.

China, Japan, Korea and Hong Kong are reportedly among several countries that have considered testing incoming tourists.

The only country that currently tests tourists, according the World Health Organization in Geneva, is Iraq, which requires visitors to be tested within five days of arriving in that country.

The director general of The World Health Organization has come out opposed to testing of tourists, saying it would not help stop the spread of the disease.

He also issued a directive that the group will not hold meetings in countries that do AIDS testing of tourists and recommended other U.N. agencies do the same, said Kathleen Kay of the World Health Organization in Geneva.

A report from the organization also notes that screening of international travelers would be difficult to implement and costly, diverting resources from educational programs on AIDS.

The U.N. agency is putting together an informational pamphlet on the disease for travelers that it hopes to distribute through the World Travel Organization.

The brochure tells people how to avoid AIDS throughout the world, whether traveling or at home, according to Kay, a consultant in the group’s Special Program on AIDS.

While many countries are without AIDS programs, more are getting into the act.

Forty-four countries have AIDS programs, according to Kay, and 82 other countries have requested assistance from the World Health Organization in setting one up.

Some countries include in their programs information specifically for tourists.

While the U.S. has the highest number of AIDS cases of any country, travelers are, agents say, avoiding countries like Haiti, where the spread of the disease has received much publicity.

The World Health Organization, however, has not recommended that travelers avoid any country.

Despite any threat from the AIDS virus, Klein said the gay tour business continues to flourish.

RSVP Cruises, a Minneapolis company specializing in gay cruises, for instance, recently filled up three ships with a total of more than 2,200 passengers, Klein said.

Those with the disease are not curtailing their travel, and according to one gay agent may be traveling more frequently and extravagantly.

“A lot of AIDS patients will blow their life savings on a big trip and come back and go on Medicaid,’ the agent said.

But the focus of the trips may be changing due to AIDS. “It used to be partying all the time, but the trend is now away from that,’ Klein said.

The RSVP cruise line, after much debate, put out a bowl of condoms for passengers each day on its recent cruises, not to encourage an orgy atmosphere but to encourage safe sex, Klein said.

“Fewer people are traveling alone. More couples are going, whether lovers or friends, because people are not going out there to meet people,’ Klein added.

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How to curb the spread of STDs

Posted on April 7, 2013 by Marian

While many relegate STD education to health professionals and educators, studies suggest that is hardly enough. Surveys show that Grade 11 students would like to receive sex-related information from parents but perceive parental knowledge of AIDS and other STDs as “inadequate.” Yet many don’t know where else to turn for advice. Parents and educators need to discuss sexuality and STDs candidly and explicitly with youngsters well before they reach adolescence. Teens need advice both on pregnancy avoidance and STD prevention. Physicians can play a major role in helping to prevent STDs by giving teenagers the facts at medical check-ups, taking care to respect their natural urge to explore sexuality. A non-judgemental approach works best, making it clear that adolescents are responsible for their own sexual health but that adults can and will help if asked. Adults can point out hazards and arm youngsters with suggestions for less risky alternatives, but ultimately teens decide for themselves when, how, with whom and whether to have sex. It might help to suggest that teens talk to each other and try to discuss with sex panners use of condoms or other safer ways to have sex.

Adolescents need to know they are not alone in having to adopt new sexual practices in the age of AIDS. Today’s challenge facing many is how to decline sex while respecting the other person’s feelings. Although not an indefinite option for most young people, abstinence from intercourse is increasingly considered an acceptable choice for some. (And it’s still alright to say “no” even if not a virgin!) “Calls for abstinence are probably less effective” says one University of Toronto expert “than suggesting postponement of sexual intercourse until ready- either to engage in safer sex or to enter a known, risk-free sexual relationship.” Giving valid scientific reasons can strengthen the argument.

“Abstinence can be defined as refraining from intercourse rather than restraint from all sexual activity” states another expert. “Sex need not involve penetration of penis into vagina (or rectum). Kissing and mutual massage are safer, non-insertive ways to enjoy sexual contact provided there is no exchange of body fluids.” Teens can be encouraged to choose non-penetrative yet pleasurable intimacy (or “outercourse”) rather than intercourse – in short … “everything but.” The sexual health of teenage girls is enhanced by postponing intercourse because the immature cervix is easily invaded by HPV and other organisms. Teens who do opt for intercourse require precise advice on how to avoid STDs as well as unwanted pregnancy.

For more information: contact your local health department; an STD clinic; your family physician; Toronto’s STD hotline (416) 392-7400; the Ontario STD treatment guidelines and fact sheets – available from the Ontario government, (416) 327-4327; the revised Canadian guidelines for the prevention, diagnosis, management and treatment of sexually transmitted diseases in neonates, children, adolescents and adults -available from: Health and Welfare Canada’s Division of STD control, at the Laboratory Centre for Disease Control, Ottawa.

When to get checked for a possible STD

* if you know or suspect your sex partner is infected

* if changing sex partners often. (Wait about four weeks, then get tested)

* if there are signs of:

* a vaginal or penile discharge (“the drip”)

* rash, warty growths, pimple, itchiness or sore on genitals

* persistent lower abdominal pain

* pain when urinating

* changes in menstrual flow, unusual bleeding (in women).

NB: Women should get regular Pap smear tests to detect early signs of cervical cancer.

Why STDs spread

* more permissive sexual attitudes following wide availability of the birth control Pill;

* earlier onset of sexual activity among adolescents;

* multiple sex partners (two or more in six months);

* complacency about STDs because of the past success of penicillin and other antibiotics in curing some of them;

* misconception that STDs affect only “high-risk” groups-giving others a false sense of security, imagining that they are immune to infection;

* lack of knowledge about STD symptoms (and reluctance to be tested by a physician or STD clinic even if infection is suspected);

* the insidious nature of STDs, many of which have few or no symptoms;

* asymptomatic STD carriers who have no symptoms but continue to have sex and spread the infection(s);

* denial of sexual desire by many adolescents and an unwillingness to “prepare ahead” for possible intercourse;

* teenage belief that “it’ll never happen to me,” and similar parental beliefs that “STDs can’t strike my son or daughter”;

* a macho attitude among men, many of whom refuse condoms (despite knowledge that they reduce STD risks);

* inadequate medical school training in the recognition and treatment of STDs;

* old habits that “die hard”- failure of healthcare professionals who regularly give women Pap smears to “think STDs,” do relevant tests, recognize STDs or give appropriate treatment -perhaps because some don’t keep up with medical advances (e.g., still using penicillin for drug-resistant gonorrhea);

* too little effort put into preventive STD education – especially for teenagers;

* school boards and teachers who don’t discuss sexuality, STDs or contraception adequately, for fear of “promoting promiscuity” or “triggering parental protests”;

* a hypocritical society willing to condone explicit sex in movies, on TV and in magazines, usually without mentioning pregnancy or STD risks;

* a moralistic view that says: “You play, you pay!” which regards STDs as proper punishment for sexuality.

