Vol. 10 No. 2

An RRP Foundation Publication

2001/2002 Winter

___________________________________________________________________________________________________________________

Contents

• Opening Comments - p1
• RRPF 1^st Annual Hockey Night fundraiser - p1
• RRP researcher position - 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
  • Proposed RRP Focus Session - p4
  • International Papillomavirus Meeting - p4- 5
  • Highlights of the ESPORL 2001 meeting - p5
• Adjunct Therapy and Protocol Update - p5 - 7
  • I3C/DIM - p6
  • Phytosorb-DIM^TDose Review - p6
  • I3C/DIM & Bone Density - p7
• RRP& Voice - Vocal Hygiene Tips - 7- 8
• Science & Research Activities - p8- 9
  • HspE7 Clinical Trial for RRP - p8
  • I3C/DIM suppresses HPV oncogenes - p9
• Patient Update - p9
• Support/Subcriber Info - p10

Holiday Greetings

We are pleased to present the 2001/2002 winter edition of the RRP Newsletter. While there are many interesting topics in this newsletter, we would like to point you to the recent RRP presentation at the International Conference on Pediatric ORL in Graz, Austria. The presentation was given by RRPF’s European coordinator, Jan Schneider-Eicke, MD., and generated a great deal of interest in the European Community. This presentation was a great success and we are very appreciative of Dr. Schneider-Eicke’s time and effort in representing the RRPF at this meeting.

We would like to wish everyone and their families a Happy and Healthy Holiday Season.

Chris Neuberger Bill and Marlene Stern

Cneuberger@eti1.com bills@rrpf.org

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.

First Annual RRP Foundation Hockey Night at the MCI Center in Washington D.C. Saturday, January 19, 2002

Enjoy the Washington Capitals vs. Vancouver Cunnucks
Proceeds will go to the RRP Foundation. Tickets are $35 per person and are available through the RRPF Fundraising
Coordinator, Ed Weiner.  For more information contact him at: (703) 691-1922 or (703) 273-9500

Capitals game begins @ 7:00 pm .A bonus game follows the Caps game. You can move down to the lower level seats and get to see Ed Weiner "in action" as he plays for TEAM USA vs.
DEVILS of the Fairfax Adult Hockey League.

The position is for a PhD with a proven track record of published expertise in animal virology who would be interested in heading up a lab to study the basic science aspects of RRP, with a goal of converting this knowledge through transnational mechanisms into treatment modalities for this disease.

The individual would hold a joint appointment at the University of Tennessee Memphis School of Medicine and at St. Jude Children's Research Hospital.

CVs and a personal statement of interest in further information should be forwarded to Dr. Jerome W. Thompson E-Mail JWThompson@UTMEM.Edu

Many thanks to all who participated in the RRPF’s first ever "Virtual Golf" fundraiser, organized by Ed Weiner.

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

101 Repulse Bay Road

Apt. A3/1st floor

Hong Kong

852-2812-7379

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 enclosure 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

Chris Neuberger
Jennifer Woo

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

*** Introducing our new ***

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 Toni and Dale 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.

Kim from Maryland, who is now 14 years old, is now in remission after a very aggressive history. Please read more about Kim in the patient update on page.

Bill from California, who is now 52, first developed hoarsness at the age of 48 and was diagnosed with RRP shortly thereafter. He had 3 surgeries in about 6 months time, but has not had a surgery since. He credits DIM along with a regimen of vitamins for helping to put him in remission (although currently Bill has stopped taking DIM).

Others still in remission (who we were able to contact) include: Ten year old Ariel and Eleven year old Jonathon from California; 27 year old Julie and 28 year old Steph from Florida; Mike from Georgia at age 49; William age 77, from Illinois; Cara from Michigan at age 19; Ten year old John David from Missouri; Leah from New Hampshire, age 22; 12 year old Lindsay and 22 year old Christina from New Jersey; Joe from Ohio at age 34; 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 about 590 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 28 patients from 13 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 187 subscribers with over 1400 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", continues to be a valuable resource to the RRP community. Intended for use by patients, family members and professionals dealing with RRP, as well as related diseases and conditions, there are currently 187 registered members. Over the past six months, there have been approximately 750 messages posted to

the list. This low volume (~2-3 messages per day) 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 (e-mail: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". 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.

Some of the most significant community interaction on the list, and often the most touching, are those messages from newly diagnosed RRP patients, or parents of new patients, who simply say, "my goodness, now what do I do now?". Through the mailing list, these folks quickly gain access to the cumulative technical knowledge and experience of the whole of the list. And, more importantly, they gain access to a human support link that can help these often anxious and bewildered people in understanding that this disease can be managed. Other significant threads on the message board over the past six months have included discussions of bone density sensitivity to DIM, the relationship of allergies to RRP, issues and experiences with insurance coverage, adjunct therapy use, dosage, and success, inquiries regarding finding experienced RRP health care providers, strategies for voice rest after surgery, surgical techniques, timing of surgeries, and the strength demonstrated by the little ones that are so often significantly impacted by this disease.

