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Viagra for women? Drug
developed as antidepressant effective in treating low
libido
The
drug flibanserin, which was originally created as an
antidepressant, is effective in treating women with
low libido, pooled results from three separate
clinical trials have found.
These trials were the first ever to
test a therapy that works at the level
of the
brain to enhance libido in women reporting low
sexual
desire,
said John
M. Thorp Jr., M.D., McAllister distinguished
professor
of
obstetrics and gynecology at the
University
of
North
Carolina
at Chapel Hill
School of
Medicine
and the principal investigator for
North
America in the studies.
“Flibanserin was a poor
antidepressant,” Thorp said. “However, astute
observers noted that it increased libido in
laboratory animals and human subjects. So, we
conducted multiple clinical trials and the women in
our studies who took it for hypoactive
sexual
desire disorder reported significant improvements in
sexual
desire and satisfactory
sexual
experiences.
“It’s essentially a Viagra-like
drug for women in that diminished desire or libido
is the most common feminine
sexual
problem, like erectile dysfunction is in men,” Thorp
said.
Studies have shown that the
prevalence of
hypoactive sexual
desire disorder in the U.S. ranges from 9 percent to
26 percent of
women, depending on age and menopausal status.
Flibanserin is currently an investigational drug and
is available only to women taking part in clinical
trials.
The results reported here were
presented Monday, Nov. 16, at the
Congress of
the European Society for
Sexual
Medicine
in Lyon, France. The presentation was given by
Elaine E. Jolly, M.D., overall principal
investigator and a professor
at the
University
of Ottawa
in Canada.
Jolly, Thorp and colleagues
pooled data from four clinical trials
of
flibanserin conducted in the U.S., Canada and
Europe. A total
of 1,946 pre-menopausal women ages 18 and
older were randomized to receive either flibanserin
or placebo for 24 weeks, with 4 weeks
of
pre-treatment baseline measurement and 4 weeks
of
post-treatment follow-up.
Initially, four different dosing
regimens were used in the trials: 25 milligrams
twice a day, 50 milligrams once a day at bedtime, 50
milligrams twice a day and 100 milligrams once a day
at bedtime. The dosing regimens totaling 50
milligrams a day were not effective while the
regimens totaling 100 milligrams were. So, the
results being reported are from only three
of the
four trials and are based on the 100 milligrams once
a day dosing regimen only.
The trials measured mean changes
from baseline on the following six variables as
reported by the women each week: number
of
satisfying sexual
events (SSE), electronic diary (eDiary) desire
score, female
sexual function index (FSFI) desire domain
score, FSFI total score, female
sexual
distress scale-revised (FSDR-R), and FSDR-R Item 13
(which focuses specifically on desire/libido).
The researchers concluded that
treatment with 100 milligrams
of
flibanserin once a day was associated with
significant improvements versus placebo in the
number of
satisfying sexual
events (SSE) reported,
sexual
desire (as measured by eDiary and FSFI desire
domain), a reduction in distress associated with
sexual
dysfunction (as measured by FSDS-R and its Item 13),
and sexual
functioning as measured by FSFI.
“These results point to a novel
approach to pharmacologic treatment
of the
sexual
problem that plagues reproductive age women the
most, and may over time prove to be an effective
treatment without the side effects
of
androgen replacement therapy, which is the only
treatment currently available,” Thorp said.
The trials were funded by
Boehringer Ingelheim Pharmaceuticals, the
manufacturer of
flibanserin.
Source:
http://www.med.unc.edu/www/news/2009-news-archives/november/viagra-for-women-drug-developed-as-antidepressant-effective-in-treating-low-libido/
Cervical cancer link to early sex
Having sex at an early age has been linked with double the
risk of developing cervical cancer.
An investigation into why poorer women have a higher risk of
the disease found they tended to have sex around four years
earlier than more affluent women.
It had been thought that the disparity was due to low
screening uptake in poorer areas, but the study found this
was not the most important factor.
The latest findings are published in the British Journal of
Cancer.
Although the difference in cervical cancer incidence between
rich and poor - across the world - had been noted for many
years, it was not clear why this is the case.
Especially as rates of infection with human papillomavirus (HPV)
- the
sexually transmitted infection linked with the
vast majority of cervical cancers - seemed to be similar
across all groups.
