Vol.9 No. 1 An RRP Foundation Publication 2000 Summer
P.O Box 6643, Lawrenceville, NJ 08648-0643

______________________________________________________________________________________________________________________

Contents

Opening Comments - p1

Special Acknowledgements - p1

RRPF Organization Information - p2

RRPF Publication and Subscription Policy - p2

RRP Remission - p2-3

RRP Network News - p3
Proposed RRP Focus Session at AAO Meeting - p3
RRP Web/Internet News - p3
Trach Talk - p3-4

RRPF Listerve Highlights - p4-5

RRP Patient Statistics - p5-6

RRP National Issues - p6
Creating Greater Awareness of RRP - p 6
RRP Registry Update- p6

Adjunct Therapies and Protocol Update - p 6-10
I3C/DIM - p 7-9
Phytosorb-DIM - p 7-8
I3C and Bone Density - p 8-9
Cidofovir - p 9-10
Photo-Dynamic Therapy (PDT) - p 10
Patient Profile - p 10

Memorial - p 10

From the Editor

This issue of the RRP Newsletter is dedicated to RRP patient, Dorothy McDonald, who passed away recently and was a member of our support group. A short memorial can be found on page 10.

Some of you may have noticed that this edition of the RRP Newsletter has fallen a bit later in the year than normal. Beginning with this issue, we are changing the newsletter circulation dates from the former Fall/Spring cycle to a Winter/Summer cycle. The new cycle of Winter/Summer fits the newsletter contributors schedule better than the current cycle. While the distribution date of the newsletter is later than normal, we would like to take this opportunity to solicit volunteers who could help support the RRP Foundation. We have grown considerably as an organization over the past eight years and could use additional support in a number of areas. Specifically, database management, data gathering, fund raising, assisting with articles and investigative research. We are also looking for assistance with some of the Foundation day-to-day operations. If you are interested in assisting in some capacity, please contact Bill Stern.

Chris J. Neuberger

(405) 749-8499

Email: Cneuberger@horizonfleet.com

P.S. Thanks to Lindsay and her friends Brielle, Megan, Allison, Sadie and Katie who helped stamp, address and stuff these newsletter mailing envelopes.

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. A few special acknowledgments are listed below. 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.

Special Acknowledgments:

We are most grateful to the family and friends of Dorothy McDonald who generously donated to the RRP Foundation in her memory.

We also thank the Medtronic Foundation who made a generous donation to the RRPF via their Time-n-Talent Fund.
 
 

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 2002, C.C. Wu Building
308 Hennessey Rd.
Wanchai
Hong Kong
henry.woo@medtronic.com

Diane Burke, RN
Director
Department of Otolaryngology
The Univ. of Iowa Hospitals and Clinics
E230 GH, 200 Hawkins Drive
Iowa City, IA 52242
(319) 356-1765
diane-burke@uiowa.edu

Susan Woo
Director
101 Repulse Bay Road
Apt. A3/1st floor
Hong Kong
852-2812-7379
writeus@attmysite.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 Medical Care Center
 
 

RRP Newsletter Editor

Chris Neuberger

Other RRP Newsletter Contibutors

Wayne Barringer

Toni Barringer

Dale Barringer

Marlene Stern

Bill Stern

RRP Reference Service Editor

David Wunrow

RRPF Fundraising Coordinator

Ed Weiner
(703) 691-1922
serviceimpact@msn.com

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

The RRPF produces two publications semi-annually, 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 Suggested Minimum Annual Donations

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

RRP Remission News

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

It's been three years since nine-year-old Alison from Virginia has needed surgery. She has been checked once a year and remains clear of papilloma. Her parents attribute her remission to I3C.

Mike from Georgia, who is 47, has not required surgery for about 2 years. He credits I3C for this remission from RRP.
 