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 486 to 547 for tables 1-3.

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

	Females	Males
All Ages	243	304

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

Age Groups	Females	Males	Total
Under 10	50	50	100
10-20	67	57	124
20-30	25	17	42
30-40	39	44	83
40-50	19	38	57
Over 50	24	56	80

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

Age Groups	Females	Males	Total
Under 10	165	151	316
10-20	14	7	21
20-30	23	34	57
30-40	12	43	55
40-50	11	30	41
Over 50	6	15	21

Table 4. Distribution of respiratory papilloma sites of involvement based on responses from 367 patients.

Site:   sitesite	J-O	A-O	Total patients
above cords	112	48	160
at cords	193	151	344
below cords	91	41	132
tracheal	47	16	63
bronchial	26	7	33
lung	18	4	22

Table 5. Distribtion of surgeries for RRP

	JO-RRP	AO-RRP	ToT
1-10	64	102	166
11-25	46	36	82
26-50	34	19	53
51-75	15	2	17
76-100	17	0	17
>100	22	3	25
>200	5	2	7
tot responses	203	164	367

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	71/71	88/101
No	115/64	88/44

RRP National/ International News

In conjunction with the American Academy of Otolaryngology 2002 annual meeting, the RRP Foundation is proposing to sponsor a meeting where RRP patients/families, clinicians and researchers can get together to discuss current issues regarding RRP. I am hopeful that we can have as successful a meeting as the previous session held on 23 September 2000, in Washington, D.C. We are tentatively proposing to hold this meeting on Saturday, 21 September 2002. Please let us know of your interest (bills@rrpf.org). As arrangements are finalized, further details will be posted to the RRPF website and included in the next newsletter issue (Summer 2002). We will look forward to seeing you in San Diego.

……………………………………………………………………

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.

This year in July the European Society for Pediatric ORL (ESPORL) held the first biennial meeting in Graz/Austria.

For the first time the organizing committee had dedicated two sessions exclusively to RRP. The RRP Foundation was invited to participate in these sessions, to present the information about the organization and to demonstrate its activities and objectives. The RRPF was represented by its European support coordinator Dr. Jan Schneider-Eicke, the talk given was prepared by Bill Stern.

The presentation of the RRPF was well appreciated and followed by a lively discussion. This discussion focused on the impressive collection of data regarding patients and therapies, the overall opinion was that similar data should be collected in Europe in cooperation with the RRPF. Although there was no major disagreement regarding the forms of treatment, it was agreed that a comparison between the U.S. and Europe might be interesting. Furthermore the need for an organization giving similar support to European RRP-patients was stressed.

The other talks focused on the histopathological bases of RRP, the classical surgical management, special anesthesiological techniques (i.e. Jet-Ventilation), methods of endoscopic evaluation and newly developed forms of treatment.

Prof. W. Bergler from the Department of Otorhinolaryngologie, University of Mannheim, Germany gave a very interesting overview of commonly used treatment strategies including laser, interferon and cidofovir. Furthermore Dr. Bergler has quite extensive experience using Argon-Plasma-Coagulation. In his opinion this newly developed technique has very promising results especially in the treatment of tracheal lesions since it does not tend to create extensive scarring as the laser often does. More experience is necessary to evaluate the use of this method in the removal of laryngeal papillomas.

Another very interesting presentation was given by Prof. W. Wellens, MD, from Belgium, who was among the first researchers using intralesional Cidofovir in the treatment of RRP. His talk was mainly based on his publication in the Journal of Virology in 1998 stating impressive results in controlling the disease, sometimes even curing it. In a private conversation after the session he stated that his follow-up studies had even better results with no side-effects and that on completion of the present works a follow-up article would be published.

In conclusion the congress was a big success in promoting the RRPF in Europe, various colleagues asked to be put on the RRPF mailing-list. The collection of data from Europe will be intensified with the goal to establish a database comparable to that in the U.S. In close cooperation with the RRPF board, it is proposed that a similar organization be established in Europe.

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. 

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

Therapy	Users	No	Improve	Comp	Partial
I3C/DIM	132	60	72	27	45
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	19	3	16	4	12

We would like to try to assess the efficacy of I3C vs. DIM by getting a detailed breakdown from those I3C or DIM users regarding which product they are taking, dosage information and whether they can clearly assess the impact. Although many patients indicate that they are using DIM, to date only 5 people have specifically noted on their patient survey forms that they are taking DIM and that they feel confident of making a response assessment. Of these 5 cases, 4 have indicated some positive impact and 1 indicated no response.

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.

……………………………………………………………………

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.

