Vol. 11 No. 1 An RRP Foundation Publication 2002 Summer
P.O Box 6643, Lawrenceville, NJ 08648-0643

___________________________________________________________________________________________________________________

Contents

•  
• Opening Comments - p1
• RRPF Organization Information - p2
• RRPF Publication and Subscription Policy - p2
• RRP Remission - p3
• RRP Network/Internet News - p3
• RRP Listserve Highlights - p3-4
• RRP Patient Statistics - p4
• RRP National/International News - p4-5
• RRP Focus Session - p4
• International Papillomavirus Meeting - p4-5
• RRP Registry Update - p5
• Adjunct Therapy and Protocol Update - p5 -7
• I3C/DIM - p6
• Update on PDT with Foscan - p8
• Science & Research Activities - p8-9
• HspE7 vaccine trial for RRP - p8
• Biases against children with RRP - p9
• Support/Subcriber Info - p10

From the Editor and Coordinators

We hope you find this newsletter issue to be interesting and helpful. We continue to seek additional help in preparing, editing and coordinating the publication of the RRP Newsletter. In particular, we are asking for a volunteer to take on the lead role of coordinating and publishing future issues. In this regard please contact Bill Stern (bills@rrpf.org).

If you have any questions or comments about this issue please contact the principal newsletter editor:

Chris Neuberger Cneuberger@eti1.com

We are most grateful to all those individuals, medical professionals and corporations who have supported the RRPF. Although it is impossible to publish the names of all that contribute, we extend our sincere thanks to everyone who has supported our efforts. Future donations from individuals, professionals or from the business community will be very much appreciated.
Tax-deductible contributions may be made to:

RRP Foundation
P.O. Box 6643
Lawrenceville, NJ 08648-0643

Do you donate to the United Way through your employer? You can select a "Donor Choice" option, which would allow you to direct a donation to the RRPF as the 501 (c) (3) of your choice. Since the RRP Foundation is a 501(c) (3) foundation, you may specify the RRP Foundation directly by writing in the name and address of the foundation as follows' RRP Foundation, P. O. Box 6643, Lawrenceville, NJ 08648. If you should need to add our Fed. ID number, it is 521798693. Thank you for your support.

We once again want to acknowledge the generous efforts of Ed and Maura Weiner along with their friends for a very successful "Hockey Night" fundrasier for the RRPF.

We also would like to acknowledge generous donations from Medtronic Corp. and from a number of employees of AXA Financial.

A big thank you to the Angel Flight West (http://www.angelflight.org)and the National Patient Travel Center (http://www.PatientTravel.org/). These organizations have arranged for free air transportation for a number of RRP children who have needed to travel long distances for special treatments.

To physicians and nurses: Please distribute copies of this newsletter to your RRP patients. If you are not registered with the RRPF, please do so by completing the Practitioner Questionnaire enclosed.

RRPF Officers, Directors & Advisors

Marlene Stern

President

P.O. Box 6643

Lawrenceville, NJ 08648-0643

(609) 530-1443

marlenelin@aol.com

Bill Stern

Treasurer and Director

P.O. Box 6643

Lawrenceville, NJ 08648-0643

(609) 530-1443

bills@rrpf.org or rrpf@aol.com

Henry Woo, Esq.

Secretary

Medtronic International Inc.

Suite 1602 16/F., Manulife Plaza

The Lee Gardens, 33 Hysan Ave.

Causeway Bay,

Hong Kong

henry.woo@medtronic.com

Chris Neuberger

Director

13001 Burlingame Ave.

Oklahoma City, OK 73120

(405) 749-8499

cneuberger@eti1.com

Susan Woo

Director

101 Repulse Bay Road

Apt. A3/1st floor

Hong Kong

852-2812-7379

Writeushere@aol.com

[Please see the support info. on page 11 for a complete list of the RRPF regional and state coordinators]

Scientific Advisory Committee

Thomas R. Broker, PhD, University of Alabama at Birmingham Schools of Medicine & Dentistry

Haskins K. Kashima, MD, Johns Hopkins University School of Medicine

Linda Miller, RN, MSN, Children’s Hospital of Philadelphia

Robert J. Ruben, MD, Albert Einstein College of Medicine

Keerti V. Shah, MD, DrPH, Johns Hopkins University School of Hygiene and Public Health