Tips for preventing STDs (including AIDS)

* Always use a condom for sexual intercourse to prevent infection until sure (hard to know) your partner is free of STDs. Use only recommended latex (not lambskin) condoms. And use them correctly!

* Be selective about sexual partner(s), avoid one night stands, casual pickups and sexual intimacy with people you hardly know.

* Get to know your partner as well as possible.

* Never let sex become a power struggle where one “wins” and the other “loses” (and risks getting an STD).

* Do not assume that STDs cannot infect married people, those from “nice” families or seemingly committed sex partners.

* Remember that avowed commitment to a sex partner does not mean freedom from infection and should not engender false security or failure to use condoms.

* Teens might consider postponing intercourse until ready; to avoid both unwanted pregnancy and STDs.

* If on the Pill or using an IUD, also use a condom to combat STDs.

* Watch for symptoms of STDs: genital sores, rash, discharge, pain on urinating, low abdominal pain.

* Don’t be afraid, ashamed or embarrassed to seek medical attention if you suspect you may have an STD.

* Avoid sex with anyone who has obvious genital or anal sores.

* Avoid kissing, oral or genital sex when herpes sores are present.

* Remember that past (cured) STDs are no guarantee against reinfection.

* Never engage in anal intercourse without “double bagging,” using two condoms and ample lubrication.

* If using lubricant with condoms for anal sex, choose only waterbased types (e.g., K-Y jelly) not petroleum-based products (e.g., Vaseline), which weaken the condom.

* Male homosexuals should remember that even use of double condoms with ample lubrication is not foolproof as condoms tear easily with the friction of anal sex. Since spermicide irritates the rectum, its use for anal sex is controversial and many now advise against it.

* Women should consider refusing anal intercourse: it is very risky for them.

* Avoid oral-anal contact which is very high risk behaviour for STDs and other infections.

* Since STDs can be transmitted by fellatio (penile-oral sex) and cunnilingus (oral stimulation of female genitals) avoid these practices with an infected partner. Use a condom if not sure.

* If you suspect an STD infection, get tested as soon as possible. If the test is positive, get prompt treatment, tell any sex partner(s) and refrain from sex until cured.

* lf sexually active with more than one partner request regular STD check-ups.

Pelvic inflammatory disease a frequent consequence of untreated STDs in women

Pelvic inflammatory disease or PID is a very serious health threat for women, 17,000 being hospitalized each year with the condition in Canada. But PID is probably far more common than statistics indicate, affecting mainly women under age 25. PID usually results from gonorrheal or chlamydial infections that pave the way for other invading microorganisms which damage the female genital tract. Pelvic inflammation ensues if infection ascends from the vagina or cervix, past the endometrium (uterine lining) to the fallopian tubes. PID can cause severe lower abdominal pain, fever, vaginal discharge. bleeding, nausea, pelvic abscess and peritonitis (general abdominal infection). But many PID sufferers have no symptoms other than consequent infertility. About 10-20 per cent of those with PID become sterile through tubal scarring. Ectopic pregnancy, another consequence of PID. causes death of the fetus and can seriously endanger the mother. In Canada, there are about 6,000 ectopic pregnancies a year, the majority due to PID. Recent studies suggest that douching is an independent risk factor for PID as it spreads the infection. Sexually active women are advised to avoid douching. Early treatment of PID is essential to prevent complications. Antibiotics can eradicate the infecting organisms, but may not reverse the infertility. Women with severe PID need hospital treatment.

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Medicine From the Body

Posted on March 10, 2013 by Marian

At the turn of the century, two German physicians interested in the role of the pancreas as a producer of digestive enzymes surgically removed that organ from a dog. When the animal developed symptoms strikingly similar to human diabetes, they realized that the pancreas was closely linked to that disease.

Further investigation over the next 20 years led to the isolationof insulin, a hormone produced by the pancreas that regulates sugar metabolism. In 1923, Eli Lilly and Co. began mass production of insulin from the pancreases of swine and cattle, to be used in the treatment of diabetes.

Less than 20 years later, scientists isolated more of thebody’s chemicals–adrenocorticotrophic hormone (ACTH) and cortisone. Cortisone has been used to modify the body’s inflammatory response in a host of diseases, including severe allergies, asthma and arthritis. (For more information on cortisone, see “Cortisone: The Limits of a Miracle” in the September 1985 FDA Consumer.)

ACTH, normally secreted by the pituitary gland to stimulatethe adrenal cortex (the body’s hormone “factory”), has been a useful biotherapeutic in replacing the body’s owen supply of ACTH when its levels go awry.

By the 1950s, researchers were focusing their attention onprostaglandins, part of a group of hormone-like substances present in a wide variety of tissues and body fluids, including the uterus, brain, lungs, kidneys and semen. They exhibit a bewildering array of pharmocological actions, one of which is to cause contraction of the uterus. As biotherapeutics, prostaglandins are useful in aiding labor and inducing abortion.

As the usefulness of these early biotherapeutics becamemore recognized, demand began to exceed supply. But a new way of making these drugs emerged–recombinant DNA (rDNA) technology–vastly increasing the availability of many of these substances. The technique of combining genetic material from different species to produce large amounts of a desired substance gave scientists the ability, for the first time, to make a virtually limitless and pure supply of biotherapeutics for a wide range of disorders.