Phytosorb-DIM is a highly absorbable formulation of pure diindolylmethane, found naturally in cruciferous vegetables and formed from precursor indole-3-carbinol (I3C) during digestion. With current use, Phytosorb-DIM promotes a healthy estrogen metabolism increasing daily production of protective 2-hydroxy estrogen metabolites. Studies have now shown that diindolylmethane itself, independent of estrogen metabolism, is a highly active substance directly promoting apoptosis, or "programmed cell death", in various abnormal cells.¹ These include cells infected with the Human Papilloma Virus (HPV).² Localized infection with HPV is the primary contributing process to papilloma growth in Recurrent Respiratory Papillomatosis (RRP).

Phytosorb-DIM has been used as a dietary supplement by a large number of children and adults with RRP since 1998. Reported benefits have included lengthening of intervals between surgical removal of papillomas and numerous cases of long-term, surgery-free remissions. BioResponse, LLC, the manufacturer of Phytosorb-DIM, suggests a daily dose range of 5 &emdash; 8 mg/kg (1 kg = 2.2 lb). Individuals with RRP requiring frequent surgeries who are using the product at the lower dose of 5 mg/kg/day might benefit by increasing the dose to 8 mg/kg/day. 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.

Individuals taking Phytosorb-DIM and interested in higher dose use should contact BioResponse directly. E-mail inquiries to zeligsmd@bio-response.com are preferred, or call 303-447-3841. Spanish is spoken by the BioResponse staff.

References:

1. Hong, C, Firestone, et al., "Induction of apoptosis in MCF-7 and MDA-231 human breast cancer cells by 3,3'-Diindolylmethane (DIM)", Presented at Experimental Biology 2001, March 31-April 4, 2001, Orlando, Florida.

2. Carter T, Liu J, et al., "3,3"-Diindolylmethane, a chemopreventive agent for HPV-associated tumors, suppresses expression of HPV oncogenes in cervical cancer cells", Presented at the 19^th International Papillomavirus Conference, Florianopolis, Brazil, September, 2001.

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 about 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. 

RRP & Voice

•  
• Avoid speaking too loud or too long

•  
• Avoid yelling/screaming

•  
• Avoid making noisy sounds with your voice

•  
• Maintain adequate hydration

•  
• Avoid clearing your throat/coughing, if possible

•  
• Avoid whispering

•  
• Be aware of stress and extra muscle tension, overall

•  
• Focus on breathing from the diaphragm

• Treat reflux/environmental allergies

•  
• Do not smoke/avoid second-hand smoke

NOTE: For parents, encourage "good" vocal behaviors and try to serve as a model for your child. Practice teaching your child "tensed" versus "relaxed" voice. Try labeling situations that may require more effort and talk about ways to alter the environment or compensate without increasing strain. Seek guidance from a speech-language pathologist.

Science & Research Activities

[The Following is a press release from 19 November 2001 announcing a clinical trial using the HPV vaccine HspE7 to treat RRP:]

The Company is Evaluating the Potential of HspE7 to Treat

Genital Warts of the Upper Airways

Victoria, B.C., Canada - Stressgen Biotechnologies Corporation (TSE: SSB) announced today that it has initiated its pilot Phase II open label trial in pediatric patients suffering from a human papillomavirus (HPV)-related disease called recurrent respiratory papillomatosis (RRP). In the U.S., there are about 2,000 new cases each year of pediatric respiratory papillomatosis. The Company was granted orphan drug status for HspE7, a novel immunotherapeutic, from the United States Food and Drug Administration (FDA) in March of this year. The trial will involve approximately 27 pediatric patients that currently require frequent surgery, and will be conducted in multiple centers in the U.S. The dose will be 500 mcg administered three times at monthly intervals. The endpoint for the trial will be an increased interval between clinically required surgeries. Data from this trial could be available as early as 2002. "Currently the only treatment available for RRP is surgery," said John R. Neefe, M.D., Vice President, Clinical Research and Regulatory Affairs for Stressgen Biotechnologies. "There are no approved drugs or immunotherapies. The average pediatric patient has about five surgeries per year and some children tragically have hundreds of procedures in their lifetimes."

"Despite the best that current medicine has to offer, the papillomas recur relentlessly and the condition of the disease can be grueling and prolonged," said Daniel L. Korpolinski, President and Chief Executive Officer of Stressgen Biotechnologies. "There is a tremendous need for new treatment options in this population. Because HspE7 has demonstrated activity in other conditions caused by the HPV subtypes 6 and 11 associated with RRP, it is very important to test HspE7 in this disease. Considering HspE7’s orphan drug status in this indication, RRP may provide the shortest route to market for Stressgen."