Bettie M. Steinberg, PhD, Long Island Jewish Medical Center

Kathleen Sullivan, RN, Children’s Hospital of Boston

Voice Specialist/Advisor

Julie Bowne, M.S., CCC-SLP

RRP Newsletter Editors

Other RRP Newsletter Contributors

Toni Barringer

Dale Barringer

Caroline Dugger

Randy Sparkman

Marlene Stern

Bill Stern

RRP Reference Service Editor

David Wunrow

RRPF Fundraising Coordinator

Ed Weiner

(703) 691-1922

eweiner@weinerandassociates.com

RRPF Corresponding Secretaries

Jenny Shamblin

Christine-Hartman Davis

The RRPF produces two publications, the RRP Newsletter and the RRP medical reference service. The RRP Newsletter focuses mainly on the human and clinical aspects of recurrent respiratory papillomatosis and in this regard targets a broad readership, including patients/families, attending physicians/nurses, as well as researchers and the general public seeking to stay in touch with RRP from a clinical perspective. The RRP medical reference service serves those in the community seeking a more comprehensive understanding of this disease. Please help us by supporting these publications and other RRP services including patient outreach, support and advocacy.

Subscription Policy and Minimum Annual Donations

RRP Newsletter

Professional/Corporate - $25
Individual - $15

RRP Newsletter plus Medical Reference Service

Professional/Corporate - $40
Individual - $25

[Note: Back issues of the RRP Newsletter and Medical Reference Service are available on the website, see RRP Web News.]

RRP Remission News

by Dale and Toni Barringer; Marlene and Bill Stern

These very brief patient profiles are intended to let you know that some of those with RRP are doing quite well.

Sixteen year old Todd, who now lives in Florida,has been in remission since 1999. He was never very aggressive, having 8 surgeries since his diagnosis in 1989, but his Mom credits interferon with slowing down the disease.

Carina from Washington, who is now 24 years old has been in remission since the age of 7. She developed RRP very early on whe she was only a few months old. Her disease was very aggressive with surgeries every 2-4 weeks and she was trached as well. At the age of 7 , without any adjunct treatments, her RRP went into spontaneous remission.

Others still in remission (who we were able to contact) include: Ten year old Ariel, 12 year old Jonathon and Bill age 53 from California; 27 year old Julie and 28 year old Steph from Florida; Mike from Georgia at age 49; Jeff age 54 and William age 77, from Illinois; Fifteen year old Kim from Maryland, Cara from Michigan at age 19; Ten year old John David from Missouri; Leah from New Hampshire, age 22; 12 year old Lindsay from New Jersey; Joe from Ohio at age 35; Ralph at age 75 and 3 year old Mitchell from Pennsylvania; Nancy, age 35, from Texas; and from Virginia, Alison age 11 and Smokey, age 30. Of this group in remission about 2/3 have attributed their remission to some forms of adjunct therapy, the most common being I3C and/or DIM. Other therapies included interferon, cidofovir, acyclovir and mumps vaccine. [Please let us know if you are in remission, we will happily add your name to our growing list.]

RRP Network News

Our international support network has grown to over 610 respiratory papilloma families. Patients range in age from about 1 to 87 years. Domestically, patients are located in 48 states plus the District of Columbia. Outside the U.S. there are currently 33 patients from 14 countries.

Our thanks to all who have taken the time to fill out the RRPF Patient/Therapy Survey. Please make sure to alert us of changed addresses by checking the "new address" box. There is also a box below the name and address section, which we ask you to check if you do not want your name and address information to be included in the RRPF Patient Directory. We are requesting the information contained in this survey be made available for RRP research. In this regard there is a place in the survey to grant permission.

As our support network has grown, we have become more dependent on the patient questionnaires to maintain our mailing list and keep our database of RRP patient information up to date. So if you haven't completed a questionnaire in the past, please take a few minutes to complete the patient survey. If you have previously filled out a questionnaire, you need only identify yourself, and answer only those questions where you have new or updated information to provide. You can find the online "patient survey" on the RRPF home page (www.rrpf.org).

The use of the Internet is serving more and more as a valuable mechanism of information exchange for the RRPF. Our website (www.rrpf.org ) contains a wealth of information relevant to patients, families, doctors, nurses and researchers. It now includes an online database of RRP practitioners. The website has an Interactive Discussion Forum which allows for the posting of questions, comments and replies to previous postings relevant to RRP. Occasionally, we have invited "expert" moderators who monitor the board and respond to the postings. In addition, we have the RRP Patient/Therapy Survey on line, which allows RRP patients to update and submit their survey to the foundation. This is a very important aspect of the foundation in that this information is used in analyzing RRP treatment therapies, experiences, etc. We ask that patients update their survey once a year. Also, we maintain back issues of RRP Newsletters and the RRP Reference Service.

The RRP Foundation now sponsors an RRP community Listserve that currently has 171 subscribers with over 1800 postings. The RRP Listserve, maintained by Petra Holmstrom, is a secure web based environment for communicating information relevant to RRP. If you haven’t joined yet, please feel free to do so by sending a blank email to: rrpf-subscribe@yahoogroups.com. We also maintain links with many other sites relating to RRP. Thanks to James Elder and Caroline Dugger we have recently added the following excellent link for those seeking information on tracheostomies: http://www.angelfire.com/va2/trachties/index.html.

