SLA Biomedical & Life Sciences Division Blog

Cholera

It is almost exactly a year ago that perhaps the most wide-ranging review of the state of our knowledge on vibrio cholera was published in the prestigious journal Nature Reviews Microbiology  by Nelson et al (2009).  Given that Haiti is experiencing an incipient epidemic (see McNeil & Sontag 2010), it might prove useful to review the facts.

• Cholera is spread primarily by water contaminated by bacteria  known as Vibrio cholerae, although contaminated seafood, especially raw shellfish,  will give it to you as well.

 

• Cholera is overwhelmingly a disease of Third World countries with  overcrowded populations with poor isolation of water for drinking and cooking apart from water used to flush feces and wash clothes soiled by diarrhea.  Cholera is very frequent in Bangladesh (Emch et al 2010), southern India (Das 2010),  southeast Asia (Lenglet et al 2010) certain sub-Saharan African cities (Lusaka, see Gettlemen 2009), and parts of Latin America (Alamet et al 2010).  Eastern Europe and Russia are also susceptible when water and sewer infrastructure  crumbles  owing to age or poor maintenance (Cromley 2010). Crowding alone rarely provides sufficient conditions for cholera. Hong Kong & Singapore are tremendously crowded places, but sanitary systems have been updated and made robust enough to withstand certain shocks, so chances for cholera outbreaks there are reduced. Despite being located on a peninsula where cholera is endemic, Singapore, a city-state of 4.8 million people,  had only 7 cases of vibrio cholera  in 2007, and to the degree it can be confirmed, raw seafood seemed to be the primary culprit although contaminated beverages were also implicated  in one case (Wong, James & Goh 2010).

 

 

• Cholera is considered to be a perfect model for public health experts and mathematically inclined epidemiologists (Azaele et al 2010) to use to predict and map epidemics, owing to its having had repeated outbreaks over long periods of time, many of which were well  documented in terms of the number of victims, locations, weather conditions, and demographics (Bertuzzo et al 2010, Ruiz-Moreno et al 2010). Three factors in addition to poverty and overcrowding almost mathematically tend to predict outbreaks. 1.  Unusually heavy rains, which cause sewage and drinking water to mix (Sasaki et al 2009)  2. Spikes of high temperatures which favor the multiplication of the bacterium (Islam et al 2009).  3. Physical shocks such as earthquakes, volcanoes, tsunamis, and floods so deep that buried pipelines are crushed from overhead weight and/or dams break (Guha-Sapir & Gijsbert van Panhuis 2009). It is sadly  no surprise that earthquake-damaged Haiti is experiencing an epidemic, but almost astonishing  that cholera has not broken out to any extent in vastly more flooded Pakistan, which has experienced  many of these contributing factors but fortunately temperatures there are heading downwards in a way that may limit vibrio proliferation.

 

• Vibrio cholera typically has a sort of bullet-shaped or elliptical body, often developing  a whipping tail or flagellum that propels it. It uses the flagellum to penetrate membranes, and seems to thrive in those slick aquatic (but occasionally visceral) scummy surfaces that are called biofilms (Kamruzzaman et al 2010).

 

 

• The bacterium  otherwise has what amounts to a two step life cycle. It lives and reproduces relatively slowly in sewage-type water, but once a patient ingests as little a single glass of this sort of water  (unwittingly containing  millions to billions of unseen particles), it can begin a new and hyper-virulent  life cycle in the body, if it beats certain of the body’s defenses.

 

• Curiously the biggest initial defense is stomach acid (Nalin et al 1978). There is some evidence that a diet high in certain acidic foods or acidic natural products confers some disease resistance (Rahim et al 2010).

 

•  Once the bacteria survives to make it to the small intestine, it uses its flagella to propel the head of the bacterium into the lining of the small intestine. There  the bacterium’s “head”  release some toxins. These toxins cause the cells  lining the intestine to rupture and release free floating proteins, fats & carbohydrates,  which enable  the bacterium to feed and multiply very rapidly. In fact, once  the vibrio sustain an intestinal presence not only does the patient become very sick, but the bacteria that emanates from his or her stool become hyper-infectious, reproducing much more rapidly than in ordinarily contaminated water, and causing person-to-person transmission to happen more quickly and resulting  in the most severe of symptoms (Merrell et al 2002).