 

Others still in remission (from 2.5 to 15 years) include: Nine year old Ariel from California; Thirteen year old Andy from California; Christie from Florida - eleven years old; 26 year old Julie from Florida, Steph from Florida, age 27; Jeff from Illinois, age 53; William from Illinois, at age 76; Jessica from Kansas who is now 9 1/2; Twelve year old Anthony from Kentucky; Cara from Michigan at age 18; Leah from New Hampshire, age 20; 10 year old Lindsay from New Jersey; Julie from New York, who is 22; Joe from Ohio at age 33; Ralph from Pennsylvania at age 73; and Smokey from Virginia, age 28. Of this group still in remission about 2/3 have attributed their remission to some form of adjunct therapy, the most common being I3C and/or DIM. Other therapies included interferon, 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 510 respiratory papilloma families. Patients range in age from about 1 to 86 years. Domestically, patients are located in 47 states plus the District of Columbia. Outside the U.S. there are currently 27 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 box located near the top of the front side. 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 fill out the form enclosed. If you have previously filled out a questionnaire, you need only identify yourself, mark UPDATE along the top front of the form and answer only those questions where you have new or updated information to provide. Please return the surveys to Marlene and Bill Stern. Alternatively, you may submit questionnaires via our website (http://www.rrpf.org) by filling out the online "patient survey".

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

In conjunction with this years annual meeting of the American Academy of Otolaryngology (AAO), we are proposing to hold a national RRP support group meeting. The RRP Foundation will be attending and participating in AAO annual meeting to be held in Washington D.C. from 24-27 September 2000. We are proposing to sponsor a special meeting to be held on Saturday 23 September 2000. All RRP patients/families are invited to attend. We are also encouraging interested doctors and nurses to join us as well. We hope to have at least one and perhaps two guest speakers. Since we will need to make arrangements for this meeting well in advance, we are asking those of you who plan to attend to let us know no later that 15 July 2000 so that we can get a good estimate of the magnitude of the meeting in time to make the appropriate arrangements. We are also asking for volunteers to help out with our exhibit booth, especially for Wednesday September 27.

Please RSVP to Bill or Marlene Stern (see contact information on page 2). Looking forward to seeing you there!

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

The use of the internet has provided a valuable mechanism of information exchange for the RRPF. Our website (http://www.rrpf.org) contains a wealth of information relevant to patients, families, doctors, nurses and researchers. 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 now 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 Listerve that currently has about 156 subscribers with nearly 800 postings. The RRP Listerve, maintained by Dr. Ed Beck, is a secure web based environment for communicating RRP based information. If you haven't joined yet, please feel free to do so by sending a blank email to:
rrpf-subscribe@egroups.com. As of March 2000, the RRPF has been using the RRP listerve and the RRPF Discussion Forum instead of the previously used email distribution list to send communications to the RRP community. Please be sure to sign up for the listerve if you haven't already done so. Over the past few months we have seen some very interesting information exchanged via the listerve. We have devoted an article in this newsletter to summarizing some of the information from this forum.

We also maintain links with other sites relating to RRP including the RRP Website and the website of the ALPF..

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

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

107 Salem Drive, Montgomery, AL 36109_2741, U.S.A.

Email : trachlady1@yahoo.com

The following has been excerpted from the "Trach Talk" section of the RRPF website (http://www.rrpf.org/rrpf/Trach_Talk.htm):
 
 

This is an expensive machine (cost me $1,100.00) but it can help us if we can afford it. It is called an Oxygen Saturation Monitor and can be used for adult and children patients. The baby patients would probably need an adult nearby to help with the sleeping habits. What an alert(non-comatose) trach patient can expect from this machine is this:

The ability to align your tracheostomy tube with your airway especially when sleeping. This means increased oxygen supply to your heart and brain reduce the number off cells that die for lack of oxygen. With better alignment of the trach, comes decreased number and size of red bloody rings from the trach through the night.

The unit monitors heart beat to warn of low heart rate. Coughing or getting up and moving will usually take care of this problem. Your doctor will advise you further. Help comes when we sleep, since changing position can partially close our airway and effect our heart rate and oxygen blood supply. The alarms from the machine can allow us to adjust our position without having to be fully awake. I find my quality of sleep and awake time is improved. When using the unit my fingernails are even almost cherry red to show good oxygenation.

Oxygen Saturation Monitors are a prescription item so talk to your doctor to see if it is appropriate for you. I have not found this unit to be covered by insurance but your insurance may cover it.
 
 

RRPF ListServe Highlights

There are so many questions about RRP, it's often overwhelming to try and find answers. One of the best places, however, is just a few keystrokes away. The RRPF. email listserve has been extremely popular. It's easy to use - just sign up and open up your email program. If you have a question, odds are someone on the list will have an opinion or has researched an answer. There are now more than 156 subscribers to the list - there's strength in numbers.

