A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity

  Can this act as a stimulus for us to scientifically investigate  all those  home remedies  which were popular in  Indian  Tradition 

A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity

1. Freya Harrison^a, 
2. Aled E. L. Roberts^a, 
3. Rebecca Gabrilska^b,
4. Kendra P. Rumbaugh^b, 
5. Christina Lee^c, 
6. Stephen P. Diggle^a

+Author Affiliations

1. aCentre for Biomolecular Sciences, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom
2. bDepartment of Surgery, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas, USA
3. cSchool of English and Centre for the Study of the Viking Age, University of Nottingham, University Park, Nottingham, United Kingdom

1. Address correspondence to Freya Harrison, freya.andersdottir@gmail.com, or Stephen P. Diggle, steve.diggle@nottingham.ac.uk.

1. Editor Dianne K. Newman, California Institute of Technology/HHMI

 

Next Section

ABSTRACT

Plant-derived compounds and other natural substances are a rich potential source of compounds that kill or attenuate pathogens that are resistant to current antibiotics. Medieval societies used a range of these natural substances to treat conditions clearly recognizable to the modern eye as microbial infections, and there has been much debate over the likely efficacy of these treatments. Our interdisciplinary team, comprising researchers from both sciences and humanities, identified and reconstructed a potential remedy for Staphylococcus aureus infection from a 10th century Anglo-Saxon leechbook. The remedy repeatedly killed established S. aureus biofilms in an in vitro model of soft tissue infection and killed methicillin-resistant S. aureus (MRSA) in a mouse chronic wound model. While the remedy contained several ingredients that are individually known to have some antibacterial activity, full efficacy required the combined action of several ingredients, highlighting the scholarship of premodern doctors and the potential of ancient texts as a source of new antimicrobial agents.

IMPORTANCE While the antibiotic potential of some materials used in historical medicine has been demonstrated, empirical tests of entire remedies are scarce. This is an important omission, because the efficacy of “ancientbiotics” could rely on the combined activity of their various ingredients. This would lead us to underestimate their efficacy and, by extension, the scholarship of premodern doctors. It could also help us to understand why some natural compounds that show antibacterial promise in the laboratory fail to yield positive results in clinical trials. We have reconstructed a 1,000-year-old remedy which kills the bacteria it was designed to treat and have shown that this activity relies on the combined activity of several antimicrobial ingredients. Our results highlight (i) the scholarship and rational methodology of premodern medical professionals and (ii) the untapped potential of premodern remedies for yielding novel therapeutics at a time when new antibiotics are desperately needed.

Bactericins as novel antibiotics

Are bacteriocins underexploited? Novel applications for old antimicrobials.

Montalbán-López M1, Sánchez-Hidalgo M, Valdivia E, Martínez-Bueno M, Maqueda M.

Author information

Abstract

Bacteriocins are ribosomally synthesized (poly)peptides produced by almost all prokaryotic lineages. Bacteriocins from lactic acid bacteria (LAB) and bacteriocin-producer probiotic organisms have been thoroughly studied due to their wide spectra of action, the long-term use in food fermentations and the consideration of these microorganisms as beneficial for human beings. Most of the studies on the biotechnological application of diverse bacteriocins have been focused on their use as food preservatives, nisin being the prototype successfully used in alimentation. However, bacteriocins from LAB have demonstrated a remarkable potential as therapeutics for medical or veterinary uses, alone or in combination with classical antimicrobials. Their interest is even higher now that the resistance to the antibacterials used in therapeutics is growing. In this review we explore exciting opportunities for bacteriocin and probiotic applications, highlighting the possibilities for new and innovative research in order to give the necessary attention to this type of natural molecules that exhibit a great potential.

PMID:

 

21470151

Those Mustard seed Ribosomes and the latest x-ray crystallography and the Nobel prize

 When  we  were in  Medical school 3 decades ago   all we  knew was  there  are  theses  small  round structures  which are on the  rough endoplasmic reticulum called  ribosomes which had  a 30 and 50 sub ubits  and  theses are involved in protein synthesis.

we have come a long way in understanding the subcellular structures in 3 decades.

Seminal Work for 2009 Nobel Prize in Chemistry Conducted at Brookhaven Lab

Venkatraman Ramakrishnan and Thomas Steitz used BNL’s National Synchrotron Light Source to produce atomic-level images of ribosomes

Biographical Information on 2009 Chemistry Nobel Prize Winners

Ramakrishnan's high-resolution structure of 30S ribosomal subunit, based on data collected at NSLS, APS, and ESRF, published by Nature in 2000.