The study, by the International Agency for Research on
Cancer, of nearly 20,000 women, confirmed that the higher
rates of cervical cancer were not linked to higher HPV
levels.
Although women can be infected by HPV at any age, infections
at a very young age may be especially dangerous as they have
more time to cause damage that eventually leads to cancer.
But what it did reveal is that the two-fold increased risk
was largely explained by women from poorer backgrounds
starting to have sex at a younger age.
The age at which a woman had her first baby was also an
important factor.
Screening was found to have some effect on the level of
risk.
But the number of sexual partners a woman has and smoking
did not account for any of the difference.
Study leader, Dr Silvia Franceschi, said the findings were
not restricted to
adolescence and the risk of cervical cancer was
also higher in women who had their first
sexual intercourse at 20 rather than 25 years.
"In our study, poorer women had become sexually active on
average four years earlier.
"So they may have also been infected with HPV earlier,
giving the virus more time to produce the long sequence of
events that are needed for cancer development."
Dr Lesley Walker, director of cancer information at Cancer
Research UK, said the study raised some interesting
questions.
"Although women can be infected by HPV at any age,
infections at a very young age may be especially dangerous
as they have more time to cause damage that eventually leads
to cancer.
"Importantly, the results back up the need for the HPV
vaccination to be given in schools at an age before they
start having sex, especially among girls in deprived areas."
Source: BBC news, 21 December 2009
Desire Drug May Prove Sex Really Is All in Her Head
Boehringer Ingelheim GmbH is banking on
sex really being all in women’s heads.
The German drugmaker is putting the finishing touches on a
pill designed to reawaken desire by blunting female
inhibitions. Unlike Viagra, which targets the mechanics of
sex by boosting blood flow to the penis, this drug works on
the brain.
The desire drug, the focus of a meeting on sexual disorders
in Lyon next week, has the potential to revolutionize sexual
medicine much as Pfizer Inc.’s blue pill did a decade ago.
That could put family-owned Boehringer at the center of a
debate about whether the medicine is a chemical shortcut
around a complex dysfunction involving body and mind -- or
whether disinterest in sex is a legitimate medical
condition.
“This drug has the potential to finally open the door to
acceptance of the idea that decreased desire can be
something that involves a dysfunctional way the brain works,
and not only a bad partner,” said Jim Pfaus, a neurologist
at Concordia
University in Montreal, who conducted early tests of the
drug in rats. “Of course it’s in your head.”
The U.S. market for medicines to rekindle female libido
could be bigger than the $2 billion a year in U.S. sales for
erectile dysfunction treatments because more women report
sexual problems, BioSante Pharmaceuticals Inc. Chief
Executive Officer Stephen Simes estimated last year.
Showing It Works
Boehringer, based in the German town of Ingelheim on the
Rhine’s west bank, was searching for a depression treatment
in the 1990s when it stumbled on the compound, called
flibanserin. By 2002, Boehringer found the drug wasn’t
lifting patients’ mood. The company says researchers were
startled when test subjects rated one measure of well-being,
sexual appetite, consistently higher than the others.
After what Pfaus described as an initial period of
hesitation about developing a sex pill, Boehringer decided
to move forward. The company needs new drugs because it
faces the loss of 1 billion euros ($1.5 billion) in annual
revenue when two older medicines, Mirapex for Parkinson’s
disease and Flomax to treat enlarged prostate, lose patent
protection next year.
The world’s largest closely held pharmaceutical company has
been studying flibanserin for more than a decade and it has
yet to publish clinical test results showing the drug is
effective. The company will lift its veil of secrecy on
Monday at the European
Society for Sexual Medicine conference with data from
trials of more than 5,000 European and U.S. women.
Women’s Distress
The main criterion for the clinical trials, which the
company named after flowers, was how many “satisfying sexual
events” women said they had experienced after starting
treatment. If the results are good, the so-called Bouquet
studies, dubbed Violet, Daisy, Dahlia and Orchid, could form
the basis for applications to U.S. and European regulators.
The German company is taking a page from Pfizer’s book. The
U.S. drugmaker broadened the appeal of Viagra in 1998 by
steering clear of the word “impotence” and saying the blue
pill addressed a disease called erectile dysfunction.
Boehringer is avoiding potentially offensive words such as
frigidity and refers to the problem its pill cures by its
clinical name, hypoactive
sexual desire disorder, or HSDD.
