| Diabetic Ulcer
II. / Ulcera Diabetica II.
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****** DATA-MEDICOS *********
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ULCERA DIABETICA (II) / DIABETIC ULCER (II)
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***** DERMAGIC-EXPRESS No 16 *********
****** 12 NOVIEMBRE 1.998 *******
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1.) EDITORIAL
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Hola Amigos, Dermagic de nuevo con ustedes. Han salido al mercado varios productos nuevos para el tratamiento de la ulcera diabetica, el REGRANEX, CYTOLEX, DERMAGRAFT, BIAFINE Y APLIGRAF. Alli estan las referencias.
A partir del dia de hoy DERMAGIC sera montado en la lista ACADERM-L perteneciente al Dr. Art C Huntley, para su difusión en USA, una vez a la semana.
Hasta una próxima edición colegas,,, saludos,,,
Proximas ediciones: * ONICOMICOSIS BLANCA,,, * EL SOLARASE
1.) EDITORIAL /ENGLISH
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Hello friends, Dermagic again with you. They have left to the market several new products for the treatment of diabetic ulcer, the REGRANEX, CYTOLEX, DERMAGRAF, BIAFINE AND APLIGRAF. I, am sending the references on these products.
Starting from today's day DERMAGIC will be mounted in the list ACADERM-L belonging to the Dr. Art C Huntley, for their diffusion in USA, once a week.
Dermagic is also mounted in DERMLIST, Brazil, (Dr. George Leal), and FUNGI (Dr. Paulo Taborda), and diffused in Colombia, Peru, Argentina, Panama, Venezuela, etc.
Until a next edition colleagues,,,, greetings
Next editions: * WHITE ONYCHOMYCOSIS,,, * THE SOLARASE
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DERMAGIC/EXPRESS(16)
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U L C E R A D I A B E T I C A (II) //DIABETIC ULCER (II)
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ULCERAS EN LA WEB//ULCER IN THE WEB
1.) Cytolex Cream Heals Diabetic Foot Ulcers Well as
Oral Antibiotic
2.) FDA Panel Recommends Dermagraft For Diabetic Foot Ulcers
3.) Regranex Gel Approved In U.S. For Diabetic Foot Ulcers
4.) Biafine Now Packaged For Dermal Wounds And Radiodermatitis
5. FDA Advisory Panel Recommends Unconditional Approval of Apligraf TM for Treatment of Venous Leg Ulcers
6.)Ténica para la aplicación de Apligraf.//Technique to use APLIGRAF
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1.) Cytolex Cream Heals Diabetic Foot Ulcers Well as Oral Antibiotic
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PLYMOUTH MEETING, Pa., March 18, 1997 -- Magainin Pharmaceuticals
Inc. (Nasdaq: MAGN) today announced the successful results of its
second, pivotal Phase III clinical trial of Cytolex(TM) 1% topical
antibiotic cream (MSI-78) for the treatment of infection in diabetic foot ulcers.
The Company's analysis of the study showed statistical equivalence
between MSI-78 and orally administered ofloxacin, with respect to the
study's primary endpoint of clinical response of infection at day 10 of treatment,
and at subsequent time points through day 28, and at follow-up. Floxin(R)
(ofloxacin) is a quinolone antibiotic indicated for the treatment of skin and
soft tissue infections. The study enrolled 342 patients.
As a secondary endpoint, MSI-78 and ofloxacin were comparable with
respect to overall assessments of microbiological improvement.
Preliminary analyses of adverse events in the study suggest a
favorable profile for MSI-78. Both drugs were well tolerated, however, treatment with ofloxacin was associated with a significant excess of adverse events related to the central nervous system, particularly as it relates to insomnia.
Magainin previously announced successful results of its initial, pivotal trial of
MSI-78 for the treatment of infection in diabetic foot ulcers in September 1996.