Venkatraman Ramakrishnan is a U.S. citizen. He was born in 1952 in Chidambaram, Tamil Nadu, India. He earned his Ph.D. in Physics in 1976 from Ohio University. He conducted research at a variety of U.S. institutions before joining Brookhaven National Laboratory’s Biology Department in 1983, earning tenure in 1990. In 1997, he left Brookhaven Lab for the University of Utah, but maintained a guest appointment and continued to use the National Synchrotron Light Source at Brookhaven until 2001, conducting research that contributed to this year’s Nobel Prize in Chemistry. He is currently a Senior Scientist and Group Leader in the Structural Studies Division, MRC Laboratory of Molecular Biology, Cambridge, UK.

vancomycin the 50 year old "NEW" Antibiotic

• Use of vancomycin

More than half a century ago, the compound now known as vancomycin was isolated from a soil sample collected deep in the interior jungle of Borneo. The isolation was performed by Dr. E. C. Kornfeld, an organic chemist at Eli Lilly, which had begun a major program to discover new antimicrobial agents with activity against staphylococci [1]. Although it had been only 15 years since the initial deployment of penicillin and the subsequent discovery of macrolides and tetracyclines, staphylococcal resistance to these compounds was already a major problem in hospitals throughout the world.

The soil sample from Borneo contained an organism (subsequently named“Streptomyces orientalis”) that yielded a compound in broth fermentation with a high degree of bactericidal activity against staphylococci. The initial compound was labeled 05865, and early laboratory studies showed that staphylococci failed to develop significant resistance to 05865 on serial passage in culture media containing the drug. Because of the growing menace of drug-resistant staphylococci, the US Food and Drug Administration essentially “fast-tracked” approval of compound 05865, which was subsequently given the generic name “vancomycin,” a term derived from the word “vanquish.”

"Because vancomycin was no longer patented by that time, it was not subjected to the intense marketing typically associated with antimicrobial agents. Nonetheless, the drug more than “sold itself” because of a very real clinical need. "

KEY POINTS

• Giving vancomycin by continuous infusion appears to offer no advantage over giving it every 12 hours.
• Therapeutic blood levels can be reached more quickly if a loading dose is given, but whether this offers a clinical advantage is unclear.
• The trough vancomycin serum concentration should be greater than 10 mg/L to prevent the development of resistance, and trough levels of 15 to 20 mg/L are recommended if the minimum inhibitory concentration (MIC) is 1 mg/L or higher.
• Whether S aureus is becoming resistant to vancomycin is not clear.
• The variable most closely associated with clinical response to vancomycin is the area under the curve (AUC) divided by the MIC (the AUC-MIC ratio), which should be greater than 400

IN THE PAST HALF-CENTURY, vancomycin has gone from near-orphan status to being one of the most often used antibiotics in our formulary. The driving force for its use is clear: the evolution of Staphylococcus aureus. At first, vancomycin was used to treat infections caused by penicillin-resistant strains. However, the discovery of methicillin curbed its use for more than 2 decades.1

Then, as methicillin-resistant S aureus (MRSA) began to spread in the 1980s, the use of vancomycin began to increase, and with the rise in community-associated MRSA infections in the 1990s, it became even more widely prescribed. The recent Infectious Diseases Society of America (IDSA) guidelines for treatment of infections due to MRSA are replete with references to the use of vancomycin.2

Another factor driving the use of vancomycin is the increased prevalence of device-associated infections, many of which are caused by coagulase-negative staphylococci and other organisms that colonize the skin.3 Many of these bacteria are susceptible only to vancomycin; they may be associated with infections of vascular catheters, cardiac valves, pacemakers, implantable cardioverter-defibrillators, orthopedic implants, neurosurgical devices, and other devices.

To use vancomycin appropriately, we need to recognize the changing minimum inhibitory concentrations (MICs), to select proper doses and dosing intervals, and to know how to monitor its use. Despite more than 50 years of experience with vancomycin, we sometimes find ourselves with more questions than answers about its optimal use.

THE NEXT EPIDEMIC BEGINS

 After seeing  the various   Extremist islamic  terrorist attacks  recently in Europe and  USA   we are forgetting something


Day 1 A 34-year-old New Hampshire expectant mother visits her doctor’s office complaining of severe stomach pain, vomiting, diarrhea, fever, and chills. She is diagnosed with an intestinal infection, given intravenous fluids and a prescription for a fluoroquinolone—an antibiotic—and is sent home.