“An increasing body of evidence shows that hypoactive sexual
desire disorder causes substantial emotional distress,” said
Heike Specht, a spokesman for the company. The drugmaker
“has conducted late-stage clinical trials in over 5,000
women from which we hope will result the first available
pharmaceutical treatment.”
A
Boehringer survey of
31,000 U.S. women aged 18 and above found that one in 10
expressed distress because of diminished sex drive.
Ideological Battle
A
sluggish libido is “a real problem,” and early clinical
results so far suggest Boehringer’s drug can help, according
to Stephen Stahl, a psychopharmacologist and chairman of the
Neuroscience Education Institute in Carlsbad, California.
Stahl, who has been a consultant for Boehringer, sees a
growing role for drugs in treating sexual disorders.
Not everyone agrees there is a disorder to begin with.
In
2003, a year after Boehringer started the Bouquet clinical
trials, an article written by Ray Moynihan in the British
Medical Journal called female sexual dysfunction “the
freshest, clearest example we have” of a disease created by
pharmaceutical companies to make healthy people think they
need medicine.
“This is for some an ideological battle,” said psychiatrist
Michael Berner of theFreiburg
University Clinic, who had patients in Boehringer’s
studies. “One view is the multi-dimensional view you get
from people like me. And then you have these people that say
you should work only on relationship issues and that
medication cannot have a place.”
‘Like Dancing’
Researchers don’t know why some women’s libido falters, said
Pfaus, who has tested compounds in rats for Pfizer,
Boehringer and Palatin Technologies Inc. by gauging whether
they spur female rats to solicit sex from males.
“An erection is obvious, it’s easy,” Pfaus said. “But desire
-- how do you get at that?”
The explanation may be partly evolutionary, according to
Berner, who says male primates are driven by a need to
spread their semen, while for females it’s important to be
able to care for and rear the offspring.
Some researchers believe the social components of
intercourse mean that sexual problems can’t be addressed in
the same way as heart failure or cancer.
Sex is a “historical and cultural phenomenon,” said Leonore
Tiefer, a psychiatry professor at New
York University. There’s no baseline of normalcy by
which to define a disorder, she contends.
“It’s like dancing, or music, or piano-playing,” Tiefer
said. “You do it with the body, but the part the body plays
isn’t the largest part.”
Over the Wall
Flibanserin works on the brain by putting “two feet on the
brakes” to block the release of a chemical called serotonin,
which regulates mood, appetite, sleep and memory, Pfaus
said. In time, the process should trigger the production of
dopamine, a chemical that, among other jobs, helps stimulate
desire.
The drug differs from testosterone, a hormone that’s also
been tested to reawaken women’s desire. Berner, interviewed
at his study in Freiburg, sketched the picture of a wall to
explain how flibanserin works.
“You’re standing here, sad, inhibited,” he said, drawing a
stick figure next to the wall on a scrap of paper.
“Testosterone would give you a little bit more excitement,
so you’d climb over. Flibanserin would take away one of the
stones.”
Once a Day
The compound takes three to six weeks to kick in. The pill
has to be taken daily, and some women taking part in the
clinical trials reported feeling tired, Berner said.
Boehringer recruited women for clinical studies using print
advertisements. Berner said his patients were largely
professionals in their early 30s to mid-40s, and most chose
to continue in the trial in a subsequent phase that ensured
they would get the real drug instead of a placebo.
Boehringer is recruiting older women for a follow-up study.
Women can be diagnosed with hypoactive sexual desire
disorder if they feel concerned, bothered or frustrated by a
lack of desire -- or if it’s hurting their relationships.
The company used personal digital assistants to check
whether the pill was working. Participants were beeped once
a day and asked to rate their level of desire and say
whether they had been sexually active and whether it was
enjoyable.
Potential Rivals
If
flibanserin makes it to market, it will be the first success
after a series of failures from drugmakers including Procter
& Gamble Co. and Pfizer. The New York-based maker of Viagra
abandoned efforts to adapt its pill for women in 2004 and
closed sex-health research at the end of last year.