"This is a strong confirmation of the efficacy and safety results observed in our
initial pivotal study," said Jay Moorin, Chairman, President and Chief Executive
Officer of Magainin. "Our two studies represent, to our knowledge, the largest
database of clinical data for infected diabetic foot ulcers that has been
assembled. If approved for marketing by the U.S. Food and Drug
Administration ("FDA"), we expect that MSI-78 will be the first antibiotic
specifically labeled for the treatment of infection in diabetic foot ulcers, and
will provide physicians an important alternative to systemic therapy."
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2.) FDA Panel Recommends Dermagraft For Diabetic Foot Ulcers
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LA JOLLA, CA -- January 29, 1998 -- The United States Food and Drug
Administration's general and plastic surgery devices panel of the medical
devices advisory committee has recommended that the agency approve
Advanced Tissue Sciences, Inc.'s Dermagraft(TM), a living human dermal
replacement for the treatment of diabetic foot ulcers, with the
condition that the company perform a post-marketing study.
Dermagraft is produced by culturing human dermal fibroblasts (a type of cell
commonly found in the dermal layer and in connective tissue) onto a
biosynthetic scaffold. As the fibroblasts proliferate on the scaffold,
they secrete important structural proteins and growth factors, generating
a three-dimensional human dermis. Dermagraft is then frozen for storage and shipment to the treating physicians for implantation into patients.
In the U.S., diabetic foot ulcers affect approximately 15 percent of the 16 million diabetic patients in their lifetime.
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3.) Regranex Gel Approved In U.S. For Diabetic Foot Ulcers
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RARITAN, NJ -- December 17, 1997 -- The United States Food and Drug
Administration (FDA) has granted marketing clearance for Regranex(R)
(becaplermin) Gel 0.01%, the first biologic proven to increase the
incidence of complete healing in diabetic foot ulcers.
When used as an adjunct to good ulcer care, Regranex Gel is indicated for
the treatment of lower extremity diabetic neuropathic ulcers that extend into the
subcutaneous tissue or beyond and have an adequate blood supply. Diabetic
foot ulcers are one of the most difficult types of wounds to heal. This new
Topical gel, which contains genetically-engineered platelet-derived growth
factor, is the first prescription biologic that actively stimulates the
body to grow new tissue to heal these wounds.
Clinical trials demonstrated that a once daily topical application of Regranex
Gel plus good ulcer care healed more diabetic ulcers than placebo gel plus
good ulcer care. Good ulcer care practices, including initial sharp debridement
(removal of dead tissue), daily dressing changes, pressure relief and treatment
of infection if present, are required to achieve the best results with Regranex
Gel. The product will be available in early 1998.
More than two million people with diabetes will develop foot ulcers
during their lifetime. Foot ulcers often go undetected since other ailments associated
with diabetes -- such as nerve damage and visual and circulatory problems -- make
it difficult for patients to feel or see the ulcer as it develops. These open sores
often don't heal and may lead to serious complications including severe
infection and amputation.
"Diabetic foot ulcers are a serious problem in this country, resulting in 67,000
amputations each year," said Mayer Davidson, M.D., president of the
American Diabetes Association. "Diabetic foot disease costs the nation more
than $1 billion each year."
"Wound healing is a complex process that, until now, only Mother Nature
could influence," said David Steed, M.D., professor of surgery, University of
Pittsburgh, and a clinical trial investigator. "Now, with Regranex Gel, we have
something that no drug has ever offered before, a simple, easy-to-use treatment
that actually stimulates the body to heal more diabetic ulcers."
Regranex Gel was well tolerated in all clinical trials. Incidence of adverse events
was similar in patients treated with Regranex Gel, placebo gel or good ulcer
care alone.
The active ingredient in the product is becaplermin, a genetically-engineered,
platelet-derived growth factor that mimics a protein that occurs naturally in the
body. The growth factor stimulates the migration of cells to the ulcer site, encouraging the patient's body to grow new tissue that heals these open wounds. becaplermin is produced by recombinant technology in yeast cells and is not derived from blood.
Regranex Gel was developed by the R.W. Johnson Pharmaceutical Research
Institute and will be marketed in the United States by Ortho-McNeil
Pharmaceutical, Inc.