 

 

• Intestinal tissue damage, from marauding vibrio, however,  is not the immediate cause of death. Rather it is the massive diarrhea of a consistency and appearance of  what is typically described in the medical literature as “rice water:” i.e. Water that looks like it was left over after you had boiled rice in it. What that water contains, besides tens of  trillions of hyper-infectious vibrio is a great quantity of electrolytes (dissolved salts and trace minerals) without which the body cannot function, as well as vast quantities of water (sometimes quarts at a time) that have to be replaced or the patient will die of dehydration, which is ironic since it often seems as if the patients  are practically swimming in their own watery waste. 

 

• While antibiotics will help a patient, particularly if the right ones are matched to the right subtypes of cholera, the patient must first survive the onslaught of their  fluid and electrolyte loss through the immediate force-feeding of  oral rehydration therapy. The composition of the remedial solutions often consists of fairly simple concoction of water, salt, sugar, and well-cooked rice. The chances for recovery go  up from around 50% to as high as 99% if the patient is well hydrated through a crisis period lasting several days (Atia & Buchman 2010). It’s key, of course, that the water used to make these is uncontaminated!

 

• Certain age groups and people with certain blood types seem to have a special propensity for bad outcomes during cholera epidemics. Children under the age of 5 (Bryce et al 2005) , and people with blood type O are especially hard hit (e.g. Swerdlow et al 2005).

 

• What can be done to limit the spread or damage caused by vibrio cholera? While most vaccines developed to date are of limited effectiveness, a certain level of immunity is conferred if everyone is vaccinated in an endemic area, at least as long as the locally infective subtype does not mutate greatly ( Ali et al 2005).  The idea that we could release viruses that feed on vibrio into the local water supplies of an area undergoing an epidemic has some merit, since it has been found that seasonal outbreaks of cholera tend to be quashed when the viruses that feed on them also multiply to such a degree that they damp down the epidemic (Faruque et al 2005). But ultimately the most effective “cure”  for cholera is most likely to be industrialization which increases incomes for individuals and budgets for the local authorities while it  improves water supplies primarily for reasons of manufacturing, with its side benefit of building durable  separate  systems  for piping in and storing drinking water and processing and piping away urine and feces contaminated waste water  (Hamlin 2009). This complex, indirect, and largely capitalist approach surprisingly better explains long term successes in controlling outbreaks than theories of popular uproar, reform movements,  and grass roots public health outreach.


Tony Stankus FSLA [email protected]  Life Sciences Librarian, Science Coordinator, & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592 

Alam, Munirul, Suraia Nusrin, Atiqul Islam, Nurul A. Bhuiyan, Niaz Rahim, Gabriela Delgado, Rosario Morales, et al. 2010. Cholera between 1991 and 1997 in Mexico was associated with infection by classical, El Tor, and El Tor variants of Vibrio cholerae. Journal of Clinical Microbiology 48 (10) (10): 3666-74.

Atia, A, and A L Buchman. 2010. Treatment of cholera-like diarrhoea with oral rehydration. Annals Of Tropical Medicine And Parasitology 104 (6): 465-474.

Azaele, Sandro, Amos Maritan, Enrico Bertuzzo, Ignacio Rodriguez-Iturbe, and Andrea Rinaldo. 2010. Stochastic dynamics of cholera epidemics. Physical Review.E, Statistical, Nonlinear, and Soft Matter Physics 81 (5) (05): 051901-.

Bertuzzo, E., R. Casagrandi, M. Gatto, I. Rodriguez-Iturbe, and A. Rinaldo. 2010. On spatially explicit models of cholera epidemics. Journal of the Royal Society, Interface / the Royal Society 7 (43) (02/06): 321-33.

Bryce, J., C. Boschi-Pinto, K. Shibuya, & R./E. Black. 2005. WHO estimates of the causes of death in children. The Lancet 365: 1147-1152.

Cariri, F. A. M. O., A. P. R. Costa, C. C. Melo, G. N. D. Theophilo, E. Hofer, Melo Neto de, and N. C. Leal. 2010. Characterization of potentially virulent non-O1/non-O139 Vibrio cholerae strains isolated from human patients. Clinical Microbiology & Infection 16 (1) (01): 62-7.