 Day 2 At a Massachusetts hospital’s emergency room, a 2-year-old boy with a severe case of diarrhea, vomiting, dehydration, and fever is given fluids and administered a cephalosporin, another type of antibiotic, and is admitted to the hospital.

 Day 4 The boy’s lab results come back identifying the cause of his illness as Salmonella, a common foodborne bacterial infection, but, in this instance, the “bug” is highly resistant to the antibiotics commonly used to treat such infections, including cephalosporins and fluoroquinolones. The baby boy dies of dehydration and bloodstream infection. As for the 34-year-old woman, the Salmonella infection results in a miscarriage of an otherwise normal baby followed by the woman’s death.

Day 5 325 people are dead. Thousands—many of them children, the elderly, and other vulnerable individuals—jam emergency rooms across the Northeast complaining of similar symptoms. Cases have been reported in 15 states along the East Coast and in the Mid-Atlantic region. Isolated cases are reported in other states, including Texas and California. Fourteen cases are reported in Mexico and 27 cases in Canada.

 Day 6 1,730 deaths and 220,000 illnesses have occurred in the United States. The epidemic expands in other countries. Canada, Mexico, and Europe close their borders to U.S. food imports, and travel initiated from the United States is banned around the globe. Economic losses to the U.S. and global economies soon reach tens of billions of dollars. The Food and Drug Administration and Centers for Disease Control and Prevention identifiy the source of the infections as a milk distribution facility located in New York state. They confirm that the Salmonella not only causes severe illness, but also is resistant to all available antibiotics. Doctors can only provide supportive care, not specific, antibiotic treatment.

 Day 7 The number of deaths and illnesses continues to climb. Think it can’t happen? Think again. In 1985, milk contaminated with Salmonella typhimurium infected 200,000 people across the Midwest. What distinguishes that case from our scenario is the development of a fully antibiotic-resistant strain of the bacteria as compared to the one that is only partially drug-resistant. Such “bad bugs” are evolving. Some are already here. Had bioterrorism prompted this scenario, infection rates could have been significantly higher, as several sources could have been intentionally contaminated. The toll on human lives and the U.S. economy would have been substantially worse.Can we avert this catastrophe? If we act now, the answer is yes.

Did Chloramphenicol get simply bad press and bad science

"DOUBLE TYPHOID" was a dreaded diagnosis in the  60s in India. My younger brother who was probably 12 or 13 years old  went to visit my  Uncle in Culcutta and  when he came back had a very high fever.
the use of  Double typhoid was interpreted by different people differently.
for some it was  a relapse  of the  same typhoid  with in shoe rt time  of getting over the first infection  for other it was  an infection  from   typhi and  para typhi infection in the same patient.
Any way  at that time  only Chloramphenicol  was the  effective antibiotic  available for typhoid fever  treatment.
  He  suffered  for  quite a few days  with high fevers  before recovering.

he had  a big growth spurt after this fever  infact he  is the  tallest and heaviest of all us  4 brothers.
 Chloramphenicol was supposedly associated with this deadly  disease called  aplastic anemia. so  after  lot of  controversy and discussion this drug  was almost banned in  most countries  and   we lost   a good weapon against the  most common of  infectious diseases  in  developing countries.

I always wondered  why  no other formulations  with the similar structure as  chloramphenicol were ever introduced .



"antique case reports leave doubt as to whether marrow failure in benzene workers was not often myelodysplasia rather than aplastic anemia. Unpredictable marrow failure in the setting of routine medical drug use is devastating to the patient and physician and has serious legal ramifications in pharmaceutical development. The study of idiosyncratic drug reactions, by definition so extremely rare, is difficult. That genetic differences in drug metabolism, especially in detoxification of reactive intermediate compounds, likely underlie susceptibility is thus poorly supported by experimental data. Overrepresentation of deletions in the drug metabolizing glutathione-S-transferase genes (GSTM1, GSTT1, which would increase concentrations of toxic drug intermediates) have been observed in some series.7,8 Nevertheless, no satisfactory mechanisms have been developed for the most notorious pharmaceutical, chloramphenicol, or for other heavily inculpated agents such as penicillamine or gold. Many drugs on “black lists” also more commonly cause mild marrow suppression. Regular but only modest destruction of marrow cells may sometimes be a prerequisite for a much more infrequent immune response to an exposed neoantigen. There is little demographic or clinical difference between patients with idiopathic aplastic anemia and those with an assumed drug etiology. Claims of permanent aplastic anemia after idiosyncratic exposure to minuscule quantities of chloramphenicol, as in ophthalmic solutions, may reflect observation and reporting biases rather than extreme sensitivity to a hidden metabolite. Conversely, very few chemotherapeutic agents, despite being designed as cell poisons and administered in milligram or gram quantities, directly result in irreversible marrow destruction without obvious effects on other organs.