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4.) Biafine Now Packaged For Dermal Wounds And Radiodermatitis
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WASHINGTON, MD. -- October 15 -- Medix Pharmaceuticals Americas,
Inc. said its wound management emulsion, Biafine(R), is now separately
packaged in the United States specifically for two applications: Biafine Wound
Dressing Emulsion (WDE) for the management of dermal wounds and burns
and Biafine Radiodermatitis Emulsion (RE) for protection against skin reactions
induced by radiation therapy and management of these reactions. The products
are cream emulsions, available without a prescription, that work by providing
an optimum environment for the skin's healing process.
The application of Biafine WDE and Biafine RE result in the recruitment of
macrophages to the wound site, which facilitate healing through all phases of the
healing process. Macrophage recruitment assists in debridement, the removal of
dead cells and tissue. Biafine's physical structure of oil in water also aids in the
removal of dead tissues and its emollient action helps liquify these tissues. The
emulsion provides a protective physical barrier against external contamination
as well as a moist environment and aids in the absorption of exudates, the fluids
that result from a wound.
Adequate hydration is essential to the healing process. Because its water
Content is highly available to the wound site, Biafine WDE and Biafine RE
provide deep dermal hydration: 41 percent of their water content is absorbed
deep in the skin within the first hour of application.
Biafine, a leading wound, radiodermatitis and burn care product in Europe, has
been used for more than two decades by physicians, fire departments,
emergency room personnel and radiation therapy facilities.
Healing results from a complex series of cellular and biochemical processes.
Macrophages are cells which aid the healing process in several ways, including
the removal of foreign particles and microorganisms. Macrophages occur in the
Walls of blood vessels and are usually immobile until stimulated by inflammation
resulting from a wound or infection.
The healing process consists of three phases: 1) inflammation, during which
macrophages assist in autolytic debridement, the removal of dead cells and
tissue debris from the wound site; 2) proliferation, in which macrophages
stimulate the production and activity of fibroblasts, cells responsible for the
production of materials essential to healing such as collagen; and 3) maturation,
when fibroblast proliferation promotes multiplication and growth of skin cells through chemical messengers such as fibroblast growth factor and macrophage-derived growth factor.
The unique formulation of Biafine recruits macrophages to the wound site
During all three phases.
Biafine WDE can be used for a variety of full and partial thickness dermal
wounds, including dermal, vascular, arterial, diabetic and pressure
ulcers, as well as first and second degree burns. The product is a fluid, yet firm,
emulsion that will conform to the contours of a wound and is available in 45-ml and
100-ml tubes. Biafine WDE can be used safely with topical antibiotics.
According to the most recent data available from the National Center for
Health Statistics, in 1992, there were a total of 34 million emergency room
visits that were injury-related, generating over $9.2 billion US in
healthcare costs. Wound care was performed at approximately one-third of these visits.
In addition to wounds resulting from surgery or injury, Biafine WDE can be
used for dermal ulcers, which are open sores on any external surface of the
body. Diabetics often suffer from dermal ulcers, usually on their feet. Biafine
WDE can also be used for pressure ulcers, known more commonly as
bedsores. Pressure ulcers occur in five to nine percent of all hospitalized
Patients and in 23 percent of all nursing home patients.
Biafine WDE can also be used for chronic or delayed healing wounds.
Application of Biafine WDE can renew the healing process in wounds that have
not yet healed for years.
In addition, Biafine WDE can be used for the management of first and second
degree burns. First degree burns are classified as those that involve only the
epidermis (outermost layer of the skin) and are most commonly the result of
overexposure to ultraviolet radiation, such as sunburn. Second degree burns
Are usually flash burns or the result of scalds.
Radiation therapy is used to treat many kinds of cancer in almost any part of
the body. One common side effect of radiation therapy is radiodermatitis, in
which the skin in the treatment area begins to look reddened, irritated or
burned. Radiation-treated skin may also develop a moist reaction, especially
where there are skin folds and may become very sore. Patients given radiation
therapy for breast cancer are especially at risk for radiodermatitis. Biafine RE is
available in 45-ml and 20-ml tubes as a prophylaxis against radiodermatitis and
for the management of the condition.