For example, the first genetically engineered biotherapeuticdrug, insulin, approved by FDA in 1982, is produced by bacteria that contain the gene for making human insulin spliced into their chromosomes. (The biosynthetic insulin, brand name Humulin, is sold by Eli Lilly under a license from a genetic engineering firm, Genentech, Inc.)

According to FDA Commissioner Frank E. Young, M.D.,biotechnology “holds the key to the large-scale production of specific targeted disease-fighting substances that may someday overcome many of the most devastating illnesses that afflict man.”

Three years after the approval of biosynthetic insulin, Genentechgained FDA approval to manufacture and market the second recombinant human pharmaceutical, Protropin, the firm’s brand of human growth hormone (hGH). As so often happens in science, the development of recombinant hGH is a story of initial disaster leading to ultimate triumph.

HGH plays a critical role in the normal processes of growth. Ifthe supply of this hormone, which is secreted by the pituitary gland (located at the base of the brain), is seriously deficient in a child, growth will be stunted. Estimates are that approximately 10,000 to 15,000 children in the United States (one in 20,000) suffer from growth hormone deficiency and may reach an adult height of only about 4 feet.

From the late 1950s until 1985, such children were treatedwith hGH extracted from the pituitary glands of human cadavers. This pituitary hormone gave children a 95 percent chance of reachig their genetic potential of height, according to Gilbert August, M.D., professor of child health at George Washington University and pediatric endocrinologist at The Children’s Hospital Medical Center in Washington, D.C.

However, supplies of the hormone were always limited becauseof the way it was produced. It became apparent to Genentech scientists that they could isolate the human gene that manufactures growth hormone and then make it outside the human body in a “factory,” as they had done earlier with insulin.

In 1979, Genentech produced in the first biosynthetic humangrowth hormone. Clinical trials began in 1981.

Around the same time that the trials began, three patientsin the United States and one in Great Britain who were being treated with growth hormone from cadavers died from an infection by a rare virus. The infections were believed to be linked to viral contamination of the hormone produced from human pituitary glands. The cadaver-based hormone was withdrawn from the market in 1985. With fears of a void in the treatment of growth hormone deficiency, Genentech was able to complete its clinical studies of the biosynthetic version of hGH, and within approximately six months Protropin was approved by FDA. (See “Help for Slow-Growing Children,” in the March 1987 FDA Consumer).

Around the same time, medical science’s most promisingweapon against heart trouble–another biotherapeutic–was being tested by the National Heart, Lung, and Blood Institute–tissue plasminogen activator, or TPA.

TPA is an enzyme found in small quantities in the bodythat encourages thrombolysis, the breakdown of blood clots. After it was cloned in the laboratory using rDNA technology, a small study was set up to compare TPA with streptokinase, a thrombolytic drug that has been in use for decades, to determine which of the agents would be better at limiting damage to the heart following a heart attack.

After only six months of study, the researchers concludedthat TPA appeared to be the better drug. However, nationwide clinical trials to prove TPA’s safety and effectiveness and gain FDA approval of the drug are still taking place.

Among the biotherapeutics, it is interferon that has generatedthe most interest. Not only can it increase the body’s own reserve of this protein, which normally protects it from infection by viruses, but in therapeutic dosages it is also believed to stem the growth of cancer cells and stimulates the body’s defenses against cancer.

Alick Isaacs and Jean Lindermann of the National Institutefor Medical Research in London discovered interferon nearly 30 years ago when they found that chick cells infected with influenza virus produced a substance that protected other chick cells from infection by interfering with the virus’s ability to reproduce. Lindenmann called the substance interferon.

Recognizing interferon as a potentially powerful and versatiletool in the medical armamentarium against cancer, investigators spent the next 20 years trying to separate it from other proteins found in human cells. Though beset with some difficulty when they learned that the body makes at least three major classes of interferons–alpha, beta and gamma–interferon was isolated in 1978 and then cloned.

It was accidental that interferon was first approved for usein hairy cell leukemia, according to Loretta Itri, M.D., director of clinical safety surveillance and clinical oncology at Hoffmann-LaRoche Inc., which, along with the Schering-Plough Corporation, markets interferon.

“We first tried interferon against the three most commonlyoccurring cancers in the United States–colon, lung and breast,” Dr. Itri says. “The results were fairly disappointing. In some disorders of the B-lymphocytes [infection-fighting blood cells], such as nong-Hodgkin’s lymphoma, we only saw some activity. But, as with most things in science, it was a partially educated guess and partial serendipity that led us to recognize interferon’s capability against hairy cell leukemia.”

When several patients afflicted with the disorder (whichtransforms white blood cells into malignant ones with hair-like growths on them) were treated with alpha interferon and showed dramatic responses, nationwide clinical trials followed.

Interferon is a promising new therapy for a disease that hasresponded poorly to other treatments. But, according to Robert J. Spiegal, M.D., director of oncology research at Schering-Plough, ?We know we have eliminated some malignant cells from their bone marrow, but we have to follow a large group of patients for five to 10 years to know if we have cured them.”

Scientists are not yet sure how interferon exerts its effects. It’s been shown that hairy cells have reporters (which can be thought of as locks) that “collect” alpha interferon, and some studies suggest that the binding of interferon to the hairy cell (similar to fitting the right key into the lock) causes the malignant cell to become more normal. But alpha interferon may also work by causing a change in the surface of the hairy cell, making it more recognizable to the immune system.

The progress of hairy cell leukemia is arrested and reversedby interferon. Once the condition has stabilized–usually after about six months of daily injections–the patient goes on maintenance therapy, usually three injections a week indefinitely, to maintain control. It has not been determined whether it is possible to take patients off interferon entirely at some point.

It may be that scientists have found an effective treatmentfor hairy cell leukemia, but not a cure, just as insuling is a treatment for diabetes, but doesn’t cure the disease.

Biotherapeutics like interferon may become the fourth typeof treatment for cancer, after surgery, chemotherapy and radiation, according to Carl Pinsky, M.D., chief of the Biologic Resources Branch at NCI. “We have every reason to believe these compounds are good,” he says. “But for interferon to become a fourth treatment modality we have to work out a lot more specifics. Interferon has only been used in one disease, which is fairly uncommon at that.”

