Vol. 12 No. 1 An RRP Foundation Publication 2003 Summer
P.O Box 6643, Lawrenceville, NJ 08648-0643

___________________________________________________________________________________________________________________
 
 

This issue of the RRP Newsletter is dedicated to Alexa Rae Phillipakis-Patten, a 3 year old child with RRP who tragically passed away in October of last year. A memorial is included on page 10 of this issue.
 
 

Contents

•  
• Opening Comments - p1
• RRPF Organization Information - p2
• RRPF Publication and Subscription Policy - p2
• RRPF Fundraising Activities - p3
• RRP Remission - p4
• RRP Network/Internet News - p4
• RRP Listserve Highlights - p4
• RRP Patient Statistics - p5
• RRP Meetings - p5-6
• RRP Focus Session 2002 - p5-6
• RRP Task Force - p6
• Adjunct Therapy and Protocol Update - p7-8
• I3C/DIM - p7-8
• Pulse Dye Laser - p8
• Science & Research Activities - p9-10
• HspE7 Phase II trial update - p9
• COX-2 inhibitors for RRP - p9-10
• Genetic patterns and I3C/DIM response - p10
• RRP patient quality of life study - p10
• Memorial: An RRP Tragedy - p10
• Support/Subcriber Info - p11

From the Newsletter Coordinator and Editor
 
 

The RRP Foundation has been supporting and networking the RRP community for more than a decade and wants to continue to be responsive to the needs of the RRP community. In this regard we would appreciate any comments or criticisms you may have regarding the RRPF. The best way to let us know what you are thinking is by email to one of the members of the RRPF Board, i.e., Chris Neuberger, Susan Woo or Bill Stern, (see addresses listed in the section on "Organizational Information".)

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. If you are interested in assisting in any way, please contact Bill Stern (bills@rrpf.org).

We hope you find this newsletter issue to be interesting and helpful. If you have any questions or comments about this issue, please contact the principal newsletter editor, Chris Neuberger (Cneuberger@eti1.com) or Bill Stern.

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 who 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.
 

To physicians and nurses: Please distribute copies of this newsletter to your RRP patients. Please register with the RRPF by completing the Practitioner Questionnaire (online or copy 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

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

Clark Rosen, MD, University of Pittsburgh Voice Center

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

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, advocacy and research
 
 
 

Subscription Policy and Suggested Minimum Annual Donations:
 
 

RRP Newsletter

Professional/Corporate - $25
Individual - $15
 
 

RRP Newsletter plus Medical Reference Service

Professional/Corporate - $40
Individual - $25

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

The RRP Foundation is supporting the efforts of the Cody Pate Foundation to raise funds to help defray travel and some other expenses related to obtaining treatments for RRP. President Lynette Pate is spearheading activities in the Memphis,TN area and Los Angeles, CA in an effort to raise RRP awareness and funds for RRP. For more information contact Lynette Pate at: Buddie4breathing@aol.com
 
 

RRPF Fundraising Coordinator Ed Weiner announces that the 3^rd annual RRPF Hockey night will take place at the MCI Center in Washington D.C. Saturday, January 31, 2004. For more information contact Ed at: eweiner@weinerandassociates.com
 
 

RRP patient and RRP Newsletter editor, Jennifer Woo, will be running in the next Boston Marathon which will take place on Monday, April 19, 2004. She wants to raise money for the RRP Foundation and is asking those who would like to help sponsor her efforts to pledge either an amount per mile (26.2 miles maximum) or a fixed amount for the entire race. For more information contact Jennifer at: jwoo@fas.harvard.edu
 
 
 
 

.......................................................................................................................................
 

I would like to pledge $________________________ in support of Jennifer Woo's efforts to raise money for RRP by running the 2004 Boston Marathon.

You may email your pledges to marathon@rrpf.org or send by regular mail to: RRPF Marathon Fundraiser, PO Box 6643, Lawrenceville, NJ 08648
 
 

RRP Remission News
 
 

!!! Some new additions to our growing list of remissions!!!

Lynn from Alaska,age 55, has had a mild case of RRP, but since she started taking I3C in 1999, she has not required any surgery.
 
 

Talia, age 13, who lives in Colorado who had undergone 30-35 surgeries between the age of 2 and 9, was treated with the Mumps vaccine (Dr. Nigel Pashley's protocol) and has been in remission for 4 years.
 