Chowdhury, N., M. Asakura, S. B. Neogi, A. Hinenoya, S. Haldar, T. Ramamurthy, B. L. Sarkar, S. M. Faruque, and S. Yamasaki. 2010. Development of simple and rapid PCR-fingerprinting methods for Vibrio cholerae on the basis of genetic diversity of the superintegron. Journal of Applied Microbiology 109 (1) (07): 304-12.

Cromley, Ellen K. 2010. Pandemic disease in Russia: From black death to AIDS. Eurasian Geography & Economics 51 (2) (Mar): 184-202.

Das, Amitav, P. Manickam, Yvan Hutin, B. B. Pal, G. P. Chhotray, S. K. Kar, and M. D. Gupte. 2009. An outbreak of cholera associated with an unprotected well in Parbatia, Orissa, Eastern India. Journal of Health, Population, & Nutrition 27 (5) (10): 646-51.

Emch, Michael, Mohammad Yunus, Veronica Escamilla, Caryl Feldacker, and Mohammad Ali. 2010. Local population and regional environmental drivers of cholera in Bangladesh. Environmental Health: A Global Access Science Source 9 : 2.

Faruque, S.M. et al. 2005. Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages. Proceedings of the National Academy of Sciences of the United States of America 102: 1702-1707.

Gettleman, Jeffrey. 2009. Cholera epidemic follows drought in Kenya. New York Times (12/05): 1.

Goel, A. K., and S. C. Jiang. 2010. Genetic determinants of virulence, antibiogram and altered biotype among the Vibrio cholerae O1 isolates from different cholera outbreaks in India. Infection, Genetics & Evolution 10 (6) (08): 814-8.

Guha-Sapir, Debarati, and Willem Gijsbert van Panhuis. 2009. Health impact of the 2004 Andaman Nicobar earthquake and tsunami in Indonesia. Prehospital and Disaster Medicine: The Official Journal of the National Association of EMS Physicians and the World Association for Emergency and Disaster Medicine in Association with the Acute Care Foundation 24 (6) (2009): 493-9.

Hamlin, Christopher. 2009. "Cholera forcing". American Journal of Public Health 99 (11) (11): 1946-54.

Islam, M. S., M. A. Y. Sharker, S. Rheman, S. Hossain, Z. H. Mahmud, M. S. Islam, A. M. K. Uddin, et al. 2009. Effects of local climate variability on transmission dynamics of cholera in Matlab, Bangladesh. Transactions of the Royal Society of Tropical Medicine and Hygiene 103 (11) (11): 1165-70.

Kamruzzaman, M., S. M. N. Udden, D. E. Cameron, Stephen B. Calderwood, G. B. Nair, John J. Mekalanos, and Shah M. Faruque. 2010. Quorum-regulated biofilms enhance the development of conditionally viable, environmental Vibrio cholerae. Proceedings of the National Academy of Sciences of the United States of America 107 (4) (01/26): 1588-93.

Lenglet, Annick, Bouaphanh Khamphaphongphane, Phetsamay Thebvongsa, Phengta Vongprachanh, Noikaseumsy Sithivong, Chitsavang Chantavisouk, and Reiko Tsuyuoka. 2010. A cholera epidemic in Sekong Province, Lao People's Democratic Republic, December 2007-January 2008. Japanese Journal Of Infectious Diseases 63, (3): 204-207.

McLafferty, Sara. 2010. Placing pandemics: Geographical dimensions of vulnerability and spread. Eurasian Geography & Economics 51 (2) (Mar): 143-61.

McNeil, Donald G., and contributed reporting by Deborah Sontag. 2010. Cholera outbreak kills 150 in Haiti, raising fears of epidemic in crowded camps. New York Times (10/23): 5.

Merrell, D Scott, Susan M Butler, Firdausi Qadri, Nadia A Dolganov, Ahsfaqul Alam, Mitchell B Cohen, Stephen B Calderwood, Gary K Schoolnik, and Andrew Camilli. 2002. Host-induced epidemic spread of the cholera bacterium. Nature 417 (6889) : 642-645.

Nalin, D R, R J Levine, M M Levine, D Hoover, E Bergquist, J McLaughlin, J Libonati, J Alam, and R B Hornick. 1978. Cholera, non-vibrio cholera, and stomach acid. Lancet 2(8095) : 856-859.

Nelson, Eric J., Jason B. Harris, J. Glenn Morris, Stephen B. Calderwood, and Andrew Camilli. 2009. Cholera transmission: The host, pathogen and bacteriophage dynamic. Nature Reviews Microbiology 7 (10) (10): 693-702.