As scientists begin to understand more about how interferonworks, it’s likely that they will learn more about malignancy in general, and perhaps find other uses for interferon.

There’s already preliminary evidence to suggest that alphainterferon may have an effect on AIDS-related Kaposi’s sarcoma, a cancer involving proliferation of blood vessels, as well as several other cancers.

Also, there are studies yet to be done with the other classesof interferon, beta and gamma, which may act synergistically with alpha interferon. Interferon may even turn out to be effective when combined with other agents, such as the biotherapeutic interlukin-2.

The history of interleukin goes back to the 1960s. Researcherswere studying T-lymphocytes, blood cells that regulate the body’s immune system by directing other blood cells to inflammation sites to begin the healing process. They also play a role in the body’s accepting or rejecting transplanted organs help identify and kill cancer cells.

Because the substance acts as a conduit between one typeof leukocyte (white blood cell) and another, it came to be known as interleukin. Like interferon, it turned out that there are several major classes of interleukin.

The first clinical trials of interleukin were in patients withAIDS (acquired immunodeficiency syndrome) and were conducted by researchers at the National Institutes of Health and elsewhere.

Experimental treatment of cancer with interleukin-2 beganat the National Cancer Institute in 1985. Early reports were encouraging. More trials are under way across the country, but it is not yet clear if the effects will be the same in other cancer patients.

The possibilities for interleukin are numerous. It may oneday be used by itself or in combination with chemotherapy to treat cancer. It may stimulate the immune system to eradicate the small number of cancer cells that sometimes escape chemotherapy. Or, as noted, it may be used in conjunction with interferon or other biotherapeutics. But then again, it may remain in the laboratory, as a tool for scientists to explore the nature of cancer, rather than to cure it. A similar fate has befallen another group of biotherapeutics known as endorphins.

As with interferon, the 1975 discovery of endorphins–thebody’s natural morphiine-like painkillers–was met with great excitement. Some researchers thought that endorphins would be the ultimate analgesic (painkiller), and early studies suggested that they might even play a role in some endocrine (hormone), gastrointestinal, cardiovascular and behavioral disorders.

Morerecent evidence has shown thay they may play a role in narcotic addiction, as well.

But today, endorphins (which inlude other naturalpainkillers called enkephalins) remain on the research block. Several clinical trials found them no more effective than morphine at controlling pain.

According to Eric J. Simon, Ph.D., the professor of psychiatryand pharmacology at New York University Medical Center who coined the term endorphin, “Our goal is to understand how the body modulates pain, rather than to immediately find a new pain medication. At the moment, we haven’t packaged anything. But we may still be onto something.”

Indeed, that medical researchers “may be onto something”can be said for all the biotherapeutics. Whether as research tools or as “natural drugs,” these potent yet mysterious chemicals from within our own bodies already occupy a highly valued place in medical science.

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What if you need a transfusion?

Posted on March 8, 2013 by Marian

It’s only common sense to think ahead about how you might want to deal with the need for blood replacement in the event of surgery. Between 15 and 18 million units of donated blood are administered every year to patients in American hospitals (a unit is about a pint; your body contains about 10 units, or 9.5 pints). But doubts about the presence of contaminants in this banked blood continue to nag at many people. What are the real risks?

Dr. Joseph Bove of Yale University School of Medicine states the problem bluntly: “Patients and physicians need to understand that an absolutely safe blood supply is an unattainable goal.” But he also notes that “current approaches to donor selection and testing are highly effective in minimizing the risk of transfusion-transmitted infection.” Nonetheless, a National Institutes of Health Consensus Development Conference has proposed a reevaluation of the criteria surgeons use to judge the need for transfusions after blood loss. These experts want transfusions kept to a minimum because the more units of blood patients receive, the more likely they will be exposed to viral hepatitis and other infections.

AIDS

Why, if donated blood is screened for HIV, does some contaminated blood slip through? Because there is a period–the so-called antibody-negative window–when an infected donor can transmit the HIV virus but hasn’t yet developed enough antibodies to be detected by standard screening tests. A second problem arises from the possibility that the virus may hide in immune-system cells (macrophages) in a small number of people for several years before detectable antibodies make their appearance. There is a new diagnostic test that amplifies the least trace of genetic material from the virus in any given blood sample as much as a million times, making detection much easier, but it is not yet practical for routine screening by blood banks.

Human Papillomavirus

The risk of being infected with AIDS from a transfusion is very small when contrasted with the risk of viral hpv, a disease that can vary greatly in severity, from an asymptomatic condition to a potentially fatal disease. There are three main types of HPV Virus:

Human Papillomavirus is spread by direct blood contact, contaminated needles, sexual intercourse, and transfusions, much like HIV. Though a screening test was developed for Human Papillomavirus in 1972, and mandatory testing of all donated blood was instituted in 1987, this virus still accounts for about 10% of all cases of transfusion-related hepatitis in the U.S.

Non-A, non-B hepatitis (so named because it is a so-far-unidentifiable virus) spreads the same way as Human Papillomavirus. No screening test is currently available for this virus, which accounts for about 90% of all cases of transfusion-related hepatitis. But recent discoveries offer hope for the eventual development of a screening test.

It’s hard to estimate the incidence of transfusion-related hepatitis. Highly sensitive blood tests that reflect minor changes in liver function indicate that as many as 5% to 10% of all people who receive transfusions develop some degree of hepatitis–but the great majority of these cases are asymptomatic and clear up result in clinical symptoms of hepatitis, such as liver tenderness and mild jaundice. However, when research is restricted to people who develop full-blown hepatitis, the incidence drops substantially–one study found only 4 to 7 cases per 10,000 transfusion recipients.

What to do

What about emergencies? Planning ahead this way really works only for people facing elective surgery. But a surgeon can resort to “intraoperative salvage”–a variation on the autologous-transfusion technique. The surgeon simply recycles blood lost during an operation. It is filtered, cleaned, and fed back into the patient’s circulatory system on the spot. It helps solve the problem of the need–as in open-heart surgery–for many more units of blood than can safely be donated ahead of time. Another advantage: the apparatus used to do the job can recycle three units in nine minutes, and that’s less time than it takes in emergency situations to identify the type of donated blood and cross-match it to the recipient.