 

Cody from Nevada who is 13 had 27 surgeries before he went into remission 3 years ago. He gives credit to I3C.
 
 

August who is now 64 and is located in Mississippi, had beeen requiring surgeries about every 6 weeks aaafter an aggressive cidofovir treatment program in Belguim from one of the pioneers in using that drug for RRP (Dr. Wellens), August has been papilloma free for over 2 years.
 
 

RRP Network News
 
 

Our international support network has grown to approximately 650 respiratory papilloma families. Patients range in age from about 2 to 88 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.
 
 

Doctors and nurses treating RRP patients take a few minutes to fill out the practitioner survey form.

You can find the online "patient survey" and "practitioner survey" on the RRPF home page (www.rrpf.org).

Also, we maintain an online library of RRP Newsletter and RRP Reference Service issues plus links with many other sites relating to RRP and much more.

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" continued to be very active over the past 3 months. With approximately 200 subscribers made up of RRP patients, health care providers*, and caregivers*, this low volume list has become a valuable resource for the whole RRP community.

Recent significant discussion topics included: anecdotal experiences with current adjunct therapies and emerging treatments, surgical approaches, and posts by patients and families who have recently begun to deal with RRP.

Some recent posts to the Listserve were from list readers and subscribers who were legitimately concerned about privacy. The RRPF Listserve is hosted by Yahoogroups.com. Anyone on the Internet can read the posts without subscribing to the list. You must subscribe (register) for the service to be able to post messages. While the RRPF, list moderators, and many subscribers acknowledged subscriber concerns about posting personal medical information on the Internet for all to see, the majority of responses to this discussion supported open access to the content of the RRPF Listserve. There was clear consensus that the value of open sharing of RRPF information and interaction among the community outweighed the privacy concerns. In any case, those posting to the Listserve should be aware that posts are readily available on the Internet and will be stored there for the foreseeable future. Subscribers with privacy concerns should not post full names, postal addresses, e-mail addresses, etc.

. If you haven't joined yet, please feel free to do so by sending a blank email to: rrpf-subscribe@yahoogroups.com. More information about the listserve and a complete list archives are available on the Internet/World WideWeb at: http://groups.yahoo.com/group/rrpf. The messages may 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.

* There have been some very helpful and informative posts from a few RRP professionals. We would very much like to encourage RRP professionals to post more regualrly to the listserve.
 
 

RRP Patient Stats
 
 

The statistics that follow are based on RRPF patient 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. (Also, see adjuvant therapy stat on page 7)

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

	Females	Male
All Ages	275	332

 

Distribution of patients based on diagnosis age brackets and sex (sample size = 567)

 Table 2. Birth Statistics from Patient Support Network:

	yes	no	sample size
c-sec (JO)	14	277	291
c-sec (AO)	14	175	189
1st Born (JO)	181	92	273
1st Born (AO)	70	113	183
Adopt (JO)	53	240	293
Adopt (AO)	7	191	198
Mat Age <20 (JO)	55	140	195
Mat Age <20 (AO)	8	104	112

Table 3. Distribution of respiratory papilloma sites of involvement based on responses from 418

patients.

Site:     sitesite	J-O	A-O	Total patients
above cords	135	59	194
at cords	226	173	399
below cords	111	47	158
tracheal	56	20	76
bronchial	28	8	36
lung	22	4	26

 
 
 
 
 
 
 

RRP Meetings
 
 

On September 24, 2002, 50-55 members of the RRP community gathered in a ballroom of the San Diego Marriott Hotel for this year's RRP Focus Session, sponsored by the RRP Foundation, with generous support from the Medtronics Corp. The meeting was held in conjunction with the 2002 Oto. Expo. Presenters and participants included physicians, clinical researchers, patients and their families, with topical emphasis resting mainly on the effects of cidofovir treatments and growing popularity of microdebrider removal of papilloma lesions.

Foundation director Bill Stern opened the seminar with a brief list of Foundation objectives - among them, maintaining the support and information network of the website, email listserve, and family directory; collaboration with the wider scientific community, including participation in meetings and task forces; and enhancing existing databases of RRP information. The RRPF would also further develop its website and fund more research for relevant projects. He did not neglect to mention the potential difficulty of some of these tasks, due partially to the variability in presentation of RRP (i.e., spontaneous remissions and particularly aggressive cases would be hard to track for analytical purposes), but stressed that there may be benefits to examining possible genetic factors influencing the 0.005% appearance rate amongst the 5% of the US population that is suspected of being HPV positive in their respiratory tracts.