Pal, B. B., H. K. Khuntia, S. K. Samal, S. K. Kar, and B. Patnaik. 2010. Epidemics of severe cholera caused by El tor vibrio cholerae O1 Ogawa possessing the ctxB gene of the classical biotype in Orissa, India. International Journal of Infectious Diseases 14 (5) (05): e384-9.

Rahim, Niaz, Donald James Gomes, Haruo Watanabe, Sabita Rizwana Rahman, Chariya Chomvarin, Hubert Ph Endtz, and Munirul Alam. 2010. Antibacterial activity of Psidium guajava leaf and bark against multidrug-resistant Vibrio cholerae: Implication for cholera control. Japanese Journal of Infectious Diseases 63 (4) (07): 271-4.

Ruiz-Moreno, Diego, Mercedes Pascual, Michael Emch, and Mohammad Yunus. 2010. Spatial clustering in the spatio-temporal dynamics of endemic cholera. BMC Infectious Diseases 10 : 51.

Sasaki, Satoshi, Hiroshi Suzuki, Yasuyuki Fujino, Yoshinari Kimura, and Meetwell Cheelo. 2009. Impact of drainage networks on cholera outbreaks in Lusaka, Zambia. American Journal of Public Health 99 (11) (11): 1982-7.

Swerdlow, D., Mintz, E., Rodriguez, M., Tejada, E., Ocampo, C., Espejo, L., et al. (1994). Severe life-threatening cholera associated with blood group O in Peru: implications for the Latin American epidemic. The Journal Of Infectious Diseases, 170(2), 468-472.

Wong, C., Ang, L., James, L., & Goh, K. (2010). Epidemiological characteristics of cholera in Singapore, 1992-2007. Annals Of The Academy Of Medicine, Singapore, 39(7), 507-506.

 

The Bisphosphonates: Fosamax™, Actonel™, Actonel with Calcium ™, Boniva™, Atelvia™ , Reclast™, Skelid™ & Zometa™. Vastly more helpful for millions by reducing the threat of osteoporosis than surely more harmful for a very few

 

What are the bisphosphonates?

The bisphosphonates are a class of drugs that are generally prescribed, primarily for women who are late pre-menopausal, menopausal or post-menopausal to reduce and possibly reverse the demineralization of bone through calcium loss, usually targeting the two areas of the body where calcium loss causes the most damage: the spinal column (vertebrae) and the hip and thigh. They are also prescribed for certain cancers (mostly myeolomas, but also metastases from breast cancer in women and prostate cancer in men ), and diseases (Paget’s Disease, Osteogenesis Imperfecta,  AIDS, certain types of renal failure) which have the direct unfortunate effect of inducing bone thinning and fractures  of themselves, or which involve treatments that have those adverse side effects.

Why are these drugs  in the news?

On October 13, 2010, the US Food & Drug Administration added some new information to be given to patients taking these medications, as well as to their prescribing physicians. It concerns a potential for a somewhat higher statistical chance for certain rare types of hip and thigh bone fractures for those who have been taking bisphosphonates for several years vs. the overall incidence of vertebral, hip and thigh fractures.

Why would this be news?

It most likely became news primarily because we as a public in the United States and perhaps elsewhere in the developed world, have become almost paranoid about drug recalls, and are often morbidly entertained by conspiracy thinking about “Big Pharma” and doctors who prescribe drugs allegedly because they are incentivized with free vacations, subsidized continuing medical education junkets, or some other type of underhanded inducements. Less than a month earlier, Avandia™ , a drug given to diabetics to forestall heart disease (ironically diabetes is not the direct cause of death for the vast majority of diabetics, the number one direct killer of diabetics is actually heart disease) counter-intuitively actually increased the chances of a small, but significant number of Avandia™-taking patients, to develop heart disease, and therefore was severely restricted.

What actually did the FDA advisory say to patients about these bisphosphonates?

On its website, www.fda.gov/Drugs/DrugSafety/ucm229009.htm the FDA advises patients to:

• Continue to take your medication unless you are told to stop by your healthcare professional.

 

• Talk to your healthcare professional if you develop new hip or thigh pain (commonly described as dull or aching pain), or have any concerns  with your medications.