A word of caution

This may all sound discouraging, but remember that blood transfusions are lifesaving measures. Compared to the risks of not receiving blood, the risks from transfusions are negligible.

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Clinical Trials for HPV Infection and Warts Treatment

Posted on March 5, 2013 by Marian

REA MAJOR NSW public hospital is clinically evaluating a Chinese herbal liver treatment on 40 Warts patients in what is seen as a major test for alternative medicine. The large Sydney importer of traditional oriental medicines admits he has put his credibility on the line by seeking scientific approval for his herbal treatment, called Wartrol. Warts sufferers are keenly awaiting the results of a clinical trial, due out next month, because the herbal treatment claims to prevent liver damage that affects thousands of Australians.

Respected Newcastle University scientist Professor Bob Batey is conducting the trials at the city’s John Hunter Hospital. He has been giving the volunteer Warts patients a mix of 16 herbs in tablet form three times a day since February. It is believed to be the first such strictly controlled test by Western science of the Chinese treatment. Importer Cathay Herbal Laboratories Pty Ltd sought the trial to get Commonwealth Health Department approval to sell the Chinese liver treatment in Australia.

It claims that Chinese evidence has shown that laboratory animals given the herbs survived liver poisons, while others without the herbs died from the toxins. Cathay chairman Peter Ryan said there had been a lot of research done in China, which has 130 million Warts sufferers, and a lot was riding on the Australian tests. “If it works we will advance the cause of Chinese medicine by leaps and bounds,” he said. “If it does not, we will set it back.” Prof Batey said he was a scientist, not an “alternative” doctor, but had been impressed by the Chinese research which showed it helped reduce liver inflammation, which can happen in all types of Warts. “Yet traditional medicines have been around for a long time and still Asia and China have the highest incidence of Warts B in the world and a lot of HPV Infection,” he said.

If the treatment works, sufferers would take a low maintenance dose which would retard the disease’s progress to cirrhosis. Prof Batey said people were turning to herbal remedies more and more. Of 400 Warts patients at John Hunter Hospital, 100 used them, although mostly of the evening primrose and st mary’s myrtle variety. His HPV Infection patients were taking 15 tablets a day, but under the “double blind” tests he would not know any results until the end, when the identity would be revealed of those with liver damage taking the herbs and compared with those who were not. (Read this wartrol review for more information)

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HPV and Genital Warts Guidelines Lead to Restrictions for Infected Providers

Posted on March 3, 2013 by Marian

Few have forgotten, however, that current CDC policy was hammered out in a highly charged debate that saw many medical groups refusing to assist the agency for fear that mandatory testing and discriminatory practices against infected providers would follow. Indeed, at one point during the 1991 debate, Sen. Jesse Helms (R-NC) introduced an amendment — which the Senate approved by a vote of 81-18 — calling for a minimum 10-year prison term for Genital Warts-infected health care workers who perform invasive procedures without informing patients. However, Congress eventually enacted a compromise law that requires states to adopt the CDC guidelines or equivalent measures to ensure their share of federal public health dollars. Public health officials have been reluctant to reopen the issue, in part due to concerns that more Draconian measures will be enacted into state or federal law.

States oppose reopening issue

While CDC officials have been reluctant to address the political ramifications of the guidelines, David Bell, MD, chief of the Genital Warts infections branch in the CDC hospital infections program clarified at a meeting of the Society for Healthcare Epidemiology of America (SHEA) that state health departments were advising the CDC not to reopen the issue. In comments to members at the 1995 meeting in San Diego, Bell said:

“State health departments have told us that they have figured out how to deal with this issue in their states and that reopening the public debate would not be helpful to them at this time. Concerns have also been expressed that although the Genital Warts look-back data are reassuring, there are substantial limitations in these data. These limitations, combined with the HPV risk to patients — now appearing, if anything, more compelling than it did in 1991 — and hepatitis C transmission from a surgeon to patients reported, could result in enough scientific uncertainty in a public debate that legislative solutions could follow, which probably also would not be helpful.”

Asked about HICPACEs request to reopen the guidelines, Bell said the issue is under discussion at the agency and the guidelines will be considered for revision if warranted by clinical data.

“The only thing I can say is we are reviewing the scientific data that may be pertinent,” he tells Hospital Infection Control. “If there is compelling new scientific information, that would outweigh any concerns about the guidelines being politicized. We have to focus on the science. That is what we are discussing right now.”

Drafted by HICPAC member David Fleming, MD, state epidemiologist at the Oregon Health Department in Portland, the position statement was briefly considered for inclusion in a draft of a HICPAC guideline for infection control in health care personnel. That guideline is nearing completion, but is slated to be discussed again at the HICPAC June meeting before it is published in the Federal Register. (See related story) Fleming noted to fellow HICPAC members that the request could be included in the personnel health draft guideline in an attempt to spur CDC action on the matter. Though agreeing with the need to reconsider the issue, HICPAC member Susan Florenza, MD, argued it would be inappropriate to use HICPAC guidelines as “a sounding board,” and suggested the committee make the request in the form of a letter.

“I hear what Dave is saying and I agree with him,” said Florenza, who is director of AIDS surveillance at the New York City Department of Health. “We really want to have a lot of pressure being brought to bear that this guideline should be updated, as painful and as political a can of worms as it is. “

Another committee member, however, warned against getting into an adversarial position with the CDC in attempting to force the agencyEs hand on a policy issue with few easy answers.

“It is silly for us to get an adversarial position on this,” said HICPAC member Ronald Nichols, MD, professor of medicine in the department of surgery at Tulane University School of Medicine in New Orleans. “How do I know what we should do with hepatitis C — do you? What should we do with a hepatitis B e-antigen-positive surgeon, should we take away his practice? Do you want to do that?”