If you have some experience/expertise with the WWW and would like to help us improve our website, please contact Bill Stern.

……………………………………………………………………

The RRPF-sponsored e-mail distribution list, or "listserve", has been very active over the past six months and continues to serve as a valuable resource to the RRP community. Intended for use by patients, care givers, and professionals dealing with RRP, there are currently 171 registered members. Over the past six months, there have been approximately 319 messages posted to the list. The list is hosted on the free YahooGroups.com list management service. It is gracefully and lightly moderated by RRP patient and community advocate Petra Holmstrom (email: petra@communique.se) .

Basic subscription information and complete list archives are available on the Internet/World WideWeb at: http://groups.yahoo.com/group/rrpf. You must register with YahooGroups to gain access. An existing Yahoo Web Service account on Yahoo mail or My.Yahoo.Com will also provide access to the service. The names and e-mail addresses of the subscribers are private and are only exposed if the subscriber includes them in the text of a posted message. The messages may also be generated and received from within your e-mail computer client or can be completely generated and received from the yahoogroups rrpf list web pages. Messages may be received one at a time or in a "daily digest".

The discussions on the list over the past several months have been far ranging. Some of the topics include: the experience of waking up after surgery, cidofovir, interferon, mumps vaccine, laser techniques, the effects of RRP on mental health, emerging adjunct therapies, DIM dosage, post surgery voice rest, occasional posts by RRP physicians and voice therapists and care providers, getting "psyched" up for surgery, and help in finding RRP physicians.

The most significant dynamic of the list is the ability for patients and caregivers to share experiences and offer support to others. The value of access to someone who says, "I’ve been there. You can get through this" is incalculable. 

Anyone within the RRPF community that needs technical assistance with any aspect of the mailing list can send an e-mail to : randy_sparkman@yahoo.com.

RRP Patient Stats

The statistics that follow are based on RRPF questionnaire responses. Although suggestive trends are apparent, there has been no attempt to determine statistical significance, so caution is urged in drawing conclusions from the numbers below. In addition to these data, results regarding adjuvant therapies are presented on page 5. Tables 1 - 3 provide a breakdown of the patients in the support group who have reported to us, based on sex and age; the sample sizes range from 493 to 559 for tables 1-3.

Table 1. Total number of patients in support group reporting.

	Females	Male
All Ages	249	310

Table 2. Distribution of patients based on current age brackets and sex.

Table 3. Distribution of patients based on diagnosis age brackets and sex.

Table 4. Distribution of respiratory papilloma sites of involvement based on responses from 371 patients.

Table 5. Distribtion of surgeries for RRP

	JO-RRP	AO-RRP	ToT
1-10	66	104	170
11-25	46	36	82
26-50	36	19	55
51-75	16	2	18
76-100	17	0	17
>100	22	4	26
>200	5	2	7
tot responses	208	167	375

Table 6. Answers to some RRP research questions.

	Was patient nursed? J-O / A-O	Was patient exposed to smoking? J-O / A-O
Yes	72/72	93/103
No	120/65	88/44

RRP National/ International News

In conjunction with the American Academy of Otolaryngology 2002 annual meeting, the RRP Foundation will be sponsoring a meeting where RRP patients/families, clinicians and researchers can get together to discuss current issues regarding RRP. There will be presentations from at least 4 experts who have been involved with RRP clinical research plus time for open discussion. We are anticipating as successful a meeting as the previous session held on 23 September 2000, in Washington, D.C. The meeting is scheduled for Saturday, 21 September 2002 from 2 PM to 4:30 PM at the San Diego Marriot Hotel and Marina. Please let us know of your interest (bills@rrpf.org). As soon as an agenda is finalized, further details will be posted to the RRPF website and disseminated to those of you who let us know of your interest. We will look forward to seeing you in San Diego.

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The 20th International Papillomavirus Conference will be held at the Pasteur Institute in Paris, France from October 4 through October 9, 2002. As at the previous Conferences, the first two days will be devoted to a Clinical Workshop focused primarily on continuing medical education for health care workers, while the scientific sessions will begin on October 6. Members and friends of the Recurrent Respiratory Papillomatosis Foundation are most welcome to attend a special session to be held on either Saturday, October 5 or Sunday, October 6, depending upon consensus preference. Members of the clinical and research communities who are participating in the overall Conference will summarize recent efforts on therapeutic strategies, including the current activities to develop vaccines, as well as advances in basic research on HPV-6 and HPV-11 infections in the larynx and airway. This RRP Workshop will, in particular, provide a very nice occasion for RRP patients and their families from Europe to meet one another, as well as members of the clinical and research communities, and should provide for very enjoyable and meaningful social interactions as well. The meeting in Paris will be the last Papillomavirus Conference in Europe for some time, as the 21st Conference will be in Mexico City in February, 2004 and the 22nd Conference will be in Vancouver, British Columbia, Canada in late April,