The only female sexual dysfunction therapy approved in the
U.S. is Eros-CTD,
from NuGyn, Inc., a suction pump that fits over the clitoris
much like the erection pumps that predated Viagra. Intrinsa,
a testosterone patch from Noven Pharmaceuticals
Inc. licensed by Procter & Gamble, is sold in Europe for
women whose uteruses have been removed. A U.S. version was
put on hold in 2004 on concern about whether it is safe for
long-term use.
Still in clinical trials are a new version of the P&G patch;
LibiGel, a testosterone gel from BioSante; and bremelanotide,
an injected therapy from Palatin Technologies.
Researchers around the world will be watching Boehringer’s
results in Lyon, according to Pfaus. “There are probably a
lot of companies holding their breath,” he said.
http://www.bloomberg.com/apps/news?pid=20601124&sid=a1dWw6lHCAJQ
The First Potential Treatment For
Premature Ejaculation
At the annual
meeting of the Sexual Medicine Society of North America (SMSNA),
Inc. in San Diego, Sciele Pharma, Inc., a Shionogi Company
and Plethora Solutions Limited, a wholly owned subsidiary of
Plethora Solutions Holdings PLC ("Plethora" AIM:PLE)., today
presented data from its second positive pivotal study of
PSD502 for the treatment of premature ejaculation (PE).
Results of the
double-blind treatment phase of this study, which enrolled
patients from the U.S., Canada and Poland, are consistent
with previously reported results of the pivotal trial
conducted in Europe and showed that men who were treated
with PSD502 five minutes before intercourse were able to
delay ejaculation up to five times longer than those who
used placebo.
Additionally,
patients and partners in both trials reported significant
improvements in sexual satisfaction, and the drug was well
tolerated.
An estimated
one-third of U.S. men ages 18 - 59 are affected by PE,
making it twice as prevalent as erectile dysfunction.
Currently, there are no prescription therapies approved in
the U.S. to treat PE.
PSD502, a
product in development for the treatment of PE, is a
proprietary formulation of the two marketed drugs lidocaine
and prilocaine dispensed by a metered dose aerosol. PSD502
works selectively on non-keratinized skin on the glans penis
(head of the penis).
"Premature
ejaculation can have a powerful negative impact on the
emotional and sexual lives of men and their partners," said
Professor Stanley E. Althof, PhD, Center for Marital and
Sexual Health of South Florida, West Palm Beach,
Florida.
"Recently, the
international
sexual health community agreed that PE should be
defined as ejaculation occurring within approximately one
minute of penetration that causes the patient distress. Now
we need to work to develop treatments, and these encouraging
results with PSD502 seem to be a step in the right
direction."
Both pivotal
trials showed clinically and statistically significant
efficacy in the treatment of premature ejaculation, as
measured by changes in Intravaginal Ejaculatory Latency Time
(IELT) and Index of Premature Ejaculation (IPE), a
patient-reported outcome of ejaculatory control, sexual
satisfaction, and distress.
"We are excited
that results from two pivotal studies have shown that PSD502
was effective for men with PE, and we look forward to the
opportunity to help patients who have had no real options to
date," said Patrick Fourteau, Chief Executive Officer of
Sciele Pharma, Inc.
"This data will
support the New Drug Application for PSD502 that we are
planning to submit to the U.S. Food & Drug Administration
(FDA), which upon FDA approval would make PSD502 be the
first prescription treatment in the U.S. for premature
ejaculation."
Pivotal
study details
The new study,
the second of two major pivotal trials, was designed to
assess the clinical benefit and safety of PSD502 in men with
PE.
The trial, which
randomized 256 patients across 38 investigational centers in
the U.S., Canada and Poland, also assessed the safety and
tolerability of the therapy.
Final analyses
of the 3 months data confirmed that PSD502 produced a
clinically and statistically significant increase from
baseline in all study primary and secondary endpoints.
The time for
IELT for PSD502 group increased 4.7-fold compared to
1.5-fold in placebo (p<0.0001), resulting in a geometric
mean IELT of 2.6 minutes in the PSD502 group and 0.8 minutes
in the placebo group.
There were
improvements in IPE scores in the PSD502 group, which
recorded patient and partner feedback, compared to placebo,
resulting in 5.0-, 4.6- and 2.5-point differences between
PSD502 and placebo in ejaculatory control, satisfaction and
distress domains, respectively (p<0.0001 between treatment
comparisons).
Overall, PSD502
was well-tolerated, with no serious adverse events reported
by patients or partners in the studies.