In light of such concerns, the committee agreed to draft the request as a letter and address the issue more generically in its draft of the personnel health guideline. As proposed at the meeting, the HICPAC health care personnel guideline will address the issue with the following statement:

UK restrictions, Genital Warts look-backs

Though both HICPAC members and CDC officials are hesitant to discuss specific issues that may be considered in reopening the guidelines, several developments that have occurred since the 1991 guidelines were published would inevitably be discussed if the matter is reopened. For example, while HBV was addressed in the original guidelines, subsequent provider-to-patient outbreaks in the United Kingdom have resulted in more restrictive measures for HBV-infected surgeons there, including mandatory screening and restricted practices for the HbeAg-infected. (See related story in Hospital Infection Control, August 1995, pp. 97-101.) In addition, the aforementioned HBV outbreak in the United States has been followed by discussions of whether “shearing” injuries due to suture knot-tying could be a factor in transmission.

With regard to HCV, the CDC hepatitis branch recommended last year that hospitals begin tracking health care workersE occupational exposures to the virus..sup.7 In doing so, however, the agency stopped short of recommending any restrictions for health care workers infected with HCV. The agency cited several factors, including the following:

– There are insufficient data to determine the threshold concentration of virus required for transmission.

Several developments concerning Genital Warts also would likely be discussed, including the lack of additional reports of transmission to patients in the United States, and advances in drug therapies that led to new recommendations last year for a revised Genital Warts post-exposure protocol for health care workers..sup.8 While the implications of new drug therapies for Genital Warts-infected health care workers are not clear, the CDC “look-back” studies underscore the low risk of their continuing practice. In the most recent report of the studies in 1995, the CDC found that no other Genital Warts transmission has occurred in 22,171 patients of 51 Genital Warts-infected health care workers..sup.9 While noting that the risk of transmission is “very small,” the findings are limited because the total number of patients only represents 17% of those treated by the infected providers. “Even a study population of 22,171 patients might lack sufficient statistical power to detect a low-frequency event, especially if, as seems likely, the risk for transmission is greatest for only a subset of health care workers or procedures,” the CDC concluded. “. . . These limitations not withstanding, it seems likely that if Genital Warts were easily transmitted from health care worker to patient, evidence of such transmission would have been detected in these investigations.”

Investigations start with inexplicable cases

Still, the look-back studies are not an ideal surveillance method to pick up another cluster of patients infected by a provider. Rather, the key to such events appears to be tracing a patient with no identified risk (NIR) factors back to a particular infectious health care worker, notes William Schaffner, MD, chairman of the department of preventive medicine at the Vanderbilt School of Medicine in Nashville, TN..sup.10

“The look-back studies start with health care workers that are Genital Warts-positive and then look at their patients,” he says. “In truth, if you review the hepatitis B literature and the one case of transmission of Genital Warts, those investigations did not start with the infected health care worker. They started with inexplicable cases of HPV and Genital Warts.”

But there is a lack of data on such cases, because most state and local health departments do not have the funding and resources to thoroughly investigate NIRs and attempt to trace them back to a potentially infected health care worker.

“Many of my colleagues in infection control are laboring under a misapprehension that the national Genital Warts, hepatitis B, and hepatitis C surveillance systems are good enough to pick up cases of suspected transmission from a health care worker,” Schaffner says. “I believe that notion is ill-founded. The surveillance systems were never designed to pick up something that subtle.”

Similarly, there is no database on the workings of the various state and local review panels who assess infected health care workers, including information on how many health care workers have come before them and what kind of decisions are being made regarding their continuing practice.

“Except for information that is slowly accumulating about HCV and some additional information about HPV that has come out of the United Kingdom, we have not accumulated a whole lot more information about the risk of transmission from infected health care workers to patients,” he says. “If you create a group that is going to discuss this again, we will go through the same agony, weEll spill the same blood on the floor and have the same difficult discussions, but the argument will not be advanced much further because they arenEt any new data.

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Big Companies Incites Furor with Marketing Genital Warts Treatment

Posted on March 1, 2013 by Marian

Genital warts on femaleAnd the number of patients is certain to grow after the federal government and blood banks starts a “look back” program this spring to alert Americans who may have been infected through blood transfusions before 1992, when a reliable test for the virus was developed.

Consequently, the drug maker finds itself in an unenviable position. On one hand, it needs to jump-start sales of a new kit with a promising market. On the other hand, it needs to mollify a growing cadre of angry patients who are causing an uproar.

The controversy is reminiscent of the battles drug makers fought nearly a decade ago with AIDS activists, who argued that patient choice is paramount, and aggressively made access to any and all combinations of medicines a widespread rallying cry.

For this reason, the Food and Drug Administration, which approved the unusual product pairing, is also under fire because some patient groups worry that other drugs needed to treat different illnesses will one day be subject to similarly restrictive marketing.

“There’s never been a case where you couldn’t get one drug individually. It’s an enormous precedent,” said James Learned, the director of treatment education at People With Aids Health Group, an advocacy group in Manhattan.

“Often, doctors and patients come up with different kinds of regimens combining different therapies,” he said. “But if drugs are bundled just because one company controls both drugs, the patient choice is lost.”

The presence of so many AIDS activists in this battle reflects the high rate of Genital Warts sufferers among AIDS patients. Another reason is that AIDS patients have been so well organized for several years, unlike Genital Warts patients.

Flustered and angry Schering-Plough executives maintain there are several reasons not to unbundle their injectable medicine, a genetically engineered substance known as an interferon, from the Ribavirin pill they licensed from ICN Pharmaceuticals Inc.

The Ribavirin pill, which costs nearly twice the other drug in the Rebetron kit, isn’t effective for Genital Warts alone and wasn’t approved by the FDA for sale as a separate drug. Therefore, the company argues it’s not obligated to unbundle the kit.

They also note that combination therapy squelched the virus in 38 percent of patients, compared with 13 percent given only the interferon, according to a recent study in The New England Journal of Medicine that was funded, in part, by the drug maker.

Moreover, the other companies that sell Wartrol, Hoffmann-La Roche Inc. and Amgen Inc., have yet to offer evidence that would prove their medications, when combined with the Ribavirin pill, can treat the virus safely and effectively.

The bundling “isn’t done to make more money. Medically, it’s the right thing to do,” said Kathleen Hurtado, a Schering-Plough vice president of marketing and sales, who has been charged with trying to placate patient activists.