Following is a condensed highlight reel of issues that have been discussed on the RRPF email list. We have paraphrased questions and answers. If you'd like to sign up to join the list, follow the instructions in the Web/Internet News section.
[Ed. Note: Many of the listeserve messages are from individuals who believe their posts to be factual, however, the RRPF cannot guarantee the accuracy of all posts made to the listserve, especially those that represent an individual opinion.]

Some believe that 5% of Americans may have HPV in their respiratory tracts, but only about .005% of Americans have RRP. So, what other factors (immunological? genetic? environmental? etc?) are important in allowing the virus to progress to RRP rather than just stay dormant.

(In 1993 Bill Stern) polled 8 RRP experts who collectively had been involved in more than 1000 RRP cases: "Is there evidence that RRP is contagious to family or in social settings?". The conclusion: there are no documented cases of RRP occurring among siblings, marital partners or family members. Since these are people who would constantly be exposed to secretions from RRP patients, I think it is safe to conclude that RRP is not contagious in social and even intimate situations.

There are two types of endoscopes: a rigid one that looks like a wand, which is about the diameter of a pencil and goes in your mouth. Some patients are extremely gaggy and can't tolerate anything touching the back of the throat - topical anesthesia can be used to improve comfort. The second type is a flexible nasoendoscope. Which goes in through the nose and has the diameter of a thick spaghetti noodle. Usually a spritz of decongestant is used first followed by topical anesthetic. Physicians can see the vocal cords clearly with both.

My son was scoped once - never again. I taught him that when the doctor holds his tongue he must keep breathing and he stopped panicking. Now the doctor can get a good look with just a mirror.

I have a very nasty gag reflex so I threw up every time I was scoped until I went to Dr. Plant in Norfolk, VA. He has a great trick, which worked every time. First I was sprayed, then scoped through my nose. His wonderful nurse stood next to me and, just when I knew I was going to gag, she put her hand firmly on my shoulder. My mind immediately focuses on the hand since it is unexpected. This works every time

The RRP Foundation has received chemical assay information regarding Indolplex, produced by BioResponse. I am pleased to say that the analysis shows qualitative verification of the product contents as specified by BioResponse, i.e., primarily DIM combined with a lesser amount of Vitamin E. (I do not have quantitative figures available at this time.) Our thanks to the RRPF European coordinator, Dr. Jan Schneider-Eicke, who made all the arrangements for this analysis with a highly regarded pharmaceutical lab in Italy.

My son's webbing would keep coming back until they used scissors instead of lasering it

My son's doctor made a flap from the scar tissue to cover the vocal cord after lasering. He said this is the first time he's tried it but read about it in journals.

My various surgeons have all had the same approach - only laser on one side of the "V" in a surgery. The web gets created, as I understand, when both sides are lasered and they have a chance to heal together.

Jackie told a hospital social worker (who interviewed her to see why she was so well adjusted to the many hospital visits so they could help other children) the reasons why she did not mind going to the hospital. The were:

1. The surgery helps me to breathe better

2. Everybody loves me, the DR's, Nurses, CFL, and my Mom, Dad, Grandma and Grandpa.

3. I get enough drugs for pain.
 
 

4. I get a present from my grandma every time I go to the hospital.

5. I can eat whatever I want, even popsicles all day.

All the hospital staff knows him. There is a recovery room nurse who signs up for Marty every time she works. The hospital has a volunteer who helps with the children (she does a great job), and Marty gets whatever he wants. They have a gameboy in the playroom. After we leave the hospital we go to Burger King and then usually stop at a store so he can pick out a toy. I also think it really helps that the same people are there each time.

Before my daughter started on Cidofovir I did some research to find out as much about the drug as I could. I did speak to a representative at the FDA. He explained that although it is in research or protocol stages for RRP, any doctor can get their hands on it because it has been approved for use for other diseases. They get it for an "off-label" use.

My daughter Kimmy has been on Cidofovir since the beginning of the summer. Her severe RRP has significantly slowed down and in September we started using Cidofovir.