 

• Report any side effects with your bisphosphonate medication to FDA’s Medwatch program using the information at the bottom of the page in the “Contact Us” box.  

 

What did the FDA advisory say to Doctors about these bisphosphonates?

On its website, www.fda.gov/Drugs/DrugSafety/ucm229009.htm the “FDA recommends that healthcare professionals should:

• Be aware of the possible risk of atypical subtrochanteric and diaphyseal femur fractures in patients taking bisphosphonates.

 

• Continue to follow the recommendations in the drug label when prescribing bisphosphonates.

 

 

• Discuss the known benefits and potential risks of using bisphosphonates with patients.

 

 

• Evaluate any patient who presents with new thigh or groin pain to rule out a femoral fracture.

 

 

• Discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture.

 

 

• Consider periodic reevalutation of the need for continued bisphosphonate therapy, particularly in patients who have been treated for over 5 years.

 

 

• Report any adverse events with the use of bisphosphonates to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box.

 

Any information provided to MedWatch should be as detailed as possible and include information concerning fracture location/configuration, magnitude of trauma, fracture details (complete or incomplete, bilateral, or comminuted), presence and duration of prodromal thigh or groin pain, duration of bisphosphonate use, relevant medical history, and concomitant use of other medications. “

What is the key point involved in these advisories?

There appears to be a tiny  increase in the relative (but not necessarily absolute) number of subtrochanteric and femoral shaft fractures, largely  in elderly women taking one of the bisphosphonates for several years. Depending on your means of calculating odds with the worst case statistics, this means that there is a worst case possibility that 3%-5% of all the patients at high risk for an osteoporosis-related fracture might get a different and fairly rare (“atypical” is the term used) fracture farther down the thigh than the usual location for such fractures, and it would be wise to monitor them for dull pain in the thigh and/or groin  if they have been taking bisphosphonates for a long time (several years), because most patients (70%) who eventually have such a fracture had this tell-tale symptom first.

Does this mean that not taking bisphosphonates actually decreases your chance of getting a vertebral, hip  & thigh fracture?

Absolutely not! Probably the best estimate, taken from  Shane et al (2010) is that prescription bisphosphonates cut the number of vertebral fractures by 1000/10,000 patient years and the number of hip and thigh fractures by 700/10,000 patient years. This is an astonishingly positive  benefit to risk ratio. Quite literally millions of people have benefited from taking these drugs, while at the worst perhaps 300-400  cases drawn from about 170 pooled articles,  have been documented in the medical literature as having these rare fractures or other complications, in conjunction with their taking bisphosphonates .

Are there any confounding conditions connected with the women taking bisphosphonates and subsequently having one of these atypical fractures?

Yes, while the number of studies and case reports are scattered and do not all follow the same protocols for diagnosis and classification of these traumas, it appears, that a  fair number were older and  in generally poorer health, had been using proton pump inhibitors for gastric reflux,  had a history of osteoarthritis, had previous bone fractures and in some cases had taken cancer chemotherapeutic or immunosuppressive drugs. In other words, they had rather lengthy prior histories of medical importance. There is also some suggestion that Asian women were at greater risk.  However, other studies of women without all these complications or predispositions, or with matching records of having them to the same degree,  still show some increased risk of having these atypical fractures. There is little doubt that the risk of these atypical fractures is real, but significant doubt as to just how small the number of affected individuals might be when compared to the overall pool of people at risk for osteoporosis-related fractures: 5%?, 4%, 3%?, 2%?, 1%?,  0.1%, 0.01%? To determine better just what the odds are, and to track what happens when the bisphophonates are discontinued at the earliest signs of trouble, a registry of cases is being proposed (Shane et al 2010). Nonetheless, no fewer than 20 of the articles cited below still regard prescription bisphosphonates as the strategy of choice for patients seriously at risk for osteoporosis-related fractures.

What about bisphosphonates might be causing this small number of atypical fractures?

Fractures from osteoporosis related  causes tend to be  owing to the thinning  of the cortical (outermost) structural layer of bone, and/or from accumulating defects in the microarchitecture of the minerals in the bone. Bisphosphonates may be better at strengthening the cortical thickening than they are at repairing microarchitecture, or the methods or route  by which they strengthen the cortex has the unintended side-effect of further weakening the microarchitecture.  This microarchitecture  weakness would make help us make sense of the tiny minority of patients who also have a necrotic reaction to bisphosphonates that manifests itself in the jaw to the degree that it causes the drug’s discontinuance, and makes dental procedures problematic.  (But even in the cases of jaw misadventure, the patients are older, poorer, and sicker on average). In other words, bisphosphonates may not be the perfect medicine for this condition, albeit they are the best we currently have in production and have been proven safe and effective for millions thus far.