Michael Green of the International RRP ISA Center based in Seattle, WA, also lamented the status of RRP as an orphan "backwater" disease, lacking the publicity needed for more extensive research. Citing the charitable nonprofit organization's aims of maintaining an informative website, empowering patients and families, improving RRP treatment and educating the general public about RRP, he declared, "[RRP] is a disease that shouldn't be backwater because fifty million people plus in this country are infected by HPV, which is the virus that causes it." Subsequently, he offered an outline of the predictable course of an RRP patient's diagnosis and treatment pattern &emdash; which, over the span of an adult onset patient's life, could run up bills of up to $650,000. Green also suggested that injury of the vocal cords can often be traced to overaggressive laser therapy by doctors unaware of the dangerous potential consequences of repeated laser use, and sympathized with patients persistent in their search for experienced surgeons. "People often value good doctors," he explained. "Who is good? Who is bad? ... It's not unusual for [patients] to travel hundreds of miles [in search of a good doctor.]"

East Virginia Medical School's Craig Derkay, MD, University of Alabama (Birmingham)'s Brian J. Wiatrek, MD, and San Diego Children's Hospital & Health Center's Seth M. Pransky, MD, each offered responses to Green's discussion of overaggressive laser therapy, presenting results of recent studies focusing on the effects of microdebrider and CO₂ laser treatment as well as the effectiveness of cidofovir. Pransky introduced the general treatment protocol practiced at San Diego Children's, which mainly involves conservative interval debulking of papillomas to maintain an uncompromised airway and acceptable voice quality. Ultimately, the goal is to avoid a tracheostomy that could lead to changes in the cells lining the tracheal mucosa, thereby encouraging seeding of the papillomavirus.

While chemical treatment options range from interferon to DIM to ribavirin, acyclovir and HSP-E7, the predicted success of any of these measures on a patient is, at best, a crapshoot, according to Pransky. Surgical options include removal by laser, microdebrider or steel forceps, with the majority of physicans preferring the laser and microdebrider. In operating suites, the CO₂ laser treatment is still the most widely accepted standard of papilloma management. Its popularity is drawn not only from its familiarity within the ENT community, but also from its precision (rendering it well-suited for small lesion removal), binocular visualization capabilities, and absence of incision-related bleeding during and following the procedure. Its disadvantages, however, can be significant - scarring from thermal injury or overaggressive use, airway fires, ineffectiveness on bulkier lesion masses and the risk of laser plume effects on both anesthetized patient and medical personnel are all legitimate concerns related to CO₂ laser treatment.

These factors may also be influential in the growing popularity of the microdebrider as a papilloma management strategy - an option which, according to Dr. Wiatrek, is also significantly less expensive than the laser to operate. Dr. Wiatrek emphasized the satisfaction of "blinded" parents of 19 patients with active RRP who collectively underwent a total of 32 procedures (18 by microdebrider, 14 with laser). Microdebrider patients reported improved voice quality, although post-operative pain levels remained the same with both devices.

While surgeons must be thoroughly familiar with the device's applications and the appropriate choice of blade type and speed for excision procedures, the micodebrider's effects on laryngeal tissue can be far less traumatic and better suited for peduncular papilloma regions than its laser counterpart. Some of the drawbacks associated with microdebrider treatment include sessile lesions, decreased visualization, bleeding from the blade's incisions and the learning curve of personnel training to use the equipment.

Injections of cidofovir or Foscan-photodynamic therapy (PDT) could also run in tandem with surgical treatment. Dr. Derkay's report of an NIH-funded PDT study at Long Island Jewish Medical Center showed that, in 18 patients, intravenously-administered Foscan followed six days later by PDT led to lessened photosensitivity and a consistent delayed response. Patients showed a trend of worsened condition in the first six months following PDT -- though in laryngeal cases, 6/10 patients were reported to be disease-free at a one-year follow-up examination, and 2/3 of tracheal papilloma cases were deemed to be markedly better.