Also presented
for the first time at SMSNA were two subset analyses of the
European Phase III trial data showing:
-- Increased
ejaculatory latency and improvements in patent-reported
outcomes seen in the first month of use with PSD502 were
maintained over 2 to 3 months of treatment; and
-- A significant
positive correlation between mean IELT and IPE domain scores
after three months of treatment, indicating that increases
in IELT are associated with improvements in patient-reported
outcomes.
About
premature ejaculation
For years,
various experts debated on the true definition of premature
ejaculation. In 2008, the International Society for Sexual
Medicine presented an evidence-based definition of PE as
agreed upon by a consensus of the world's leading
sexual health experts: a male sexual dysfunction
characterized by ejaculation which always or nearly always
occurs prior to or within about one minute of vaginal
penetration, and inability to delay ejaculation on all or
nearly all vaginal penetrations, and negative personal
consequences, such as distress, bother, frustration and/or
the avoidance of sexual intimacy.
Source:
Medical News Today, 20 November 2009
Topical
erectile dysfunction therapy shows promise
An innovative
drug-delivery system – nanoparticles encapsulating nitric
oxide or prescription drugs – shows promise for topical
treatment of erectile dysfunction (ED) according to a new
study by scientists at Albert Einstein College of Medicine
of Yeshiva University.
The new system,
tested successfully on a small number of animals, could
potentially prevent side effects associated with oral ED
medications, if study results can be replicated in humans.
That could mean safer and more effective ED therapy for
millions of men with heart disease and other health problems
affecting erectile function. The study is published today in
the online edition of the Journal of Sexual Medicine.
Tens of millions
of men worldwide have benefited from oral ED medications
such as sildenafil (Viagra), vardenafil (Levitra), and
tadalafil (Cialis). However, these medications - which
belong to a class of drugs called phosphodiesterase type 5
(PDE5) inhibitors - have limitations. They can cause
systemic side effects that can be serious. These side
effects include headache, facial flushing, nasal congestion,
upset stomach, abnormal vision as well as isolated reports
of hearing and vision loss. Men who've recently suffered a
heart attack or stroke or have severe heart disease should
use these drugs with caution or not at all. In addition, "an
estimated 30 to 50 percent of men with ED do not respond to
oral use of PDE5 inhibitors," says senior author Kelvin P.
Davies, Ph.D., associate professor of urology at Einstein.
The
drug-delivery system, developed by Einstein scientists,
consists of nanoparticles – each smaller than a grain of
pollen – that can carry tiny payloads of various drugs or
other medically useful substances and release them in a
controlled and sustained manner.
The limited
number of topical formulations of ED drugs has so far proven
ineffective. This study was done to evaluate whether the
Einstein nanoparticles, which have been shown to penetrate
the skin, might allow the targeted delivery of compounds
that treat ED and thereby avoid the drugs' systemic effects.
An effective
topical therapy could be especially significant for those ED
patients – particularly men with diabetes – who have reduced
levels of nitric oxide (NO), the signaling molecule that
dilates blood vessels responsible for erectile activity.
These men, who often aren't helped by oral PDE5 inhibitor
drugs, may benefit from direct application of NO or the PDE5
inhibitors.
The
nanoparticles were tested on a total of 18 rats bred to have
age-related ED. The rats were divided into three treatment
groups. One group of seven rats received nanoparticles
encapsulating NO. A second group of five rats received
nanoparticles encapsulating NO plus an experimental ED drug
called sialorphin (which has a mechanism of action different
from PDE5 inhibitors). A third group of six received
nanoparticles encapsulating NO plus tadalafil (Cialis).
Five of the
seven rats treated with the NO-containing nanoparticles, and
all 11 rats treated with nanoparticles encapsulating NO plus
sialorphin or tadalafil showed significantly improved
erectile function. None of the seven rats in a control
group, which received empty nanoparticles, showed any
improvement.
"Most of the
animals, nearly 90 percent, showed a response to treatment
with the nanoparticles," says co-author Joel M. Friedman,
M.D., Ph.D., professor of physiology & biophysics and of
medicine. Dr. Friedman developed the nanoparticles with his
son Adam Friedman, M.D., chief resident in the division of
dermatology of the department of medicine at Montefiore
Medical Center, The University Hospital and Academic Medical
Center for Einstein.