So, should we not be glad that the FDA stopped this "Big Pharma" conspiracy?

Well, even the worse conspiracy theorists would be dumbfounded when they learn that 21 of the 23 researchers involved in the key  Task Force of the American Society for Bone and Mineral Research overview (Shane et al 2010) on which the FDA’s modified patient and physician advisories were based,  either worked for, or had taken funding from, those allegedly evil folks in Big Pharma. It is little understood by many in the investigative reporting business that sometimes the greatest pool of expertise really does come from people who do research within or are funded by,   businesses who generally make our lives much better, because developing new drugs that help us manage or cure diseases is pretty much their life’s work.

What would be the most likely health outcomes if people were scared off taking their bisphosphonates by overhyped media reports?

Funny that you should ask, because a study of this has already been done in Australia where medical and prescription drug records are available to researchers owing to governmental benefits programs. According to Sambook et al 2010, adverse media reports on the side effects and risks for bisphosphonates appearing in Australia last year probably resulted in the ensuing nine months in 70 more hip fractures, 60 more other fractures (largely vertebral) and 14 more deaths, than would have occurred if the patients had simply stuck to taking them.

Tony Stankus FSLA [email protected] Life Science Librarian, Science Coordinator &  Professor,

Editor-in-Chief of Science & Technology Libraries

University of Arkansas Libraries MULN 233 E

365 North McIroy Avenue

Fayetteville, AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

Antoniazzi, Franco, Elena Monti, Giacomo Venturi, Roberto Franceschi, Francesco Doro, Davide Gatti, Giorgio Zamboni, and Luciano Tatò. 2010. GH in combination with bisphosphonate treatment in Osteogenesis Imperfecta. European Journal of Endocrinology / European Federation of Endocrine Societies 163 (3) (09): 479-87.

Baqain, Zaid H., Faleh A. Sawair, Zaid Tamimi, Nazzal Bsoul, Ghazi Al Edwan, Jamal K. Almasad, and Abdalla A. Abbadi. 2010. Osteonecrosis of jaws related to intravenous bisphosphonates: The experience of a Jordanian teaching hospital. Annals of the Royal College of Surgeons of England 92 (6) (09): 489-94.

Barney, Rocky J., Brian M. Wasko, Amel Dudakovic, Raymond J. Hohl, and David F. Wiemer. 2010. Synthesis and biological evaluation of a series of aromatic bisphosphonates. Bioorganic & Medicinal Chemistry 18 (20) (10/15): 7212-20.

Beukelman, T., K. G. Saag, J. R. Curtis, M. L. Kilgore, and M. Pisu. 2010. Cost-effectiveness of multifaceted evidence implementation programs for the prevention of glucocorticoid-induced osteoporosis. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (9) (09): 1573-84.

Bladé, J., M. T. Cibeira, de Larrea Fernández, and L. Rosiñol. 2010. Multiple myeloma. Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO 21 Suppl 7 (10): vii313-9.

Bleicher, Kerrin, Vasi Naganathan, Robert G. Cumming, Markus J. Seibel, Philip N. Sambrook, Fiona M. Blyth, David Le Couteur G., David J. Handelsman, Louise M. Waite, and Helen M. Creasey. 2010. Prevalence and treatment of osteoporosis in older Australian men: Findings from the CHAMP study. The Medical Journal of Australia 193 (7) (10/04): 387-91.

Body, J-J. 2010. Prevention and treatment of side-effects of systemic treatment: Bone loss. Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO 21 Suppl 7 (10): vii180-5.

Brandi, Maria Luisa. 2010. Current treatment approaches for Paget's Disease of Bone. Discovery Medicine 10 (52) (09): 209-12.

Brown, Janet E., and Sheryl Sim. 2010. Evolving role of bone biomarkers in castration-resistant prostate cancer. Neoplasia (New York, N.Y.) 12 (9) (09): 685-96.