Of fourteen adults treated with intralesional cidofovir injections in a similar study reported by Dr. Derkay, an average of six monthly injections per patient was required to achieve remission, and a favorable response was observed in all fourteen adults tracked in the study with a reasonably short follow-up period. In a separate presentation, Dr. Pransky offered further benefits of cidofovir treatment given cidofovir's inhibition of HPV DNA polymerase and its long intracellular half-life. He cited the reduced fear of distal spread of papillomas, improved voice quality and emotional well-being, and lessened physician-induced damage. Consequently, there is discussion of a prospective multi-center pediatric RRP study, depending on the logistics of funding and cooperation by Gilead and FDA approval.

Other discussions at the seminar focused on two other perspectives of papilloma management - prevention based on genetic links, and the treatment of already-damaged vocal fold tissue. Ferrel Buchinsky, MD, of Pittsburgh's Allegheny General Hospital emphasized that RRP is not a classic genetic disease - that is, there are few, if any, multiple occurrences in a single family according to traditional pedigree. He introduced stances on a genetic understanding of RRP, confirming that HPV6 and HPV11 are, indeed, causes of RRP - and suggesting that, perhaps, there may be other conditions that weigh heavily in the appearance or absence of the virus in individuals exposed to the virus in the vaginal delivery canal. A promising lead may be the disproportionate frequency of certain forms of HLA proteins in the RRP sample population - notable because, while everyone has these self-recognition mechanism proteins, the rabbit equivalent of human HLA proteins has been observed to be more likely to clear the infection of rabbit papilloma. For the time being, Dr. Buchinsky suggested the exploration of TDT as a method of identifying areas of genes or chromosomes linked to RRP based on gametogenesis patterns. However, for studies to be launched and continued, samples of blood and papilloma from afflicted patients and both parents (if possible) are needed, pending the approval of funding from the NIH.

On the complementary end of the treatment spectrum, Clark Rosen, MD, of the University of Pittsburgh Voice Center actively endorsed methods of post-surgical improvement of voice quality. Outlining the tracheal airflow and presssure-related physiological components of voice projection, he compared the injury to the normally elastic lamina propria and post-surgical swelling and reduced flexibility of vocal cords to " a big piece of gum on a guitar string." Dr. Rosen's recommendation for vocal cord care centered mainly on singing therapy, treating co-morbid conditions affecting the larynx, and avoiding laser treatment in favor of precise phonomicrosurgery and measures of vocal hygiene, as well as processes of vocal fold medialization to bring damaged cords closer together via lipoinjection or thyroplasty. The collagen injections discussed by Dr. Rosen work directly on the shrunken lamina propria, while fat graft vocal fold reconstruction involves elevation of the vocal cords to incise and release scar tissue, which is replaced by the patient's own fat as a barrier against regrowth of scar tissue and as a medium with strong vibratory properties.

"We're not making [patients into] singers," Dr. Rosen reminded the audience, touching on the common aim of all divergent recommendations and opinions presented at the three-hour seminar. "We're giving them a better quality of life."
 
 

RRP TASK FORCE MEETING AGENDA

SUNDAY SEPTEMBER 21, 2003

5:30-6:30 PM

Orlando, Florida

I. Introduction of Members

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II. RRP Registry Update: Beth Unger

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III. Research Initiatives

a. Farrell Buchinsky-Genetic Mapping

b. HSP-E7

c. HPV 6/11 vaccine

d. Cidofovir

e. Maternal-fetal transmission risk-factor study

f. GERD

g. Celebrex

h. Microdebrider

i. RRPF/International RRP ISA surveys

j. International HPV meeting Mexico City, 2/2004

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      IV.             Future of RRP task force

  V.            Future Meetings - ASPO Phoenix, AZ

                                                         May 2-3, 2004

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
 

Patient/family assessed impact of some adjuvant therapies reported.
 

Other therapies, not showm above, that have shown some efficacy include PDT (photodynamic therapy) and Acyclovir.

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

HPV Vaccines

Omega-3 Fatty Acids (Fish Oil)

Cox-2 inhibitors (eg., Celebrex)

Cimetidine (Tagamet)

Some notes regarding the above chart:

The therapies are documented as follows IFN = interferon, I3C/DIM = indole-3-carbinol (I3C) or Diindolylmethane (DIM),Cidofovir , MumpsVax = mumps/MMR vaccine, Retin = retinoicacid or accutane.

Other therapies with anecdotal reports of efficacy, include: Echinacea and Thuja (homeopathic anti-virals), a mixture of vitamins including vitamin C and vitamin A, ShapeRite immune formula, colloidal silver, topical 5-flourouracil (5FU), bleomycin and cobalt. (These treatments are generally unsubstantiated and some may involve significant side effects. The RRPF makes no recommendation for their usage.)