If one takes a look at the case of vancomycin
We can realize that  some  toxic byproducts were the reason for the  toxicity of earlier versions of vancomycin so much so this drug was   discarded  as an antibiotic . it was  taken off the shelf dusted  and  manufactured  in  a more pure form and  it is now one of  the  live  saving  Antibiotics.

"Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future."

read the full article here 

AN OLD FRIEND REVISITS: CHLORAMPHENICOL OPTIC NEUROPATHY

Abstract

"A 66-year-old woman presented in October 2011 with bilateral visual failure of subacute onset. She has Rheumatoid Arthritis, treated with methotrexate (since 2002), etanercept (2003–2009). A right knee replacement was revised and underwent 6 washouts for persistent infection. Antibiotics included vancomycin, amoxicillin, and daptomycin. Chloramphenicol 4 g daily was started in June 2011 (14 weeks before visual loss). 10 days after onset of visual loss she had visual acuity of 3/24 (Snellen) bilaterally, hyperaemic optic discs and centrocaecal scotomas. The control Ishihara plate could not be read. Toxic optic neuropathy secondary to chloramphenicol was suspected; chloramphenicol had been stopped on Day 6 of visual symptoms. 4 weeks after stopping chloramphenicol acuity was 6/5 (right), 6/6 (left) and visual fields normal, but Ishihara colour plates impaired at 8/13 bilaterally. At the onset of visual symptoms she developed paraesthesiae of limbs which also improved. Examination showed L5 dermatomal loss to pinprick and abnormal proprioception at the toes. From 1950 to 1988 approximately 40 cases of chloramphenicol optic neuropathy were reported, but only two in the past 12 years. This case highlights the potential pitfalls of older generation antibiotics and unfamiliar adverse effects. This may become more pertinent as antibiotic resistance increase."


I was happy to see this article

Synthesis and evaluation of chloramphenicol homodimers: molecular target, antimicrobial activity, and toxicity against human cells.

let us hope one of the grandchildren of chloramphenicol will save our great grandchildren

SKIN TYPES

 I have always wondered how  anyone can forget about a billion people of this world when they are talking about the world population in general.

Specially during the latest election circus
"Judeo christian" what about atheists, Hindus,Buddhists,sikhs,Zoroastrians ,Jains,ismailis,Nirankaris ,bahais, Scientologists etc etc

then  let us see if  Health care  is any more   scientific and  less biased .
NO

looks  nonracial, but is not found to be useful by  Aesthetic surgeons.

Fitzpatrick classification of skin type

I Always burns never tans
 II Burns easily, tans with difficulty
III Rarely burns, tans easily
IV Never burns, tans

Lancer ethnicity scale (LES) Geography Fitzpatrick skin type LES skin type

African background

Central East, West African V 5 Eritrean and Ethiopian V 5 North African, Middle East V

5 Arabian background Sephardic Jewish III

4 Asian background Chinese, Korean, Japanese, Thai, Vietnamese IV

 4 Filipino, Polynesian IV

4 European background Ashkenazi Jewish II

3 Celtic I 1 Central Eastern European III

2 Nordic I–II 1 Northern European (general)

I 1–2 Southern European, Mediterranean II

I 3–4 Latin/Central/South American background Central/South American Indian IV

 4 North American background Native American (including Inuit) II 3

this guy forgets (ignores) 1.75 billion  south Asians 

The only  classification which(is not yet adapted ) 