Cidofovir, as it was explained to me, is an anti-viral medicine. That is why they use it in aids patients. It does help their immune system fight off illness due to aids, but does not kill the aids virus. However, the patients with RRP that my daughter's doctor has been treating, have either gone into remission, or improved very dramatically. It has been 3 months since the last time they removed papillomas from her vocal chords, and gave her the three injections. She goes for her fourth injection on Tues, and she still has a very strong voice where she wouldn't have had one at all by now. My husband and I are very impressed with the results and are excited about what this drug can mean for our daughter!

Yes, Cidofovir can cause irreparable kidney damage. The secret to that not happening is proper hydration and proper dose. I have read that Cidofovir actually attacks the virus. It was actually discovered for, and is, used to treat aids. Check with your Doctor or get an infectious disease expert to work with your case.

The IV Cidofovir is the same drug as is given in Intralesional Injections, but it is given in a much higher dose. It should only be given in the most severe cases. Cidofovir can cause irreversible kidney failure and the child must be monitored closely, kept properly hydrated before and after the injections.

Jackie goes into the Cancer center for outpatient care, is hydrated with fluids, then given the Cidofovir, then hydrated again. This drug is very dangerous to the kidneys so we are working with an Infectious Disease Specialist who worked up this regime for her. It started out as a 6-hour process and now it is about 3 1/2-4 hour process. She has had about eight treatments given to her every other week. No side effects (so far) other then an occasional headache and she seems to be a little hyper after the treatment.

[Ed. Note: Cidofovir is approved for use in HIV patients with CMV retinitis. Snoeck et. al., 1998, indicated that the problem of nephrotoxicity is almost exclusively related to the intravenous use of the drug. Using Cidofovir intralesionally results in almost no absorbtion into the bloodstream, therefore it is not expected to create any nephrological problems.]

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 418 to 474 for tables 1-3.

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

	Females	Males
All Ages	210	264

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

Age Groups	Females	Males	Total
Under 10	68	54	122
10-20	40	44	84
20-30	23	20	43
30-40	26	31	57
40-50	16	33	49
Over 50	16	47	63

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

Age Groups	Females	Males	Total
Under 10	144	129	273
10-20	11	7	18
20-30	22	29	51
30-40	7	35	42
40-50	8	25	33
Over 50	4	14	18

 

Table 4. Distribution of respiratory papilloma sites of involvement based on responses from 272 patients.
 

respiratory site	no. of patients
above cords	135
at cords	272
below cords	107
tracheal	47
bronchial	24
lung	17

 

 Table 5. Birth Statistics from Patient Support Network*:

Cesarean birth in 19 cases - 354 responses

juvenile onset: 11 of 220 responses

adult onset: 8 of 134 responses

Patient is first born in 180 cases - 339 responses

juvenile onset: 136 of 205 responses

adult onset: 44 of 134 responses

Patient was adopted in 47 cases - 362 responses

juvenile onset: 43 of 224 responses

adult onset: 4 of 138 responses
 

Mother's ages -
171 responses (juvenile onset only)

Under 20 = 45
20 -> 25 = 65
> 25 = 61

106 responses (adult onset only)

Under 20 = 8
20 -> 25 = 28
> 25 = 70

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	59/59	65/81
No	86/49	69/34

 

RRP National Issues

A number of proposed scientific and clinical studies involving promising therapies for the treatment of RRP are in need of funding. Government agencies are a very significant source of support for these RRP research efforts. In this regard we continue to urge you to contact your congressional representatives and senators to make them aware of RRP and mobilize their support. For names and addresses of specific key governmental officials see the RRP Newsletter Spring 97 issue.

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

I'm Wayne Barringer, a 31-year-old, lifelong RRP battler. I've found great comfort over the past few months in discovering this organization and the tremendous people who keep hope and support alive.

In talking recently with Bill Stern, I have offered to help the foundation build some awareness in the press and news media. If we can persuade members of the press to write and speak about RRP, I believe we can achieve this goal: Raising funds for the foundation that would support research toward treatments and cures for RRP.

I work with the media every day - in the public relations profession - and I'd like to offer my expertise in this area. I believe that with a little proactive educating on our part, there are many reporters who'd be very interested in some of our stories.

Bill and I will be working on a complete plan to help promote RRP awareness in different cities. For now, we'd like to ask that anyone interested in furthering this effort to please contact me directly at waynebarringer@earthlink.net or by phone (425) 827-1274.