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[In a follow-up telephone interview with Peter Zarevics at Stressgen, the RRPF learned the following additional information:]

This trial is designed to be fairly small with less than ten medical centers participating and an anticipated enrollment of about 30 pediatric patients between the ages of 2 and 18. The enrollees must have a fairly aggressive, well established surgical history with surgical intervals averaging less than 12 weeks. This is not a double-blinded study with one group getting a placebo, the enrolled patients surgical history will serve as the control. RRP patients/parents seeking to be enrolled should talk with their doctors.

The protocol involves 3 subcutaneous injections four weeks apart. The time scale for results from this trial, which includes a significant follow-up period, is expected to be at least a year from the start. As relevant information becomes available, the RRPF will keep the RRP community informed.

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

[The following abstract is from a presentation made by Dr. Karen Auborn at the HPV meeting held in Florenopolis, Brazil this past September (2001). It describes experiments with HPV cells in vitro. DIM is applied to the cells and tests indicate that there is enhanced expression of a number of genes which results in less growth of the papillomavirus. This reduced expression of HPV is independent of the effect that DIM has on estrogen metabolism.]

Long Island Jewish Medical Center, The Long Island Campus of Albert Einstein College of Medicine, New Hyde Park, NY 11040

Indole-3-carbinol (I3C) and its active dimer diindolylmethane (DIM), compounds from cruciferous vegetables, have recently become a benign treatment for precancerous lesions of the cervix and laryngeal papillomas. I3C/DIM are antioxidants, alter estrogen metabolism, and induce detoxifying enzymes, growth arrest and apoptosis. This study was to understand in a comprehensive way which genes are altered in response to I3C/DIM, to provide insight into these multiple antitumor activities. Using microarray profiling &emdash;both oligo and cDNA methodology, we evaluated changes in gene expression in the cervical cancer cell lines-C33A and CaSki- after treatment with 100 microM DIM. Multiple analyses (3 by oligo method and 2 by cDNA method) were done after treating C33A cells for 6h. Additional analyses were done after 4h and 12h treatment and with CaSki cells treated for 6h. For a subset of genes, Western analysis was used to confirm that protein content correlated with increased expression. RNase protection and reporter gene assays were used for functional assays of HPV expression. Many genes (114 up and 14 down) coding for transcription factors, proteins involved in signaling, stress response and growth were consistently transcriptionally altered by DIM. Results were comparable between the C33A (without HPV sequences) and CaSki (with many copies of HPV16). A subset of genes, namely GADD153 (induced about 50 fold), NF-IL6 (alias c/EBP beta), c/EBP gamma, ATF3 and cJun &emdash;all leucine zipper proteins-, were highly induced by DIM. Homo and heterodimers of the leucine zipper proteins impact transcription of relevant genes, and leucine zipper proteins induced by DIM should affect transcription of HPV oncogenes known to depend on AP1 and c/EBP families of proteins. We, therefore, determined that DIM not only suppressed transcription of reporter genes driven by HPV11 and HPV16 promoters, but also endogenous transcription of HPV16 in CaSki cells. Ongoing experiments using expression vectors confirm that some of the leucine zipper proteins induced by DIM suppress HPV oncogene transcription. We confirmed that a number of genes that were rapidly and highly induced down regulated transcription of HPV oncogenes. This mechanism provides an additional pathway by which dietary I3C/DIM prevents HPV-related diseases. Additionally, the battery of genes induced by DIM resemble those induced by proteosome inhibitors and endoplasmic reticulum stress, pointing to an early effect of DIM on protein homeostasis as a potential mechanism by which it initiates at least some of its multiple anticancer activities.

RRP Patient Update

Kim Randall was first diagnosed with RRP at the age of two, her first surgery was in August of 1989. Since that time Kim has had 88 surgeries. At times Kim was having surgery more frequently than every two weeks. From 1989 to 1999 she tried several adjunct therapies including I3C/DIM (which did not seem to work well for Kim) and interferon. Despite significant flu-like side-effects, interferon did help Kim for a while, including an 8 month period of remission. But then the interferon lost its effectiveness and by February 1999 her RRP had become quite aggressive again with surgeries every 4-6 weeks. By June 1999 papillomas had spread to her trachea and after consultation with Dr. Clark Rosen, Kim and her parents decided to try the new experimental treatment for RRP, cidofovir. Cidofovir appears to be very effective for Kim. It has been over a year since her last surgery.

Kim’s mom, Renee, says that she was been doing so well with her breathing that she recently tried out for the high school basketball team. She was running laps and working out with the team. It wasn’t easy but she was able to do it without giving up. She would have made the team if she hadn't broken another bone during tryouts (Kim has been diagnosed with osteoporosis). This time it was just a finger that was dislocated and has a splinter fracture down the bone. Apparently when she went to catch a bad pass it hit her hand wrong. In any case, her fighting spirit is still going. She is sure that she will make the team next year.

You can read much more about Kim on her website at: http://members.tripod.com/Kimsstory/index.html

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