gives prominence to Indian skin type is  the following

is 

Table 3.3 World classification of skin type

1. European/Caucasian                         —white (a) Pale, cannot tan, burns easily, no

                                                                             postinflammatory pigmentation

                                                                               (b) Tan, rarely burns, rarely develops

                                                                                postinflammatory pigmentation

                                                                         (c) Deep tan, never burns, develops

                                                                               postinflammatory pigmentation

2. Arabian/Mediterranean/Hispanic—light brown (a) Pale, cannot tan, burns easily, no

                                                                              postinflammatory pigmentation

(b) Tan, rarely burns, rarely develops

postinflammatory pigmentation

                                                                                                (c) Deep, tan never burns, develops

postinflammatory pigmentation

3. Asian—yellow                                                              (a) Pale, cannot tan, burns easily, no

postinflammatory pigmentation

(b) Tan, rarely burns, rarely develops

postinflammatory pigmentation

(c) Deep tan, never burns, develops

postinflammatory pigmentation

4. Indian—brown                                                             (a) Pale, cannot tan, burns easily, no

postinflammatory pigmentation

(b) Tan, rarely burns, rarely develops

postinflammatory pigmentation

(c) Deep tan, never burns, develops

postinflammatory pigmentation

5. African—black                                                              (a) Pale, cannot tan, burns easily, no

postinflammatory pigmentation

(b) Tan, rarely burns, rarely develops

postinflammatory pigmentation

(c) Deep tan, never burns, develops

postinflammatory pigmentation



"pigmentation response occurs. It is hoped that this chapter will stimulate a lively scientific discussion that will take surgical dermatology from “Caucasian-centric” to multiracial. The development of a new classification of skin type will allow physicians of all races to treat patients of all races with techniques specific for the particular race being treated. Equally important would be to more completely r"

from  Simplified facial rejuvination

We are the majority!

The approximately 3.5 billion nonwhite people in India, China, Northeast and Southeast Asia, the Middle East, Spain, Central and South America, and the black populations of African countries, the USA and elsewhere represent the majority of the world’s human population.

Then  why do we allow theses  pink skinned people to  rule the world.
 The security council of UN
 The NSG
 G8
World bank
IMF

any and every  medical /scientific society which makes the rules which are followed by  the majority of the  population.


Just Think about it 

India bans fertility drug Letrozole what are the politics involved ? was it just "Group Think"

Conclusion: There was no difference in the overall rates of major and minor congenital malformations among newborns from mothers who conceived after letrozole or CC treatments. However, it appears that congenital cardiac anomaly is less frequent in the letrozole group. The concern that letrozole use for ovulation induction could be teratogenic is unfounded based on our data. (Fertil Steril 2006;85:1761–5. ©2006 by American Society for Reproductive Medicine.)

Finally, expert panel bans fertility drug Letrozole

Kounteya Sinha, TNN | Oct 18, 2011, 02.50AM IST

NEW DELHI: India has banned manufacture, sale and distribution of controversial drug Letrozole.

Though globally the drug is used for treatment of breast cancer, in India it was being administered to young infertile women to help them conceive.

A 16-member committee, under special director general of health services Dr D C Jain, decided to ban the drug.

The Union health ministry's notification on Monday said, "In exercise of the powers conferred by Section 26A of the Drugs and Cosmetic Act, 1940, the Central government has suspended the manufacture for sale, sale and distribution of Letrozole for induction of ovulation in anovulatory infertility with immediate effect. The Central government is satisfied that it is necessary and expedient to regulate by way of suspension of manufacture, sale and distribution of the drug for the said indication in the public interest."

It added, "The Central government is satisfied that the use of the drug for induction of ovulation in an ovulatory infertility is likely to involve risk to human beings and safer alternatives to the said drugs are available."

Over the years, there has been a growing suspicion that the drug's side-effects have led to severe genetic abnormalities among babies born to infertile women.

Dr Chandra M Gulhati, editor of Monthly Index of Medical Specialties, India, a journal on drugs, said, "Letrozole sold under various brand names in India such as Letroz and Letoval is internationally approved for treatment of breast cancer in post-menopausal women. Both, the Canadian drug regulator and the innovator company Novartis have warned gynecologists not to misuse it for female infertility. Research on 150 pregnancies has shown that babies born to mothers who had consumed Letrozole to increase fertility have suffered from bone malformations, cardiac stenosis and cancers."

Dr Gulhati added that Letrozole has a Rs-37 crore market in India, which is growing at 35% annually. Brands like Letroz and Letoval, made by Sun Pharma, are in great demand. While, minor players are Oreta (Dr Reddys), Letz (Chemech) and Shantroz (Shantha Biotech).

Ministry sources said the committee that took the decision included gynecologists, reproductive biologists, pharmacologists and research experts.

Dr Gulhati said "It is no more the first drug of choice for breast cancer as several new ones are now available. But, it still has a big market. This clearly shows how Letrozole's use for inducing ovulation is still rampant in India."

Edmonton Journal (Alberta)
November 30, 2005 Wednesday
Final Edition
Cancer drug linked to birth defects: Doctors warned to stop using Femara for infertility

BYLINE: Sharon Kirkey, CanWest News Service

SECTION: BODZ & HEALTH; Pg. A17

LENGTH: 510 words

Canadian doctors are being told to stop using a breast-cancer drug to help infertile women get pregnant because it could cause birth defects.