By helping, we'll ask folks to do the following:

1. Talk with me about your or your child's RRP situation

2. Discuss whether you'd be willing to share your story with a local press person in your town or city

3. Share any other ideas for positive PR that we can pursue.

I've seen the power of the coming together of individuals - that community spirit on this list is extraordinary. Let's harness that and try to drive something even more wonderful - more research and rapid progress toward proven treatments and even eradication of RRP.

Thanks, and please contact me with questions, comments and your stories.

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

Site #	child per site	males	Fem.	mean age per site (yrs)	mean age at diag. (yrs)	mean years with RRP	mean procedures per child
101	42	25	17	8.56	3.63	3.87	13.83
601 .2	13	5	8	10.16	3.86	4.68	25.23
602	29	13	16	9.29	3.48	3.66	20.55
1101	24	12	12	9.83	3.96	3.42	21.63
1201	24	15	9	9.40	5.87	2.06	6.13
1301	29	12	17	7.93	3.88	3.04	14.48
1901	24	11	13	9.86	3.11	5.88	27.04
2401	16	7	9	9.84	5.15	3.32	16.38
2501	22	7	15	9.85	3.80	4.97	25.68
2701	3	1	2	8.52	4.08	3.51	18.00
2901	23	16	7	10.27	3.29	6.05	25.74
3602	25	12	13	11.40	4.13	6.27	15.24
3701	25	9	16	8.10	3.33	4.16	15.08
3901	29	14	15	10.36	3.81	5.51	35.38
3902	21	9	12	9.79	3.84	4.63	17.00
4201	27	14	13	12.28	4.08	6.61	28.81
4701	10	3	7	7.20	2.62	3.98	15.80
4702	27	13	14	11.11	4.42	5.53	28.30
4801	46	24	22	10.58	4.45	4.34	15.72
4901	15	9	6	6.42	2.58	2.48	10.40
5101	24	11	13	10.75	6.19	2.37	8.00
5301	37	21	16	10.52	3.25	6.39	24.00
Total	535	263	272
Overall Mean				9.82 N=535	3.98 N=489	4.52 N=492	19.65 N=535

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.
 
 

252 RRP patients/families have reported using at least 1 adjunct therapy. The most reported therapy was I3C/DIM with 169 users and next was interferon (IFN) with 82 users responding. The patient/parent assessed impact of some adjuvant therapies is summarized in the table that follows. In this table the sample sizes include only the subset of adjunct therapy users who indicated some response to a treatment, either some improvement (Improve) or no impact (None). If some improvement is noted, it is further broken down into either a complete response (Comp, i.e., no new growths seen for at least two typical surgical intervals) or a partial response (Partial).

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.
 
 

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

Therapy	Users	None	Improve	Comp	Partial
I3C/DIM	108	50	58	22	36
IFN	52	21	31	4	27
Acyc	31	20	11	4	7
PDT*	17	11	6	1	5
Ribvrn	3	1	2	0	2
Retin	16	9	7	0	7
Mumps	12	5	7	1	6
Cidofovir	7	1	6	1	5

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 (*most respondents to date were treated with the older agent, photofrin, not the new agent mTHPC - see page 10 for more on PDT using this improved agent) , 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, such as the RRP Newsletter Spring 97 issue 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 for DIM, as well as Bradlow et al., 1996 J. of Endocrinology 150, S259-S265; Newfield et al., 1993, Anticancer Research 13, 337-342.
 
 

BioResponse Nutrients is pleased to announce to members of the RRP community using Indolplex that this successful product is being renamed and released as Phytosorb-DIM. DIM is short for diindolylmethane which is a phytonutrient found in cruciferous vegetables of benefit as a dietary supplement for RRP.

The patented formulation of DIM, to be sold as Phytosorb-DIM, is unchanged from that found in Indolplex. However, after two years of monitoring the use of this supplement by individuals with RRP, reports indicate more success at a higher dose of 5-8 mg/kg/day of the formulation. This news is important since many individuals, especially older children and adults, have been taking the DIM formulation at a dose closer to 4 mg/kg/day.