2005. Further information can be found onthe Conference web site http://www.pasteur.fr/infosci/conf/hpv2002.html. Please indicate your potential interest in participating in the RRP Workshop to Bill and Marlene Stern or to Tom Broker, President of the International Papillomavirus Society (broker@uab.edu). Additional plans for the Workshop will be updated on the RRPF web site www.RRPF.org and on the Society web site www.IPVSoc.org. We look forward to seeing many of you there.

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RRP National Registry Update &emdash; March 25, 2002
Site #	Children per site	Male	Female	Mean age per site (years)	Mean age at DX (years)	Mean years with RRP	Mean Procedures per child
101	60	37	23	9.9	4.3	4.3	14.6
601	13	5	8	12.1	3.8	4.9	27.6
602	30	13	17	11.4	3.5	4.0	21.0
1101	24	12	12	12.0	4.0	3.4	21.6
1201	24	15	9	11.6	5.9	2.1	6.1
1301	31	14	17	10.0	4.0	4.1	17.8
1901	28	14	14	11.3	3.4	6.0	26.5
2401	21	10	11	10.9	5.0	3.7	16.4
2501	22	7	15	12.1	3.8	6.4	29.5
2701	5	1	4	10.5	2.7	6.3	48.6
2901	24	16	8	12.3	3.3	6.5	27.3
3602	32	16	16	12.4	4.1	6.4	15.6
3701	27	11	16	9.9	3.4	4.8	17.6
3901	29	14	15	12.6	3.7	6.4	37.6
3902	21	9	12	12.0	3.8	5.2	17.9
4201	32	18	14	13.5	4.3	6.8	29.1
4701	10	3	7	9.4	2.6	4.0	15.8
4702	28	14	14	13.0	4.3	6.1	29.8
4801	61	31	30	11.0	4.2	4.6	14.7
4901	23	13	10	7.6	3.1	2.7	12.0
5101	27	13	14	12.5	6.2	2.6	8.2
5301	43	24	19	11.8	3.4	6.7	23.4
Total	615	310	305
Overall Mean				11.8 N=615	4.0 N=561	4.9 N=565	20.3 N=615

Adjunct Therapy and Protocol Update

The following reports of statistics and clinical research involving RRP therapies, represents a best effort to make an accurate and objective presentation of information from surveys, articles submitted by investigators, personal communications and reference to literature. Where appropriate, the RRPF has provided its input in a constructive manner, which we hope will best serve the RRP community. 

Adjuvant Therapy Survey Update

Table 1. Patient/family assessed impact of adjuvant therapies reported.

Therapy	Users	No	Improve	Comp	Partial
I3C/DIM	133	61	72	27	45
DIM Ý	7	2	5	1	4
IFN	61	26	35	5	30
Acyc	31	20	11	4	7
PDT*	19	13	6	1	5
Retin	16	10	6	0	6
Mumps	15	6	9	3	6
Cidofovir	20	2	18	4	14

^Ý In most cases the patient/parent has not specifically noted whether they are using I3C or DIM. Please help us assess the impact of DIM vs. I3C by including the specific name of the product that you are using.

Experimental therapies for which the RRPF has no documented patient supplied statistics:

Cimetidine (Tagamet)

HPV Vaccines

Omega-3 Fatty Acids (Fish Oil)

Some notes regarding the above table:

The therapies are abbreviated as follows, I3C/DIM = indole-3-carbinol (I3C) or Diindolylmethane (DIM), IFN = interferon, Acyc = acyclovir, PDT = photo dynamic therapy (*thus far only 1 patient has reported who has used the new agent mTHPC and they have indicated a complete response) , Ribvrn = ribavirin, Retin = retinoicacid or accutane, Mumps = mumps vaccine. In the category of other therapies used, improvement has been noted using the following treatments: Echinacea and Thuja (homeopathic anti-virals), a mixture of vitamins including vitamin C and vitamin A, ShapeRite immune formula, topical 5-flourouracil (5FU), bleomycin and cobalt. (Please see the I3C Update in this issue and previous newsletter issues, regarding side effects for some of these treatments.)

Finally, we continue to remind our readers that these results are based on patient perspectives. Although the survey encourages objectivity and quantitative assessment as much as possible, these analyses cannot replace well-designed clinical trials and research. Furthermore, since sample sizes are generally small and no statistical significance tests have been applied to data in the above table, one must interpret these numbers cautiously, especially when considering the natural variability of RRP. However, we do hope that this information can provide some guidance for those patients seeking adjunct therapies as well as those pursuing RRP related research.