Femara is being used to induce ovulation in infertile women, even though the labelling and prescribing information clearly shows it should not be used in women who may become pregnant because of the potential risk to the mother and fetus.

But the pills were rushed to infertility clinics two years ago after reports showed Femara was better than some older fertility drugs at stimulating a woman's body to release eggs.

A study of 150 babies born to women who were treated with Femara at a Montreal fertility centre found a higher incidence of loco-motor malformations -- such as problems crawling or walking -- and heart anomolies compared to "normal" deliveries.

The study, which involved babies born at Montreal's St. Mary's Hospital between 1995 and 2004, was presented at a recent meeting of American and Canadian fertility specialists. The Montreal doctors concluded use of Femara to treat infertility "should be controlled until more data on the outcomes of pregnancies is obtained."

A leading Canadian fertility doctor said it's not clear if Femara caused the birth defects, or whether they were due to the underlying condition.

The drug has never been properly tested for wide-scale use as a fertility drug, said Dr. Roger Pierson, past president of the Canadian Fertility and Andrology Society and chair of its communications committee.

"What you don't want is everybody and their fellow doctor running out and doing this in an uncontrolled fashion."

In the 12-month period ending Oct. 31, 85,733 prescriptions for Femara were filled in Canadian retail drugs stores, according to IMS Health, which tracks prescription drug sales in Canada.

The drug's manufacturer and Health Canada have issued a "dear health care professional" letter reminding doctors Femara has not been approved for ovulation induction. The drug has been approved to treat advanced breast cancer in postmenopausal women.

"Novartis is aware that Femara (chemical name, letrozole) has been or is being used to treat infertility even though statements in the Canadian Product Monographs warn physicians about potential embryo- and fetotoxicity with or without teratogenicity" -- meaning the ability to cause birth defects, Novartis Pharmaceuticals Canada Inc. said in the letter sent to Canadian gynecologists, obstetricians and infertility specialists.

According to Health Canada, there have been international reports of 13 women exposed to the drug while pregnant. Four involved "adverse outcomes" for the babies.

Three of the cases involved the "off label" use of Femara for infertility. Two of the women had spontaneous abortions and the third woman's baby was diagnosed with a type of cancer at one year of age.

In the fourth case, a baby girl of a woman who was treated with Femara for breast cancer while she was pregnant was born with a genital abnormality.

Novartis says any woman who becomes pregnant after taking the drug should contact her doctor.

LANGUAGE: ENGLISH

1. S.K. Goswami, T. Das, R. Chattopadhyay, J. Sawhney, J. Kumar, K. Chaudhury, et al.
2. A randomized single-blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: a preliminary report
3. Hum Reprod, 19 (2004), pp. 2031–2035

• Abstract

  Background: Use of letrozole, a selective inhibitor of aromatase, reduces the gonadotrophin dose required to induce follicular maturation. We evaluated whether incorporation of letrozole could be an effective low-cost IVF protocol for poor responders. Methods: A randomized, controlled, single-blind trial was conducted in the Assisted Reproduction Unit, Institute of Reproductive Medicine, Kolkata, India. Thirty-eight women with a history of poor ovarian response to gonadotrophins were recruited. Thirteen women (Let-FSH group) received letrozole 2.5 mg daily from day 3-7, and recombinant FSH (rFSH) 75 IU/day on days 3 and 8; and 25 women (GnRH-ag-FSH group) underwent long GnRH agonist protocol and stimulated with rFSH (300-450 IU/day). Ovulation was triggered by 10 000 IU of HCG followed by IVF-embryo transfer. The main outcome measures were total dose of rFSH (IU/cycle), terminal estradiol (E2) (pg/ml), numbers of follicles, oocytes retrieved and transferable embryo, endometrial thickness (mm), and pregnancy rate. Results: Compared with the GnRH-ag-FSH group (2865 ± 228 IU), the Let-FSH group (150 ± 0 IU) received a significantly (P < 0.001) lower total dose of FSH. Except for terminal E2, which was significantly higher (P < 0.001) in the GnRH-ag-FSH group (380 ± 46 pg/ml) than the Let-FSH group (227 ± 45 pg/ml), the treatment outcomes in all other respects, including pregnancy rate, were statistically comparable. Conclusions: Adjunctive use of letrozole may form an effective means of low-cost IVF protocol in poorly responding women. © European Society of Human Reproduction and Embryology 2004; all rights reserved.