Improved Formulations and New Suggested Dose for Phytosorb-DIM

BioResponse has reformulated its "Sprinkles" which are now available with improved chocolate flavor as "Chocolate Sprinkles" and in a new "Orange Sprinkles" flavor. These new formulations require lesser amounts of the powder to deliver the increased suggested dose according to the following guidelines:

Weight in Pounds (lbs)

(2.2 lbs = 1 kg) 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 100lbs 1/2 tsp, 100 to 150 lbs 3/4 tsp

Use of the BioResponse DIM formulation at the higher dose of 5-8 mg/kg/day has been free of any side effects and associated with healthy growth rates in children. Achieving this dose range in adults will often require 3 or 4 capsules per day using 150 mg capsules or combining 150 mg with 75 mg capsules.

Phytosorb-DIM is available in both 150 mg and 75 mg capsules which are identical to those previously sold as Indolplex. The old Indolplex 150 mg capsules (60 per bottle) are now called Phytosorb-DIM 150 and the previous Indolplex 75 mg capsules (90 per bottle) are now called Phytosorb-DIM 75.

Ongoing research concerning natural phytochemicals like DIM provides evidence that these substances may be acting directly in addition to indirect effects through the promotion of healthy estrogen metabolism. Both metabolites of estrogen and metabolites of DIM may be acting together to increase rates of "apoptosis" or programmed cell death which is the body's natural mechanism to eliminate cell damaged by viruses like the human papilloma virus (HPV).

BioResponse will be initiating a new survey offering a month's free supply of Phytosorb-DIM to those individuals using Phytosorb-DIM at a dose of 7-8 mg/kg/day for a period of 6 months.

We again thank the RRP foundation for the opportunity to communicate this exciting news about further progress with Phytosorb-DIM.

We encourage inquiries and would be happy to provide further information to anyone interested in Phytosorb-DIM. Telephone: 303-447-3841 (Elizabeth), Fax: 303-938-8003, or e-mail: etzeligs@sni.net.
 

Phytosorb-DIMTM products containing DIM are available from:

BioResponse
L.L.C. at P.O. Box 288
Boulder, CO 80306
Email at zeligsmd@sni.net
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.

* Now 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.)

Estimated dosages; BioResponse now 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.

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.

(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. Indolplex can be taken by individuals who use antacids or H2 blockers like Zantac.

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
http://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.

Medical Center Compounding Pharmacy
3675 S. Rainbow Blvd, #103
Las Vegas NV 89103
e-mail: mccp@mccpharmacy.com
Tel: 1-800-723-7455
Local: 702-873-8455
Fax: 702-873-6845
http://www.mccpharmacy.com

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

For more detailed information ask to speak with Richard Fura.

Medical Center Compounding 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
* Bone density loss ???
...............................................................................

Indole-3-carbinol (I3C) modulates estrogen metabolism. This alteration in metabolism does not favor the development of papillomas. Hence, I3C and a condensation product formed in the stomach diindolymethane (DIM) are attractive compounds for prevention and treatment of RRP. The compounds originate from cruciferous vegetables (cabbage, brussel sprouts, etc.), compounds that should be relatively safe since many populations eat large quantities of these vegetables. The possibility exists that I3C or DIM could result in some of the adverse effects associated with less estrogen such as osteoporosis. Indeed, a child taking I3C was reported to have osteoporosis (previous issue of RRP newsletter).

The effects of I3C on bones were evaluated by Drs. Karen Auborn at Long Island Jewish Medical Center and Gloria Gronowicz at the University of Connecticut Health in a joint study. Mice were feed a normal diet or a diet supplemented with 2000 ppm I3C for 5, 7 or 13 months. Both males and females were included in study. Bones (calvaia and long bones) were harvested and analyzed by histomorphometry in a blinded study. The results are that virtually no differences were found between any groups in any of the 10 parameters examined. The conclusion is that I3C had no effect on bones as determined by this study.

The RRP Foundation provided support for this study.

[Ed. Note: A second anecdotal case of bone density loss has been reported in an RRP patient. Despite the encouraging results in the mouse study, it still seems reasonable for RRP patients to have a simple bone density scan (DEXA). Additionally, those patients planning to use I3C/DIM should have the scan before and after I3C/DIM therapy.]

Cidofovir is an anti-viral drug that is being used experimentally to treat RRP. Background information on Cidofovir may be found in Snoeck et al., 1998 (J. of Med. Virology 5:219-225) , Pransky et al., (Arch. Otol., 1999) and in RRP Newsletter issues Spring 98, Spring 99, and Fall 99 . Results from preliminary studies and anecdotal reports are encouraging.
 