If a skin reaction occurs after radiation therapy, Biafine RE can be
applied as a wound dressing to manage radiodermatitis. In more severe cases of
radiodermatitis, it should be applied in thick layers and may be covered with a
gauze dressing if necessary.
PR Newswire 1998 Jan, 29
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5.) FDA Advisory Panel Recommends Unconditional Approval of Apligraf TM
for Treatment of Venous Leg Ulcers
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CANTON, Mass. (BW HealthWire/ via PRNewsWire/ via NoBlood.com) -
Organogenesis Inc.
(AMEX:ORG) today announced that the General and Plastic Surgery Devices
Advisory Panel to the Food and Drug Administration (FDA) recommended
unconditional approval of AppliGraf(TM) (Graftskin) Human Skin Equivalent
for the treatment of venous leg ulcers. Approximately one million people in
the United States -- four million globally -- suffer from venous leg
ulcers. Apligraf(TM) is the first manufactured living human organ --
multilayered skin -- to be recommended for approval by an advisory panel to the FDA.
All Panel members stated they were in favor of product approval. The Panel
members voted 5 to 4 in favor of approval of Appligraf(TM) without
conditions. In its pivotal trial, Apligraf(TM) was found to be highly
effective in the treatment of venous leg ulcers. The product was especially
effective in difficult-to-heal ulcers: Apligraf(TM) healed more than twice
as many ulcers open for a year or longer, and healed them faster, than
compression therapy.
Apligraf(TM) was approved for the treatment of venous leg ulcers in Canada
in 1997, and was launched there in August 1997 by Novartis Pharmaceuticals
Canada Inc. Novartis AG, the world's leading Life Sciences company, has
exclusive worldwide marketing rights to Apligraf(TM) and is pursuing other
international registrations for the product. Under the agreement,
Organogenesis manufactures the product and Novartis is responsible for all
sales and marketing activities, as well as post-marketing studies.
"We believe Apligraf(TM) will revolutionize the treatment of venous leg
ulcers," said Herbert M. Stein, Organogenesis' chairman and chief executive
officer. "The advisory panel's confidence in the product is encouraging,
and we are hopeful Apligraf(TM) will soon be available to the one million
Americans who suffer from these wounds."
"Apligraf(TM) is a truly novel product and we are pleased to have Novartis
leading the world-wide marketing effort," Stein added. "Novartis has
extensive experience introducing novel products, from implementing
effective medical education and marketing programs to securing
reimbursement. Such programs help establish a long-term business base."
"Novartis is delighted that the FDA advisory panel recommends that
Apligraf(TM) be approved for marketing," said David Epstein, Vice
President, Marketing and Sales, Specialty Business Sector for Novartis
Pharmaceuticals Corp. "We look forward to being able to offer Apligraf(TM)
to patients suffering with venous leg ulcers."
Apligraf(TM) has a unique profile most similar to human skin. The product
is bi-layered, with both an epidermis and dermis, composed of living human
epidermal (keratinocytes) and dermal (fibroblasts) cells. The cells are
organized as in skin: for example, the epidermal layer is fully
differentiated and includes the protective outer stratum corneum. This is achieved via
Organogenesis' patented organotypic cell culture technology, which allows
the cells to self-establish their optimal three-dimensional arrangement for
function, as they do in the body.
In the Apligraf(TM) pivotal trial, it was found that half of venous leg
ulcer patients have had their ulcer for a year or longer. It is believed
Apligraf(TM) is able to heal persistent ulcers unhealed with standard
treatment because the living cells in Apligraf(TM) are believed to actively
contribute to wound healing. In contrast, bandages must rely on the
patient's own wound healing abilities, which can be compromised in
persistently unhealed wounds.
Apligraf(TM) is applied directly to the wound, much the same way as a
conventional skin graft. However, as Apligraf(TM) does not require
harvesting skin from the patient, it does not require hospitalization. It
has been used in over 400 patients without rejection.