"The response
time to the nanoparticles was very short, just a few
minutes, which is basically what people want in an ED
medication," adds Dr. Davies. "In both rats and humans, it
can take 30 minutes to one hour for oral ED medications to
take effect."
Postmortem
examination of the tissues at the site of administration
showed no signs of local inflammation or toxicity. "In
addition, when we applied the nanoparticles at therapeutic
doses, we found no indication of systemic side effects,"
says Dr. Friedman.
The Einstein
research team will carry out safety and dosing studies in
rats in the coming months. Clinical studies on humans could
begin in a few years if animal studies continue to show that
the nanoparticle delivery system is safe and effective. But
the investigators caution that the time from a
proof-of-concept trial in animals to approved use in humans
may be a decade or more.
source:
http://www.eurekalert.org/pub_releases/2009-09/aeco-ted091709.php
Topical Gel as an
Effective New Treatment
for Impotence
A gel applied to the
penis may be able to
help some impotent men
achieve an erection,
according to a study in
a recent issue of the
Journal of Urology.
However, many users
experienced an
uncomfortable sensation
and the potential
effects of the gel on
female partners is
unknown.
The gel contains a
hormonelike substance
called
alprostadil and an
agent known as SEPA that
helps deliver the
alprostadil through the
skin of the penis.
Alprostadil has
previously been shown to
enhance erections but
could only be
administered with an
injection. The topical
treatment may be another
option for impotence, or
erectile dysfunction,
a common, treatable
condition that affects
as many as 20 million
American men. Current
treatments for impotence
include oral
medications such as
Viagra (sildenafil),
injectable drugs, and
penile implants.
In the new study, a gel
containing either
alprostadil or a placebo
was applied to the penis
in 48 impotent men.
Overall, 67-75% achieved
an erection after using
the alprostadil gel
compared with 17%
applying the placebo
gel, report Kevin T.
McVary, MD, and
colleagues. McVary is an
associate professor of
urology at Northwestern
University Medical
School in Chicago.
No serious side effects
were seen, but nearly
all patients experienced
a warm sensation that
went away within 5-20
minutes of application
of either gel.
Approximately 20% of the
men that received the
alprostadil gel
described discomfort
along the penis. The
authors say it appears
that the alprostadil is
responsible for the
discomfort. No evidence
of serious skin
reactions was seen.
In an editorial comment
accompanying the study,
Geoffrey N. Sklar, MD,
points out that while
using a gel medication
for achieving erections
is an attractive
possibility, past
experience has shown
them to be largely
ineffective and have
many side effects.
"A central issue
surrounding this route
of administration is
whether patients will
accept discomfort when
using an
[erection-inducing]
agent," writes Sklar,
who is from the division
of urology at the
University of Maryland
School of Medicine in
Baltimore. He also
suggests that gathering
more information about
how patients use the gel
at home is important.
Sklar says that gel
medications may be a
useful alternative when
oral medications fail.
McVary says that with
regard to effects the
gel might have on female
partners, a South
American researcher
found only one incidence
of minor
vaginal bleeding in
studies of 18 women
whose partners used a
similar gel. "It's a
different drug, but the
same concept," he says.
McVary adds that the
topical alprostadil gel
is potentially useful
for virtually all types
of impotence since the
study included a broad
distribution of patients
with different causes
for their impotence.
Womb
transplantation to become a reality soon
British scientists have taken a step
closer to performing a womb transplant, reports reveal. At present,
women whose wombs are unable to sustain a pregnancy or who are born
without a womb only have surrogacy and adoption as options when
starting a family. Around 15,000 women of childbearing age are
thought to be in this position.
Now, experts at Hammersmith Hospital
in London have worked out how to transplant a womb with a sufficient
blood supply to support a growing baby.
Five rabbits were given donor wombs
using the new technique and subsequent examinations revealed that
the transplants had been successful.
Richard Smith, consultant
gynaecological surgeon at Hammersmith Hospital, commented: 'I think
there are certain technical issues to be ironed out but I think the
crux of how to carry out a successful graft that's properly vascularised - I think we have cracked that one.'
However, Tony Rutherford, chairman of
the British
Fertility Society, noted that there is a 'big difference'
between demonstrating the procedure in rabbits and transferring it
to larger animals or humans.
Source:
netdoctor.co.uk, 22 October 2009
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