 

This is a multicenter, placebo-controlled, double blind, FDA approved study. It involves injecting into the lesion base immediately after the lesion is biopsied and ablated with the CO2 laser.

We perform the same basic surgical treatment as we would without the drug and then inject either saline or cidofovir. Initially, only the pharmacist knows what we inject but then there is a safety committee that is made aware of the code and in the event that anyone has an adverse reaction to the drug, or has life-threatening recurrences in the placebo group, we have the option to withhold or add the drug. There is no formal cross-over in the design because the study will only run for one year and then we should have sufficiently valid data to determine if it is effective. At that point any patient could be treated with the drug if they choose. The trachea could be injected if within the reach of the Xomed oro-tracheal/laryngeal injector device-- essentially the upper 2-3 cm only.

The other participating University members of the National Center for Voice and Speech, in addition to Wisconsin, are Univ. of Utah and Univ. of Iowa.
 

At George Washington University, a study is being conducted by Steven Bielamowicz, M.D., in which cidofovir is being used exclusively to manage RRP in adults (age 18 or over). The protocol calls for intra-lesional injections of cidofovir every four weeks without any removal of the lesions. Preliminary results thus far are encouraging, with approximately 15 adults enrolled in the study. According to Dr. Bielamowicz, there is complete resolution of the papilloma in many patients, after about 5 injection sessions.

For more information contact Dr. Steven Bielamowicz at (202) 994-9918.

At a recent meeting of the RRP Task Force, Seth Pransky, MD, from San Diego Children's Hospital has proposed a new open study involving intra-lesional injection of cidofovir to treat RRP. He is proposing that it involve from 5-7 medical centers and enroll at least 30 RRP patients. The patients should have a history of at least 4 surgeries per year. The detailed protocol is not yet available, but he has suggested that the RRP patients be followed for 3 years as part of this study. Dr. Pransky also reported that he has now followed 10 RRP patients from 1 to 3 years who he had treated with cidofovir. His general assessment is that there has been dramatic improvement, but he stops short of calling cidofovir curative. He has not seen any significant side-effects.

Articles about cidofovir are being published by the RRPF as an informational service to the RRP community and should not be interpreted as an unqualified endorsement. A decision to enroll in a cidofovir study or use it as an adjunct treatment, should involve careful consideration of each individual case by each RRP patient or family in consultation with their doctor.

Furthermore, some otolaryngologists treating RRP patients, have expressed concern about cidofovir being used in "inappropriate" situations. One doctor who is currently treating some of his patients with cidofovir, Clark Rosen, MD (Univ. of Pittsburgh), feels there are some RRP cases where the use of cidofovir is hard to justify, such as children recently diagnosed with RRP having little or no surgical and adjunct trreatment history (see his comments below) . Although there is some follow-up for as long as 3 years on a few cidofovir treatment cases, side-effects from long-term treatment with cidofovir are yet to be established. A similar cautious approach in applying this new therapy was expressed, in a recent post to the RRPF discussion forum by Thomas Nicolai, MD (a specialist in pediatric internal medicine and airway disorders) , "I m cautious with any new therapy in children, because side effects may show up only years later, and we usually prefer a drug to be well explored in adult medicine before we start using it in children. However, with a disease such as rrp one is pressed to use new methods rather sooner than later, given the severe burden it represents for patients and parents."

Although it is very tempting to opt for the "latest and greatest" new therapy, with regard to cidofovir, we suggest carefully considering the "risk-reward" as it applies to each individual case of RRP.
 

It is important to remember that RRP has a rich history of "cures" that have either failed or worse failed and injured the patient. There is a quote in an old medical journal from one of the most famous pediatric otolaryngologists that states: "Ultrasound treatment for RRP clearly represents a breakthrough in treatment of this disease." Ultrasound has ended up in the same category as celendine, magnesium, cautery, etc, failed without negative consequences. However, we should remember the significant number of RRP patients that in the not too distant past were irradiated for their disease and now have died because of malignant transformation which probably would have never happened if they hadn't been treated with radiation.

I am an advocate of research for new treatments for RRP and specifically I have had encouraging results with cidofovir, however, it concerns me when RRP patients/parents forget that this is an experimental medication that should only be used on patients with proven severe disease.