Apligraf(TM) use does not require ultra-cold storage facilities or complex
thawing regimens: the physician simply schedules the patient, orders the
product and Apligraf(TM) is delivered ready-to-use.
Treatment of venous leg ulcers is a scheduled, non-emergency procedure.
In addition to venous ulcers, Apligraf(TM) studies have been completed in
skin surgery wounds and burn wounds; data from these studies have been
published and/or presented. A pivotal trial is underway in diabetic ulcers
which is expected to complete in late 1998/early 1999. A pivotal trial in
pressure sores is anticipated to begin in the first half of 1998.
Organogenesis Inc. designs, develops and manufactures medical therapeutics
containing living cells and/or natural connective tissue components.
Organogenesis' product development focus includes living tissue
replacements, cell-based organ assist devices and guided tissue
regeneration scaffolds. In addition to Apligraf(TM), the company's product
portfolio includes the GRAFTPATCHsurgical product (cleared for marketing in
the United States), a cell-based liver assist device, a vascular graft for
coronary artery bypass procedures and a tissue filler product for female
urinary incontinence.
Statements in this press release which express the "belief", "anticipation",
"intention" or "expectation," as well as other statements which are not
historical fact, and statements as to product compatibility, design,
features, functionality and performance insofar as they may apply
prospectively, are forward looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995 and involve risks and
uncertainties. There can be no guarantee that the FDA will accept the
Advisory Committee's recommendation, or that it will render its decision
in a timely manner. The company's actual results may differ significantly
from the results discussed on this press release or in other
forward-looking statements presented by management. Factors that might
cause such a difference include, but are not limited to, development by the
company's competitors of new technologies or products that are more
effective than the company's, risks of failure of clinical trials,
dependence on and retention of key personnel, protection of proprietary
technology, compliance with
U.S. Food and Drug Administration regulations, continued availability of
raw material for the company's products, availability of product liability
insurance upon commercialization of the company's products, ability to
transition from pilot-scale manufacturing to full-scale commercial
production of products, uncertainty as to the availability of additional
capital on acceptable terms, if at all, and the demand for the company's
products, if and when approved.
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6.) TECNICA PARA LA UTTILIZACION DE APLIGRAF (The Stuart Maddin Skin
Therapy Letter ///Technique to use APLIGRAF
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Preparation of the wound bed, proper application of Apligraf, and patient
compliance with underlying therapy for underlying disease are probably
the most important determinants of clinical efficacy.1,2
What are the most important things to remember about preparing the
wound?1
1. Debride the wound bed so that it is as clean and free of fibrotic/necrotic
tissue as possible.
2. After debridement, cleanse the wound bed of debris by irrigating with a
sterile, non-cytotoxic saline solution. You may apply gentle pressure to stop
bleeding and/or use topical hemostatic agents prior to application.
3. Contain bacterial infection.
4. Control leg edema and heavy wound exudation with elevation and compression of the leg.
5. Implement appropriate therapies for underlying venous insufficiency.
Should antimicrobial agents be used prior to the procedure?
The commensals in venous leg ulcers are generally not associated with the kind
of frank infection that would preclude the application of HSE. If
necessary, oral, topical or injectable antimicrobial agents may be used for one week prior to application.1,2 Several commonly used burn wound antimicrobial agents
(including mafenide acetate, polymyxin B sulfate, nystatin and sodium
hypochlorite) may have a deleterious effect on HSE. Certain cytotoxic agents
(Dakin's solution, mafenide acetate, Scarlet Red dressing, tincoban, zinc
sulfate, povidone iodine solution and chlorhexidine) can destroy cellular components of skin and HSE, and following their use, the wound should be thoroughly
cleansed with physiological saline before application.1
Use of Apligraf
1. Apligraf is intended for single-use only. It should be kept on its tray on
the medium in an incubator (19-31°C) until ready for use. It remains viable
for up to five days from the moment it is sealed in the pouch.