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For background information about the impact of indole-3-carbinol (I3C) on estrogen metabolism and how this subsequently may act to reduce the growth rate of respiratory papillomas, see the RRP Newsletters Fall 93 through Fall 94 and Fall 97, Winter 2000-01 for DIM, as well as Bradlow et al., 1996 J. of Endocrinology 150, S259-S265; Newfield et al., 1993, Anticancer Research 13, 337-342.

News About Phytosorb-DIMÒ and RRP

By Michael A. Zeligs, M.D.

New Scientific Studies Support Phytosorb-DIM Use

Phytosorb-DIMÒ is the only formulation of pure diindolylmethane with proven absorbability. As presented at the recent American Association of Cancer Research (AACR) meetings, there is evidence for increased action of the Phytosorb-DIM formulation compared to unformulated, generic diindolylmethane (1). Case reports demonstrating benefits of Phytosorb-DIM in human papilloma virus (HPV) related conditions were also reported. The presence of HPV in laryngeal tissue and its contribution to Recurrent Respiratory Papillomatosis (RRP) is well documented. The reported conditions included cases of cervical dysplasia, genital warts, and common skin warts. Other researches at the AACR meetings presented additional results using diindolylmethane, confirming its direct activity to promote programmed cell death or "apoptosis" in HPV infected cells (2). Together with recent publications demonstrating the direct action of diindolylmethane as a trigger of apoptosis (3), and further evidence that diindolylmethane is the active metabolite of indole-3-carbinol (I3C) (4), there is growing evidence to include Phytosorb-DIM as a nutritional supplement to help in the control of RRP.

So, the new evidence is that Phytosorb-DIM, in addition to promoting healthy estrogen metabolism, may directly contribute to elimination of HPV infected cells. Localized infection with HPV is a primary contributing process to papilloma growth in RRP. Decreased apoptosis in HPV infected cells has been directly related to the presence of the virus (5), and diindolylmethane may help to restore this process and eliminate HPV infected cells. For this reason, BioResponse, LLC, the originator and manufacturer of Phytosorb-DIM, suggests a higher daily dose range of 8-10 mg/kg for a few months to take advantage of any apoptosis promotion, and then returning to the typical 5 mg/kg/day supplement dose. This may be of particular interest to individuals with RRP requiring frequent surgeries. Phytosorb-DIM can be taken either in a single daily dose with breakfast, or divided, taking half with breakfast and the second half with dinner.

Can Headaches be Associated with Phytosorb-DIM Use.

Two individuals using Phytosorb-DIM have reported headaches associated with its morning use. These individuals were taking a single dose of 8-10 mg/kg/day with breakfast and described headaches that were no longer experienced when Phytosorb-DIM was stopped. These reports are rare and may relate to interaction of the diindolylmethane from Phytosorb-DM with caffeine from morning coffee or tea. Caffeine requires the same cytochrome enzymes for its metabolism as does diindolylmethane, so the combined use may result in higher than typical caffeine levels and an associated caffeine-related headache. For coffee and tea drinkers taking Phytosorb-DIM who experience headaches, it may be better to take Phytosorb-DIM with the evening meal.

Phytosorb-DIMTM products containing DIM are available from:

BioResponse

L.L.C. at P.O. Box 288

Boulder, CO 80306

Email at etzeligs@bio-response.com

303-447-3841 - Telephone; 303-938-8003 - Fax

Credit card orders (Visa and MasterCard) are being accepted

Phytosorb-DIM is available in two forms:

1. Phytosorb-DIM Capsules; 150 mg; 60 capsules per bottle or 75 mg; 90 capsules per bottle.

2. Phytosorb-DIM Flavored* Sprinkles; 9.0 grams per bottle with directions indicating dosage per teaspoon.

At the suggested dosing below, 1 bottle should provide a two-to-four month supply for a child about 50 lbs.

* Available in orange as well as chocolate flavors.

Shipping : US priority mail ($3.20 up to 2 lbs.) , or global priority : small envelope ($5.00 up to 4 lbs; large envelope flat rate $9.00 up to 4lbs.)

BioResponse has reformulated its "Sprinkles". These new formulations require lesser amounts of the powder to deliver the increased suggested dose. Detailed dosing instructions are included on the bottle label. Guidelines for children are as follows:

Weight in Pounds (lbs)

Amount of Sprinkles in Teaspoons (tsp.) up to 25 lbs. 1/8 tsp 25 to 50 lbs 1/4 tsp, 50 to 75 lbs 3/8 tsp, 75 to 100 lbs 1/2 tsp 100 to 150 lbs 3/4 tsp

(Please consult your doctor, especially for young children.)