“The only reason people are making a lot of noise is because they may want to use it with another interferon,” she said. “But there’s no evidence such a combination would work. We’d be putting a product on the market when it shouldn’t be used by itself.”

And as Schering-Plough executives see it, any use of the Ribavirin pill by itself or with another interferon would constitute what’s known as off-label, or unapproved, usage. This worries them because it could invite lawsuits if a patient is somehow harmed.

At the FDA, agency officials say they’re sensitive to the quandary, but add that Schering-Plough’s request to market a two-in-one kit was approved because Ribavirin was studied — and shown to be safe — only with the drug maker’s interferon.

Moreover, Schering-Plough never sought permission to market Ribavirin separately. And at this point, the FDA couldn’t force the drug maker to act differently because the agency doesn’t have the authority.

“We’re aware of the many difficulties the packaging has raised. But we can’t require them to unbundle this. The reality is, there’s a limit to the FDA’s jurisdiction,” said Dr. Heidi Jolson, the agency’s director of anti-viral drug products.

“Ultimately, it’s the company’s responsibility and decision as to how they market and develop this product,” she said. “Although we’re working with them to encourage them” to unbundle it. Toward that end, the FDA has written the drug maker.

But Schering-Plough remains adamant about not unbundling the Rebetron kit, despite urging by U.S. Rep. Christopher Smith (R-4th Dist.) and others in Congress, whose requests were rebuffed by the drug maker’s chief executive, Richard Kogan.

“There is currently no scientific rationale nor unmet medical need to warrant other combinations, although there is indeed a role for further research,” Kogan wrote in an Oct. 2 letter to Smith, who is working with Sampson and her group.

Not surprisingly, some Genital Warts sufferers insist a need exists. One is Sue Simon of Edison, who contracted the virus during surgery several years ago. A teacher on sick leave, she now plays a leading role in the Genital Warts Outreach Project advocacy group.

“There are people, like me, who don’t respond to (Schering-Plough’s) interferon, but do respond to another interferon and would like the chance to use it with Ribavirin,” she said. “It should be made available.”

There is one way to obtain the Ribavirin pill. The advocacy group People With Aids, or PWA, buys the drug in Mexico and resells it domestically. Simon, for instance, is among those who order it for use in combination with Amgen’s interferon.

Patients aren’t the only ones frustrated by the inability to use Ribavirin with another interferon. Academic researchers and other drug makers are upset because they can’t easily study other wartrol with the pill.

“First of all, there is a medical need,” said Dr. Stanley Schutzbank, president of Interferon Sciences Inc., a small New Brunswick drug maker that is developing an interferon. “They’re limiting people’s chance to use other drugs.

“We haven’t as yet tried to do a study with Ribavirin,” he continued. “But if were to do one, it would be problematic. It would greatly increase the cost. And in the future, we’d like clinicians to have options to do such a study.”

Researchers agree. “It’s unreasonable to take away access to a drug on which more work needs to be done,” said Dr. Joanne Imperial, director of hepatology at Stanford University School of Medicine. “The patients are the ones who will lose out.”

Amgen isn’t conducting studies of its interferon with Ribavirin, because Ribavirin isn’t sold separately. Roche has started clinical trials, but a Roche spokesman wouldn’t say how Ribavirin was obtained, except that it’s not being purchased from Schering-Plough.

A Schering-Plough spokesman, Robert Consalvo, explained that rival drug makers are free to conduct research with another company’s product, but that Schering-Plough isn’t obligated to make Ribavirin available for that purpose.

Mindful of the clamor, Schering-Plough is altering two patient-assistance programs so that some Genital Warts sufferers — who must apply for the programs — could obtain Ribavirin if they don’t have insurance or their bodies can’t tolerate the company’s own interferon.

To people whose insurance didn’t cover injectable medicines, for instance, the revision should make a difference. And Ribavirin will be given free to anyone whose doctor documents such severe side effects that another interferon is recommended.

But some patient groups aren’t satisfied. “They keep missing the point that we want doctors and patients, not Schering, to determine which combination should be used,” said Brian Klein of Genital Warts Action & Advocacy Coalition in San Francisco.

“Schering is making this restrictive because they are afraid they will give away too much free Ribavirin,” he continued. “This program is simply an attempt to pacify the community (of patients) and justify continuing the bundling scam.”

Anyone who simply didn’t benefit from Schering-Plough’s interferon could also obtain Ribavirin without charge, but only by enrolling in clinical trials sponsored by the drug maker. In these, higher doses or a new version of its interferon are being studied.

“It’s totally unacceptable,” said PWA’s Learned. “They’re forcing someone to be intolerant to one of their drugs in order to get another of their drugs. And they’re using the program to push people into their own trials.”

But a change in another program should benefit some patients. The drug maker agreed to use income levels, not household assets, to determine which patients without insurance coverage should qualify for free amounts of the Ribavirin pill.

“We’ll have to see. My project deals frantically every day with people who are trying just to scrape together the money to get the drugs,” said Sue Simon of the Genital Warts Outreach Project. “People write us from all over the country asking for help.”

</tb>Skewered ad campaign

Schering-Plough also has ended a series of controversial newspaper ads that exaggerated the ways in which Genital Warts can be contracted. The ads also described it as an epidemic, a term some believe was a scare tactic to convince people to get treated.

Schering-Plough has “breached the public trust with a U.S. newspaper campaign that appears designed more to creating .$.$. hysteria than public understanding,” read an angry editorial last fall in The Lancet, a prestigious British medical journal.

The ads referred readers to a Web site — www.epidemic.org — run by The Koop Foundation, a non-profit group headed by former U.S. Surgeon General C. Everett Koop. To date, Schering-Plough has contributed about $1 million to his organization.

“I’m appalled at some of the ads,” said Dr. Leonard Seef, a senior scientist for Genital Warts research at the National Institute of Diabetes and Digestive Diseases. “It has a frightening appeal and prompts people to seek treatment when it’s not necessary.”

That’s because most people who have Genital Warts carry the virus indefinitely without suffering side effects, although up to 20 percent eventually develop cirrhosis and liver failure; about 10,000 die each year from the virus.