Canoui-Poitrine, F., S. Jaglal, R. Chapurlat, V. Tainturier, C. Colin, and A. M. Schott. 2010. Has reimbursement of bone mineral density testing and anti-osteoporotic treatments improved management of osteoporosis in France? Bone 47 (4) (10): 790-4.

Cardwell, Chris R., Christian C. Abnet, Marie M. Cantwell, and Liam J. Murray. 2010. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA: The Journal of the American Medical Association 304 (6) (08/11): 657-63.

Castellví, Ivan, Maria Bonet, Jose Narváez A., and Jose Molina-Hinojosa. 2010. Successful treatment of SAPHO syndrome with adalimumab: A case report. Clinical Rheumatology 29 (10) (10): 1205-7.

D'Amelio, P., A. Grimaldi, M. A. Cristofaro, M. Ravazzoli, P. A. Molinatti, G. P. Pescarmona, and G. C. Isaia. 2010. Alendronate reduces osteoclast precursors in osteoporosis. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (10) (10): 1741-50.

Diel, Ingo J., Andreas H. A. Kurth, Hans-Bernd Sittig, Harald Meden, Michael Maasberg, Andreas Sandermann, and Raoul Bergner. 2010. Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer 18 (10) (10): 1305-12.

Dissette, Valeria, Pietro Bozzi, Carlo Alberto Bignozzi, Alessandro Dalpiaz, Luca Ferraro, Sarah Beggiato, Eliana Leo, Eleonora Vighi, and Luisa Pasti. 2010. Particulate adducts based on sodium risedronate and titanium dioxide for the bioavailability enhancement of oral administered bisphosphonates. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences 41 (2) (10/09): 328-36.

Duque, Gustavo, Jacqueline J. Close, Julien de Jager P., Peter R. Ebeling, Charles Inderjeeth, Stephen Lord, Andrew J. McLachlan, Ian R. Reid, Bruce R. Troen, and Philip N. Sambrook. 2010. Treatment for osteoporosis in Australian residential aged care facilities: Consensus recommendations for fracture prevention. The Medical Journal of Australia 193 (3) (08/02): 173-9.

Epstein-Barash, Hila, Dikla Gutman, Ela Markovsky, Galit Mishan-Eisenberg, Nickolay Koroukhov, Janos Szebeni, and Gershon Golomb. 2010. Physicochemical parameters affecting liposomal bisphosphonates bioactivity for restenosis therapy: Internalization, cell inhibition, activation of cytokines and complement, and mechanism of cell death. Journal of Controlled Release: Official Journal of the Controlled Release Society 146 (2) (09/01): 182-95.

Garg, Arun. 2010. News on bisphosphonates: But will patterns of use change? Dental Implantology Update 21 (9) (09): 71-2.

Gimsing, Peter, Kristina Carlson, Ingemar Turesson, Peter Fayers, Anders Waage, Annette Vangsted, Anne Mylin, et al. 2010. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): A double-blind, randomised controlled trial. The Lancet Oncology 11 (10) (10): 973-82.

Giovannini, Monica, Daniela Aldrighetti, Patrizia Zucchinelli, Carmen Belli, and Eugenio Villa. 2010. Antiangiogenic strategies in breast cancer management. Critical Reviews in oncology/hematology 76 (1) (10): 13-35.

Guañabens, Núria, and Albert Parés. 2010. Liver and bone. Archives of Biochemistry and Biophysics 503 (1) (11/01): 84-94.

Harel, Ran, and Lilyana Angelov. 2010. Spine metastases: Current treatments and future directions. European Journal of Cancer (Oxford, England: 1990) 46 (15) (10): 2696-707.

Haworth, Charles S. 2010. Impact of cystic fibrosis on bone health. Current Opinion in Pulmonary Medicine 16 (6) (11): 616-22.

Hofbauer, Lorenz C., Franz Jakob, and Dieter Felsenberg. 2010. Bisphosphonates and atypical femoral fractures. The New England Journal of Medicine 363 (11) (09/09): 1084; author reply 1084-5.

Holmberg, Anders R., Ulf H. Lerner, Ayodele A. Alayia, Mai Al-Mohanna, Chaker Adra, Marcela Marquez, Lennart Meurling, and Sten Nilsson. 2010. Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis. International Journal of Oncology 37 (3) (09): 563-7.