Call or e-mail for pricing

Special Note: Unlike I3C, Phytosorb-DIM does not require activation by stomach acid. Individuals who use antacids or H2 blockers like Zantac can take Phytosorb-DIM.

For scientific inquiries contact Michael Zeligs, MD at zeligsmd@bio-response.com

I3C may be purchased from:

Theranaturals Inc.

PO. Box 344

Orem UT 84059-0344

e-mail: theranat@itsnet.com

(801)224-8893 - Telephone; (801) 226-6064 - Fax

www.theranaturals.com

[Credit card orders may be placed by phone, fax, web or e-mail]

Theranaturals I3C product pricing as of 9-1-99 (includes shipping via USPS priority mail):

1 bottle - 100 capsules @ 100 mg -$20

3 bottles - 100 capsules @ 100 mg - $55

add $16.00 to above prices for Fed X shipping.

Kronos Pharmacy

3675 S. Rainbow Blvd, #103

Las Vegas NV 89103

Tel: 1-800-723-7455

Local: 702-873-8455

Fax: 702-873-6845

www.kronospharmacy.com

[Credit card orders may be placed by phone, fax, or web ]

For more detailed information ask to speak with Richard Fura.

Kronos Pharmacy I3C product pricing as of 9-1-99:

1 bottle - 100 capsules @ 400 mg - $59.50 + shipping

1 bottle - 100 capsules @ 200 mg - estimated ~ $33.95 + shipping

SHIPPING: UPS 3rd Day Service ($5.00) or Airborne Overnight ($8.00)

Approximate dosing information is based on preliminary results of Dr. Leon Bradlow's estrogen metabolism studies, as follows:

Estimated dosages - Adults approx. 400 mg, Children (under 50 lbs.) 100 - 200 mg

The digestive process is important to properly break down I3C (see RRP Newsletter - Spring 94 ). In this regard, try to avoid taking antacids and it is probably best to take I3C at mealtime. It has also been suggested that taking ascorbic acid (vitamin C) along with I3C will produce ascorbigen, which some investigators (Preobrazhenskaya, et al., 1993, Food Chemistry, 48,48-52) speculate may be an even more important anti-carcinogen than I3C.

If you do not appear to be responding to I3C, you might want to give DIM a try.

Finally, no matter what product one is using the best way to extend the shelf life is to keep them in a cool dark location such as the refrigerator.

I3C/DIM reported side effects:
• Occasional gastro-intestinal upset
• A couple of instances of dizziness

I3C/DIM and bone density:

To date four RRP patients who are using I3C and DIM have reported varying degrees of low bone mineral density (BMD), while at least the same number have reported normal BMD test scores. Unfortunately, in none of these cases was a baseline BMD taken before the I3C/DIM therapy began, so it is impossible to say that I3C/DIM is solely responsible. Furthermore, in a study sponsored by the RRPF it was shown that I3C did not cause bone loss in mice (see summer 2000 issue of the RRP Newsletter). Nevertheless, the possibility still exists that I3C or DIM could result in some of the adverse effects associated with less estrogen such as osteoporosis in humans. After consultation on this subject with Dr. Clark Rosen, the RRPF recommends the following:

1. All new patients starting I3C or DIM should have a baseline dexa scan and follow-ups at 3 and 6 months.
2. Others already taking I3C or DIM should still have a dexa scan test.
3. Please report results of the dexa scan (along with I3C/DIM dosage, your age and weight) to the RRPF including comparisons with normative data where available. This is best done via comments in the online patient survey form or an email to rrpf@rrpf.org.
4. For those already on I3C with additional concerns, consultation with a bone specialist (pediatric in the case of children) is probably the best way to proceed.

We are continuing to follow patients in our PDT study, using the photosensitizer Foscan. The results of this ongoing study are given below.