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-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

877-312-5777 or 303-447-3841 - phone; 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.

Estimated dosages; BioResponse recommends that individuals with RRP choose a daily dose which is close to 5-8 mg/kg/day. A typical man weighing 70-85 kg (where kg. = 2.2 lbs.) would take approximately 350 to 600 mg per day. A typical woman weighing 60-70 kg would take from 300 to 500 mg per day.

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 ($3.85 up to 1 lbs.) , or global priority. Call or e-mail for product pricing

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.)

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
 
 

[Note: Kronos Pharmacy now requires prescriptions for 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

* A few anecdotal instances of lowered bone density
 

The pulse dye laser is a laser that has been in use in treating vascular lesions in other parts of the body for many years. Over the past few years, it has been used in the treatment of RRP.

The pulse dye laser works by penetrating the epithelium without damaging it and is selectively absorbed by the microvasculature (blood supply) of the diseased site. Once absorbed by the microvasculature, it results in a disruption of the oxygen and nutritional support to the disease site and impedes the survival of the papilloma. Due to the selective absorption in the microvasculature of the papilloma, the pulse dye laser does not disturb the surrounding tissues, thus minimizing the vocal scarring that can result from other repeated surgical procedures. Due to the selective absorption and minimal damage to the epithelium, the pliability of the vocal folds is maintained. It is the damage to the lamina propria, beneath the epithelium, that causes scarring. It has also been reported that the pulse dye laser does not fully remove the epithelium, thus treatment of the anterior commissure is possible with one surgery rather than a staged approach of two surgeries.

Recently, the pulse dye laser has also been used in an office setting by using local anesthesia, rather than undergoing general anesthesia. This is outlined by Tony Lekas, who is an RRP patient, at www.lekas.org/tony/rrp.html. Tony has provided great detail on his treatment history which includes both surgeries under general anesthesia as well as the pulse dye laser in an office setting.

The above outlined study delineates a number of advantages for the pulse dye laser in the treatment of RRP. It also has some disadvantages, namely expense and lack of general availability in the operating room. In addition, the pulse dye laser isn't as effective on large lesions due to the lack of penetration. The use of this laser is relatively new and we expect additional studies and information will become available in the future.
 
 
 
 
 
 
 
 
 
 

Science & Research Activities
 

A Phase II clinical trial, conducted by Stressgen BioTechnologies, involving children with Recurrent Respiratory Papillomatosis (RRP), using the immunotherapeutic vaccine, HspE7, has been completedAdditional information since earlier results in June indicating that more patients have achieved a doubling in their surgical interval with longer follow-up, is very encouraging. A copy of the full poster presented at the ICAAC is available from the Stressgen website or at:

http://www.rrpf.org/rrpf/therapies/HspE7_ICAAC.pdf.

Below is a copy of a press release from Stressgen based on a poster that was presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
 
 

STRESSGEN PRESENTS RESULTS OF PEDIATRIC PHASE II RRP TRIAL AT ICAAC SUPPORTING PIVOTAL PHASE III TRIAL
 
 

Projected That More Than 50 Surgeries Avoided During Year After Treatment with HspE7

FOR IMMEDIATE RELEASE September 16, 2003

Chicago, Illinois USA - Stressgen Biotechnologies Corporation (TSX:SSB) today presented interim data from its Phase II trial with HspE7 in recurrent respiratory papillomatosis (RRP), a seriously debilitating and sometimes life-threatening condition for children, at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, Illinois. These data will be available on the Company's website at www.stressgen.com.

The primary endpoint of the Phase II trial evaluated the interval between surgeries following treatment with HspE7 compared to the pretreatment surgical interval. The increase in the first post-treatment intersurgical interval is statistically significant (p<0.01); likewise, the increase in the median of all post-treatment intervals is statistically significant (p<0.05). For the overall population, the first post-treatment interval increased 78.6 percent over the pretreatment interval, resulting in fewer surgeries for these patients. Almost half of these children were rated "severe" by a laryngeal scale score or by having papillomas in their lungs (lung involvement is the most serious manifestation of RRP). The annualized surgical rate was calculated, along with the change in the patient's surgical rate after treatment with HspE7. These data indicated that the annual number of surgeries RRP patients would require is reduced by 37% with HspE7 therapy. This reduction in the number of surgeries after treatment is highly statistically significant (p<.0001). It is projected that more than 50 surgeries will have been avoided during the year after treatment with HspE7 among the patients who experienced at least one surgery reduction compared with the pretreatment period.