2. Before opening the plastic container, check the pH of the mediumby
comparing the colour to the colours on the chart provided. The medium is
compromised if the colour is purple, and possibly contaminated if the colour
is yellow.
3. Handle the Apligraf as little as possible, and use sterile technique.
4. Do not allow the HSE to dry out after opening the package, and place it on
the wound bed within 30 minutes.
5. The dermal layer (the glossy layer closest to the medium in the
container) should be placed flush with the wound surface. The
epidermal layer (matte, dull finish) should be facing up, exposed to the air.
Express any trapped air.1 HSE must be trimmed to fit inside the edge of the ulcer margins.
6. If exudateis a problem, slits (pie-crusting) with a scalpel blade, punch
biopsies or shredding may help prevent the HSE from floating off the
surface of the wound. To prevent contamination, the holes should be made
after HSE has been removed from the media well.2
7. It is very important to immobilize the HSE in contact with the wound
bed. If securing of the HSE is not complete, staples, sutures or other
methods should be used to prevent shear or friction.2 For venous leg ulcers,
cover the HSE with a nonadherent primary dressing (e.g. Tegapore® or
Mepitel®), then apply a pressure bolster (rolled or folded gauze or a foam
plug) and cover the bolster with an elastic wrap/compression bandage.1
8. Within one week of application, HSE may appear translucent and
cellophane-like. The graft may degrade partially or completely
following the
initial application. Degraded HSE may appear yellow and gelatinous,
and its similarity to purulent exudate may lead to inappropriate
diagnosis of skin infection. In acute or fresh wounds, HSE appears
pinkish or whitish-opaque within 1-2 weeks.1
9. In most cases, one to two applications of HSE will be sufficient; in a
minority of patients, three applications may be necessary. Reapply within six
to eight weeks if less than 50% of the original wound area has closed, or if
the HSE has not completely adhered to the wound. Do not disrupt healing
tissue or adherent HSE, but gently remove nonadherent remnants of the
product.1
In a number of patients, a single application of HSE has converted
chronic or non-healing wounds to acute, more responsive wounds.
Following the initial application, it may be advisable to wait 8-12 weeks
before using a second HSE in order to determine whether or not wound
healing has been jump-started and to prevent unnecessary expense.3
Dr Gary Sibbald, Toronto
10.The primary dressing covering the HSE should be inspected and changed at
least once a week. Highly exudative wounds may require more frequent
changes.1
Information for Patients
Patients should be told to expect some scarring but, generally a return of
skin colour and a good cosmetic outcome.4
Venous leg ulcer patients should elevate their feet as much as possible for the
first week after application and the underlying venous disease managed
aggressively to prevent recurrence. After the ulcer has healed, they should wear
elastic compression stockings delivering 30-40 mm Hg of pressure and have
follow-up inspections every three months for one year. It is also
important that they maintain proper nutrition.1
One of the most exciting benefits of HSE therapy is its ability to
dramatically accelerate wound closure, up to two to three times faster
than conventional multilayer compression therapy. In the pivotal leg
ulcer study, HSE closed as many wounds by eight weeks as conventional
therapy did by six months and also resulted in a significantly greater
number of patients with 100% wound closure. These differences were
even more striking with particulary difficult to heal ulcers (larger or of
longer duration).
References
1.Data on file, Novartis Pharma AG.
2.Falanga V, Margolis D, Alvarez O et al. Rapid healing of venous ulcers
and lack of rejection with an allogeneic cultured Human Skin
Equivalent.
Submitted for publication.
3.Sibbald G. Personal communication. July, 1997.
4.Sabolinski ML, Alvarez O, Auletta M et al. Cultured skin as a'smart
material' for healing wounds: experience in venous ulcers.
Biomaterials1996; 17: 311-320.
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DATA-MEDICOS/DERMAGIC-EXPRESS No (16) 12/11/98 DR. JOSE LAPENTA R. DERMATOLOGO
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Dr. Jose Lapenta R.
Maracay, Venezuela
[email protected]
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