All of the patients enrolled in the study have moderate to severe disease (requiring surgery at least 3 times a year). Therefore, they are not likely to go into remission spontaneously. Eighteen patients have been enrolled and 15 have been treated with PDT. The Foscan study now includes a control group, with valuations at the same frequency as the PDT group (every three months). The control patients receive PDT if they wish after the control period of 15 months. Three control patients have not yet been treated with PDT. Eleven of the PDT patients have been followed for more than one year after treatment. There was no reduction in papilloma growth at 3 and 6 months after PDT, and most patients actually showed increased regrowth. However, between 9 and 11 months after treatment, there has been a dramatic improvement in most patients. Six of the ten patients with laryngeal disease (60%) were disease free at 12 months and one had improvement greater than 50%, when the amount of papilloma at each surgery was measured. Three patients showed only minimal improvement. Two of three patients with tracheal disease had marked improvement at one year and one was free of tracheal disease at 25 months after treatment. These results were markedly better than our earlier PDT studies with the photosensitizer DHE, where only 3/50 (6%) of patients achieved complete remission and 50% showed no significant improvement. Of the four control patients with data for more than one year of evaluation, none are free of disease. This increases the likelihood that the remissions seen in the 6 treated patients are due to the treatment. Long term response is still difficult to predict. We do know that 2 of the patients who were in remission had a small recurrence after 3-4 years, but do not know whether they will continue to recur every few years or not. Long term studies of the patients will continue to answer this question. We do know that PDT with Foscan, like DHE, does not eliminate the latent (silent) virus, that all papilloma patients carry in their throats even if they are free of disease. We still do not know why PDT with Foscan has such a delayed response, or why some patients did not improve. The percentage without improvement is similar to other experimental therapies, including indole-3-carbinol/DIM and cidofovir. However, we are very encouraged by the fact that more than 70% of the treated patients either went into remission or markedly improved. Our preliminary data suggests that there is an improved immune response to the virus in those patients that respond, and the way in which the immune system deals with RRP in general is being actively studied by our group

Science & Research Activities

A study in children with Recurrent Respiratory Papillomatosis (RRP), sometimes called Juvenile Onset Respiratory Papillomatosis (JORP), is being conducted at approximately 9 medical centers in the United States. Safety and effectiveness (how well the drug works) of study drug injections given monthly for 3 months will be assessed in treating RRP. Standard surgical care will continue throughout the trial and there will be 12 scheduled clinic visits over 60 weeks. The trial is designed to assess whether treatment with the study drug (HspE7) will delay the next required surgical intervention.

Nearly 30 patients have been recruited for this study meeting the following criteria:

1) Patients between 2 and 18 years old with documented RRP

2) Has had at least 3 prior surgeries for RRP

3) Free of life-threatening or serious diseases (other than RRP)

4) Females must not be pregnant or breast feeding

5) Must not have an illness or taking medications that compromise the immune system

6) Must not have a history of radiation therapy to the respiratory tract

7) Must not receive medicines to treat RRP therapy within at least 30 days of entry into the study

Location of participating medical centers:

Little Rock, AK

Birmingham, AL

Jacksonville, FL

Iowa City, IA

Cleveland, OH

Minneapolis, MN

Dallas, TX

Norfolk, VA

HspE7 is produced by Stressgen BioTechnologies

Stressgen Contact Information:

www.stressgen.com CanadianOffice: #350 - 4243 Glanford Avenue Victoria, BC Canada V8Z 4B9 Phone: (250) 744-2811 Toll Free: (800) 661-4978 Fax: (250) 744-2877

Principal Executive Office: 4445 Eastgate Mall, 2nd floor San Diego, CA 92121 USA

Telephone: (858) 812-5616

Brian J. Wiatrak, MD, FAAP,FACS

Juvenile-onset Recurrent Respiratory Papillomatosis (JRRP) is a disease in which tumors may grow inside either the respiratory or digestive system. JRRP is the most common

benign neoplasm in the larynx and second most common cause of hoarseness in children.

The Centers for Disease Control and Prevention tracks approximately 500 children in its national Registry of Recurrent Papillomatosis. Our Pediatric Otolaryngology Practice cared for approximately 90 children with Papillomas.

JRRP children and their families have described to our airway team situations that have demonstrated bias. We wanted to learn more about how wide spread this problem might be and develop methods to assist these families in dealing with bias situations.

This parental survey and development of the educational materials were supported by a grant from the RRP Foundation.

The purpose of this study was to determine parental perceptions of bias against their child diagnosed with JRRP. A descriptive study was developed and questionnaires were

mailed to families of children that have been treated for papillomatosis by our team.

Surveys asked the question "Has your child or family ever been treated unfairly because your child has papillomas?" In addition, parents were asked to give specific examples relating to child care, school system, family members, extended family / friends, health care professionals and insurance companies.

Approximately one-fifth of the questionnaires returned responded that their children and or families have experienced bias. If one child or family experienced unfair treatment

because of the child’s diagnosis of JRRP we were committed to the development of educational / supportive materials. A family support tool was developed including all six areas of bias identified and is available to families and support groups.

Future implications may include further development of educational / supportive materials for families and materials directed toward child care agencies, school systems, health care professionals and insurance companies. Future research would be a multi-institutional study to survey parental perceptions of bias, against their family and child diagnosed with JRRP.

Recurrent respiratory papillomatosis(RRP) is a disease in which tumors grow inside the larynx, primarily on the vocal cords, but sometimes spreading to the trachea and even the lungs. It affects both children and adults. Research has determined that the Human Papilloma Virus (HPV), is present in these respiratory tumors. These growths are often associated with two specific types of the virus (HPV6 and HPV11) which are also found in genital and cervical warts.