Additional results from this Phase II trial, including follow-up data on approximately 50 percent of the patients who have completed the 60-week study, will be presented at the Society for Ear, Nose and Throat Advances in Children (SENTAC) meeting in New Orleans on October 30-November 1, 2003.

"We're very excited about the positive effect of HspE7 in treating these seriously ill children," said John R. Neefe, M.D., Senior Vice President of Clinical Development. "Treatment with HspE7 reduced the number of times these children undergo a surgical excision under anesthesia, an emotionally draining ordeal. Remarkably, surgery has not been required in some patients since treatment with HspE7, and in most children with improvement, their improvement is being sustained." Whereas spontaneous doubling of the intersurgical intervals is unexpected in pediatric RRP, 30 percent of these patients achieved a doubling of the first intersurgical interval after therapy. Additional patients, who did not have an immediate improvement in surgical interval, have doubled their interval with continued follow up. To date, 41 percent of patients have achieved doubled intervals after treatment. The expansion of the list of improved patients with the passage of additional months is consistent with data seen in previous HspE7 clinical trials in patients with genital warts and anal dysplasia.

HspE7 was well tolerated in this pediatric population. The most common side effect was mild to moderate reaction at the site of injection.

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

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Revisiting Cox-2 inhibitors for treating RRP

[Ed. Note: Much of the information in the following article was supplied to the RRPF by a knowledgable and reliable source.]

The RRP Foundation Reference Service issue from the summer of 1999 cited a paper by Robinson et al., 1999, that suggested the possible role of COX-2 in papillomas. Their conclusions were, "There is an elevation of COX-2 expression in papilloma tissues. This may represent a causal role of COX-2 in the formation and proliferation of laryngeal papilloma. There may also be a role for selective COX-2 inhibition for the treatment of laryngeal papilloma."

Cox-2 is responsible for the inflammation process (which is the basis for the FDA approval of COX-2 inhibitors, such as Celebrex, for treating arthritis) and triggering a production of vascular endothelial growth factor (VEGF), which is the angiogenic factor that supports the development of new blood vessels which are necessary to grow and feed new polyps and tumors. Cox-2 causes an over expression of Sp 1, which then drives VEGF over expression, which is involved in dysplasia, polyp progression and tumor development in pancreatic, colon, prostate, gastric, sino/nasal, gastric, brain and breast cancer. Cox-2 is usually over expressed in these cancers, by between 10 to13 times. As noted above, it is also similarly over expressed in papilloma tumors of RRP patients.

So in theory it makes sense that a selective Cox-2 inhibitor could work to eliminate most polyps and tumors, including papilloma. Celebrex, Rofecoxib, Vioxx and Bextra are all selective Cox-2 inhibitors. Celebrex appears to be one of the safest COX-2 inhibitor products that is approved. As millions of people across the U.S. are taking Celebrex for arthritis inflammation. Furthermore the MD Anderson clinic is conducting a number of clinical trials using Celebrex to treat/prevent a variety of cancers and ployps. Why not try Celebrex for treating RRP in an off-label clinical trial?

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A proposal by researchers at the North Shore-Long Island Jewish Research Institute to determine why some persons respond to treatment with indole-3-carbinol or diindolylmethane (I3C/DIM) while others appear to be refractory, is still unfunded. The RRPF will keep the community posted regarding any progress. The following is the introductory part of an abstract related to this study which has been accepted for an upcoming meeting of the American Association of Cancer Research:
 

Chandrasekaran, A., Guzowski, D., Gawel, C., Courtney, S., Ruzsicska, B., Chen, D.Z., Shi, Y.E., Carter T., Auborn, K., Goodwin, L.O. North Shore-Long Island Jewish Research Institute, Manhasset, NY.