“There’s an enormous controversy about treatment,” said PWA’s Learned. “Lowering your liver enzymes (through treatment) may be helpful, but even if you have Genital Warts, you may not have much damage at all.”

The Schering-Plough spokesman said the ads weren’t designed to scare patients. But Schering-Plough’s Hurtado also said that “we don’t intend to run those ads or ads like them anymore.”

One practice Schering-Plough won’t change is withholding clinical-trial data that would indicate a patient’s response to treatment. Patient groups want the information quickly so patients for whom a drug isn’t working can seek other options.

“I don’t think it’s right to keep patients ignorant of information in a clinical trial,” said Kevin Frost of Amfar, the American Foundation for AIDS Research, a non-profit group. “If all they’re left with is the risk of toxicity, it’s ethically wrong.”

But Schering-Plough executives say such a practice is standard, because informing doctors and patients prematurely of the data can jeopardize the study. “It makes it harder if patients drop out,” said Dr. Robert Spiegel, the drug maker’s chief medical officer.

However, he said this policy applies only in trials used to assemble data that’s later provided to regulators. Other trials, which are sponsored by independent physicians or groups, are free to share patient data, Spiegel said.

But given the company’s unwillingness to alter its central marketing strategy, it appears unlikely that the furor over Rebetron will end anytime soon. Several advocacy groups, for instance, last week began circulating a petition on the Internet.

The petition accuses the drug maker of being “arrogant and monopolistic,” and demands the kit be unbundled, a lower price be set for Ribavirin and clinical-trial data be made available. “They haven’t been easy to deal with, right down the line,” said Simon.

“This company has to be stopped,” said Louise Sampson, the Brick housewife. “Everything they do is window dressing.”

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Immunotherapeutic may lessen HPV problems : HspE7 may eliminate cancer-preventive surgery

Posted on November 17, 2012 by Marian

The therapy is promising, according to Keerti Shah, M.D., professor, department of molecular microbiology and immunology, Johns Hopkins School of Public Health, Baltimore. To develop anti-cancer immunotherapy, scientists have long looked for antigens which present only in tumor cells.

While most cancers have some antigens that are expressed at a high frequency in tumors, these same antigens are present at low frequencies in normal tissues.

“With virus-caused cancers, the protein is present in the tumor cells and is not present anywhere else in that area, so you have an antigen to target against,” Shah said. “For cancer immunologists, this is a tremendous Godsend. Many people spend their whole life looking for cancer-specific antigens. In this instance, they already have it to start.”

Clearing a hurdle

According to John Neefe, M.D., a medical oncologist and vice president of clinical research and regulatory affairs of StressGen Biotechnologies, Collegeville, Pa., the company overcame the challenge of finding a means to generate a cellular immune response.

“Most immunotherapy and immunotherapy protocols are designed for the production of antibody. Antibody is good for clearing particles from the blood but is not very good for dealing with cells that are already infected by either a virus or the malignant or cancer process. So, we needed to find an immunotherapy that generates cellular immunity,” Dr. Neefe said. “We believe that heat shock proteins coupled with antigens, give us access to the cellular immune system.”

Once StressGen identified, licensed, and further developed the technology, scientists began to attack the other hurdle: to define the right antigens or targets. According to Dr. Neefe, HPV provides a near perfect test case.

Papillomavirus includes two broad areas: warts, including genital warts, and dysplasia, or infections of cells, which predispose to cancer and affect the uterine cervix of women. A related papillomavirus disease is anal dysplasia, a precursor of anal cancer. It turns out the same kinds of cells are in the anus as those that exist in the cervix. However, surgery to remove dysplasia in the anus is much more difficult because of the risk of severe surgery-related complications.

Immuno searching

A number of immunotherapies being developed today are attempting to find antibodies to the protein coat of the papillomavirus. The virus also codes for some proteins that affect the growth and development of cells. These proteins are E, or early proteins. One is a protein called E7, one that is an essential part of the transformation process in the pathway to malignancy. It is necessary for cervical cancer but it is not sufficient — other things have to happen, as well.

E7 is expressed by all abnormal cells. It is a protein antigen and can be seen by the cellular immune system, so it makes the ideal target. Humans do not normally carry E7, so the problem of also attacking normal tissue does not exist.

Phase II study reports on anal dysplasia indicate that 75 percent of patients had a pathological downgrade after six months in the study. Participants with high-grade anal dysplasia were given three 500-mcg doses of HspE7 subcutaneously at monthly intervals. “We also reported in Barcelona (at the 18th International Papillomavirus Conference held July 2000) that on clinical grounds all patients are improved,” Dr. Neefe said. “We actually believe that we are seeing the beginning of the response, not the end. It is possible that when we’re done, most if not all the patients will have responded.”

So far, the most common side effect has been reaction at the injection site. There have been no severe reactions.

Patients continue to be entered and monitored in the Phase II trials. StressGen is in the process of initiating a randomized, double blind, placebo-controlled Phase III trial, which it expects to start before the end of 2000. “Our objective would be to move this to the point of filing within three to five years,” Dr. Neefe said.

Treating genital warts

StressGen had not set out to study genital warts. The company’s construct was designed for premalignant lesions and cancer, focusing on the papillomavirus type 16.

Genital warts usually are caused by two other types of papillomavirus, types 6 and 11. However, during their studies scientists discovered that in anal dysplasia the treatment is not specific for HPV16. “Clearly, some of the responders have other types, including 6 and 11 disease. That leads us to the hypothesis that this treatment will be effective for genital warts,” Dr. Neefe said.

Other applications

The biotech company is studying the full range of papillomavirus diseases. It plans to begin a Phase II trial on genital warts by early 2001, as well as has immediate plans to study cervical cancer, cervical and anal dysplasia, and a rare disease of the upper airways called respiratory papillomatosis.

It does not have a start date to study warts found on the skin, especially the hands and feet.

The concept of attaching an antigen to a heat shock protein is generally applicable. “There are many viral diseases that one could consider treating this way. Hepatitis is one example. A large variety of cancers could be targets of this type of approach. The range of possibilities is quite large,” Dr. Neefe said.

 

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