There is no known cure for RRP, with CO2 laser surgery under general anesthesia being the accepted method of controlling these growths. If left untreated these respiratory tumors will continue to grow, blocking the patient’s airway with suffocation being the likely result.

The Recurrent Respiratory Papillomatosis Foundation* was created to provide patient/family support, serve as an information resource for patients and practitioners, promote public awareness, and aid in the prevention, cure and treatment of RRP by encouraging and participating in promising RRP research studies..

The RRP Foundation is primarily focusing on the networking of the RRP community, including patients (both juvenile and adult), families, medical practitioners and researchers. The nuclei of the network is the RRP Newsletter. and the RRPF website. The newsletter and website include support network information, statistics and activities, individual RRP patient case histories, developments with regard to RRP (i.e., treatments and research directed to both practitioners and patients), plus any additional information that might help further understanding and/or awareness with regard to this disease.

The concerns and objectives of the RRP Foundation are as follows:

The RRP Foundation is a completely volunteer organization, comprised of RRP families, practitioners researchers and friends. We very much appreciate your help and support in creating greater awareness so that RRP gets the attention it deserves. If you would like more information about Recurrent Respiratory Papillomatosis or would like to donate and become a subscriber to the RRP Foundation, please call or write the RRP Foundation, c/o Marlene and Bill Stern, P.O. Box 6643, Lawrenceville, NJ 08648-0643, Tel. (609-530-1443, 258-2751), or contact any of our other information/support centers.

Main Info. Center and Northeast

Marlene and Bill Stern

P.O. Box 6643

Lawrenceville, NJ. 08648-0643 (609)530-1443

Bill’s e-mail: bills@rrpf.org or rrpf@AOL.com
Marlene’s e-mail: marlenelin@aol.com

Mid-West

Diane Burke, R.N
University of Iowa Hospital, Dept. of Otolaryngology
200 Hawkins Drive

Iowa City, Iowa 52240-1009 (319)356-1765
diane-burke@uiowa.edu

Southeast & Florida

Wendy Bodner

4800 S.W. 64th Ave., Suite 110

Davie, FL 33314-4449 (305)581-3400

e-mail: wsbcpa@email.msn.com

West Coast & California

Susan and Bob Spock

1553 Via Allondra

San Marcos, CA 91606 (760)744-5022

e-mail: sspock@mail.adnc.com

Asia

Susan and Henry Woo

101 Repulse Bay Road
Apt. A3/1st floor, Hong Kong 852-2812-7379
e-mail: writeushere@aol.com

Europe
Jan Schneider-Eicke, MD
Sonnwendstr.19
82152 Krailing, Germany 49-89-85661486
e-mail: nuklearmedizin@klinik-schindlbeck.de

California

Cheryl Downey
2520 Pearl Street

Santa Monica CA 90405 (310)581-6690
e-mail: cheryl_downey@paramount.com

Georgia

Bill Widmayer

744 Hickory Ridge Rd. SW

Lilburn, GA 30047 (404)313-8965(days); (770)921-9497

e-mail: widmayer@mindspring.com

Christina Lancaster

186 Pine Knoll Lane

Eatonton, GA 31204 (706)485-1016

e-mail: ChristinaYL2001@cs.com

New York

Barbara Kotler
2545 Navy Pl.
Bellmore, NY 11710 (516)679-5160

Oregon

E. Susan Bates
614 W. Second St.
Medford, OR 97501 (541)779-9233

e-mail: esbates@hotmail.com

South Carolina & North Carolina

Tami Shirley

206 Charlwood Rd.
Irmo, SC 29063-2303 (803)487-6484

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Please find enclosed my tax deductible donation of $_________, to help support those patients and families trying to cope with Recurrent Respiratory Papillomatosis and to help find a cure for this disease.

I would like to become a new subscriber ___ , continue my subscription ___ , to the RRP Foundation:

RRP Newsletter - Professional/Corporate (sugg. donation $25) _____. Individual (sugg. donation $15)______

Newsletter and RRP Reference Service - Professional/Corporate (sugg. donation $40) _____.

Individual (sugg. donation $25)______

Name ______________________________________________________________________________________________

Address _____________________________________________________________________________________________

_______________________________________________________________________Phone ________________________

e-mail:__________________________________________________________________Fax _______________________
Please make checks payable to: RRPF, send to: RRP Foundation P.O. Box 6643, Lawrenceville, NJ 08648-0643

The RRPF is a 501 (c) (3) non-profit corporation as determined by the Internal Revenue Service. Fed. Id #: 521798693

RRP Foundation
P.O. Box 6643

Lawrenceville NJ 08648-0643