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

The Department of Otolaryngology at Long Island Jewish Medical Center is continuing its study of photodynamic therapy for RRP. To date, 14 patients have been treated with the new photosensitizer, Foscan. This drug washes out of skin much more rapidly than Photofrin did, so that patients are not light sensitive for so long. Seven patients have been followed for more than one year after treatment. Five of the seven were free of laryngeal papillomas at one year, and the remission has continued for up to 18 months after treatment for those followed that long. The other two patients showed clear improvement. Two patients also had tracheal papillomas. Tracheal papilloma recurrence has slowed, but continued to occur. We are actively recruiting patients for the study, funded by a grant from the National Institutes of Health. Anyone interested in more information should contact Dr. Allan Abramson at 718-470-7555, or Virginia Mullooly RN, the nurse-coordinator, at 718-470-7011.

Bettie M. Steinberg, PhD
Chief, ENT Research
Long Island Jewish Medical Center
270-05 76th Ave
New Hyde Park, NY 11040
Tel: 718-470-7553
Fax: 718-347-2320

Patient Profile

The following case history is written by Teresa Tulcan and represents her experience with RRP and pregnancy / hormones. Teresa's situation does not appear to be typical.

In early 1992 I began losing range in my singing voice and having slight hoarseness. I feel I made my voice vulnerable to the disease because I had been instructing aerobic classes for seven years (which requires incredible voice use). I was also the singer in a band; therefore I was truly abusing my voice. Of course those activities stopped and I have been careful in protecting my voice since.

In March 1992 I started seeing a doctor for symptoms and my first surgery was done in May 1992, in which the biopsy revealed RRP on the vocal cords. After that point, I had surgeries about every five months. Although I would get out of breath and had difficulty talking at a fast pace or for example while going up stairs, my airway was not significantly affected. The level of my voice would decrease between treatments and when I was extremely hoarse, some words were difficult to pronounce and my decibel level was very low. Those factors would determine my need for surgery.

My last surgery occurred August 1993. My voice quality is still hoarse, but at an acceptable level. My range for singing is limited and I still get breathless-but I am able to function. I personally am very positive that my remission has something to do with hormones. I do not know which hormones or why, but perhaps this personal history will provide some insight.

In December 1993 my voice was becoming very hoarse , but I became pregnant in January 1994 and wanted to postpone surgery as long as possible. By my fourth month (May 1994), I could hardly speak, but for some reason, at around six months into the pregnancy (July 1994), my voice started clearing up and by the end of the pregnancy it was acceptable (never has been normal-but acceptable). I breastfed my child for three months and upon termination of breastfeeding, my voice began to deteriorate slightly. I incidentally went on the birth control pill "Overette 28" in January 1995 and my voice again cleared up. I did not like being on the birth control pill (and still would prefer not). On two different occasions, I went off the first time for four weeks and the second time for two months. I felt my voice quality deteriorated in each case and my husband would agree. So I was resigned to stay on the pill, being that RRP was a much worse option. In January 1997, my husband and I decided we wanted another baby, so after discussion (RRP being a deciding factor) I went off the pill in March 1997 and became pregnant in May 1997 at which time my voice deteriorated. I would hear the familiar concern of people who telephoned asking if I was sick or crying (the same response I would get with active RRP). However, again about my fifth month of pregnancy in October 1997, my voice cleared up to an acceptable degree and to this day has remained clear. I am sure that some hormone within my pregnancy and birth control has brought me into remission. I would love to hear your thoughts and if any studies have occurred.

Dorothy was diagnosed with RRP at the age of 50. Despite enduring over 50 surgeries, battling tracheal cancer and a spread of the RRP to the lungs, Dorothy showed a remarkable zest for life - which is so eloquently expressed by her good friend Susan Spock as she remembers Dorothy: "Dorothy was so determined to live each moment and to learn as much as she could about her disease and face it full on. What an extraordinary woman. The more we talked and communicated, I realized just how lucky I was to have met, and known Dorothy. I think she had a lesson to share with us all. Live life, be proud of your accomplishments and don't take one thing for granted. Take a moment in time and see the sun shine through the trees."

Dorothy, who was 57 when she passed away in March of this year, will be no doubt be missed so very much by many us whose lives she touched. She is survived by her husband Jim, and daughters Sue and Shelly.