Breast cancer represents the second leading cause of cancer death in women in the United States (40,600 yearly), with 192,000 new cases in 2001. This disease exacts an enormous toll in health care costs and loss and suffering. Though, progress has been made with early diagnosis and treatment, prevention remains the best defense. In a retrospective study of postmenopausal women in Sweden, the rate of breast cancer was inversely correlated with ingestion of cruciferous vegetables; which contain effective natural prophylactic and antitumor agents, for breast and prostate cancers, such as I3C and major congener diindolymethane (DIM). I3C/DIM: induces many Phase I and II enzymes through the aryl hydrocarbon receptor (AhR); alters estrogen activities; causes growth arrest and induces apoptosis (1-3). Microarray profiling shows that I3C/DIM changes the expression of more than 100 genes in epithelial cells (4). Populations that consume copious cruciferous vegetables include a cohort that atypically develops cancers. I3C/DIM treatment of patients with laryngeal papillomas or precancerous lesions of the cervix, reveals a subset (1/3) of persons refractory to its benefits. Many cancers have polymorphisms in one or more of the genes influenced by I3C. We hypothesize functional polymorphisms in one or more genes regulated directly or indirectly by I3C governs an individual's ability to respond or not to treatment.

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[The following information involves excerpts and summarization of an abstract submitted by Jonathan P. Lindman, MD of U.A.B. It describes the approach and results from a study which has been funded by the RRP Foundation.]

Use of the PedsQL[tm] to Assess Health-Related Quality of Life in Children with Recurrent Respiratory Papillomatosis
 
 

The objective of this study was to use the Pediatric Quality of Life Inventory (PedsQL), a 23-question modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents, to measure HRQOL in children with recurrent respiratory papillomatosis (RRP) and their parents Their HRQOL is compared to that reported for healthy children and children with other chronic medical conditions.

The PedsQL 4.0 Generic Core focuses on 4 main catagories: Physical, Emotional, Social, and School. For ages 2-4 it is only parent-proxy reporting. Parents also report on HRQOL in children ages 5 to 18, however, there is child self-reporting for ages 5 to 7 (with age-adjusted questions and rating scales) and 8 to 18. The questionnaires were administered in person or by telephone to 27 children with RRP (The mean annual number of surgeries for the RRP patients was about 3.5 and the mean total number of surgeries over the course of the disease to date was 20.67.) and (or, for children 2 to 4) one parent. Results were compared to validated norms for healthy children and scores for children with other chronic medical conditions.

Children with RRP report a lower quality of life than do those who are healthy and a similar quality of life to those who have other chronic medical problems (although their parents perceive a lower quality of life). Parents of children with RRP also perceive a lower quality of life for children affected by this disease when compared with healthy children. The PedsQL may be utilized to evaluate HRQOL outcomes of clinical or experimental treatments for children with RRP.
 
 

It is with much sadness that we write about the death of RRP patient, Alexa Rae Phillipakis-Patten. She passed away a month before her fourth birthday, on October 10, 2002. In her three year battle with RRP, Alexa underwent 17 surgeries. She had been requiring surgeries about every 2 months, but several weeks before she died, her grandmother and father (with whom she lived) noticed that her breathing had become more strained. They contacted their doctor's office to try to move up the date of Alexa's next surgery, but the office convinced them to keep the appointment. Alexa's grandmother and father requested that she be put on a regular schedule for surgery every three weeks but the doctor's office refused, saying that the anesthetic would be to hard on Alexa. Tragically, Alexa never made it to her scheduled appointment.

It is quite upsetting that the doctor's office did not respect the observations of those closest to Alexa. Parents and guardians, who are almost constantly with their children, clearly have the best perspective to assess early signs of airway deterioration. Many RRP practitioners understand this and will be responsive to their observations and judgement. It is Alexa's legacy and our sincere hope that no other RRP child will ever suffer such a tragic fate.

Alexa is survived by her father Constantine, her mother Malina, her grandmother Karen (yia yia), her aunt and godmother Anastasia, plus many other family and friends who loved her so dearly and miss her so very much.
 
 

The following addition is from Alexa's grandmother:

"Alexa's family mourn her everyday and wish with all of their heart's that they would have gone over the doctor's staff and rushed her to the hospital. It is so much better to be safe than it is to be as sorry as we are. Our love to you all who deal with RRP, be strong."
Karen Phillipakis
 
 

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
 
 

Bill Widmayer

744 Hickory Ridge Rd. SW

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

e-mail: widmayer@mindspring.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: corschneike@t-online.de
 
 
 
 

California
 
 

Cheryl Downey
2520 Pearl Street

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

Georgia
 
 

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
 
 

Utah

Geni Mesi

5824 South 2050 West

Roy, Utah 84067 (801) 377-4937
e-mail: mesifam@hotmail.com

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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