Iguchi, Kazuhiro, Yoshiki Tatsuda, Shigeyuki Usui, and Kazuyuki Hirano. 2010. Pamidronate inhibits antiapoptotic bcl-2 expression through inhibition of the mevalonate pathway in prostate cancer PC-3 cells. European Journal of Pharmacology 641 (1) (09/01): 35-40.

Imaz, I., P. Zegarra, J. González-Enríquez, B. Rubio, R. Alcazar, and J. M. Amate. 2010. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: Systematic review and meta-analysis. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1943-51.

Jones, Michael D., Charles W. Tran, Guang Li, Walter P. Maksymowych, Ronald F. Zernicke, and Michael R. Doschak. 2010. In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat. Arthritis and Rheumatism 62 (9) (09): 2726-35.

Jules, Joel, Jason W. Ashley, and Xu Feng. 2010. Selective targeting of RANK signaling pathways as new therapeutic strategies for osteoporosis. Expert Opinion on Therapeutic Targets 14 (9) (09): 923-34.

Kaji, H., Y. Kuroki, Y. Murakawa, I. Funakawa, Y. Funasaka, F. Kanda, and T. Sugimoto. 2010. Effect of alendronate on bone metabolic indices and bone mineral density in patients treated with high-dose glucocorticoid: A prospective study. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (9) (09): 1565-71.

Karosas, Ann O. 2010. Ewing's sarcoma. American Journal of Health-System Pharmacy: AJHP: Official Journal of the American Society of Health-System Pharmacists 67 (19) (10/01): 1599-605.

Katsumi, Hidemasa, Kosuke Kusamori, Toshiyasu Sakane, and Akira Yamamoto. 2010. Development of delivery system of bisphosphonates for the treatment of osteoporosis. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan 130 (9) (09): 1129-33.

Lamberg, A. L., E. Horvath-Puho, S. Christensen, and Sørensen H.T. 2010. Use of oral bisphosphonates and risk of venous thromboembolism: A population-based case-control study. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1911-7.

Lazarovici, Towy Sorel, Shlomit Mesilaty-Gross, Iris Vered, Clara Pariente, Hannah Kanety, Navot Givol, Ran Yahalom, Shlomo Taicher, and Noam Yarom. 2010. Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates. Journal of Oral and Maxillofacial Surgery: Official Journal of the American Association of Oral and Maxillofacial Surgeons 68 (9) (09): 2241-7.

Lipton, Allan. 2010. New approaches to treating and preventing bone metastases. Current Opinion in Supportive and Palliative Care 4 (3) (09): 178-81.

López-Jornet, Pía, Fabio Camacho-Alonso, Francisco Molina-Miñano, Francisco Gómez-García, and Vicente Vicente-Ortega. 2010. An experimental study of bisphosphonate-induced jaws osteonecrosis in sprague-dawley rats. Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 39 (9) (10): 697-702.

Lyritis, George P., Thomas Georgoulas, and Christos P. Zafeiris. 2010. Bone anabolic versus bone anticatabolic treatment of postmenopausal osteoporosis. Annals of the New York Academy of Sciences 1205 (1) (09): 277-83.

Magrey, Marina, and Muhammad Asim Khan. 2010. Osteoporosis in ankylosing spondylitis. Current Rheumatology Reports 12 (5) (10): 332-6.

Mahtani, Reshma, and Mohammad Jahanzeb. 2010. Bisphosphonates as anticancer therapy for early breast cancer. Clinical Breast Cancer 10 (5) (10/01): 359-66.

Maricic, Michael. 2010. The role of zoledronic acid in the management of osteoporosis. Clinical Rheumatology 29 (10) (10): 1079-84.

McKague, Meredith, Derek Jorgenson, and Kelly A. Buxton. 2010. Ocular side effects of bisphosphonates: A case report and literature review. Canadian Family Physician Médecin De Famille Canadien 56 (10) (10): 1015-7.

Mehanna, P., and R. Goddard. 2010. Bisphosphonate associated osteonecrosis: An unusual case. Australian Dental Journal 55 (3) (09): 311-3.

Miller, P. D., and R. J. Derman. 2010. What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1793-802.

Odri, Guillaume A., Sophie Dumoucel, Gaëlle Picarda, Sé Battaglia, François Lamoureux, Nadège Corradini, Julie Rousseau, et al. 2010. Zoledronic acid as a new adjuvant therapeutic strategy for Ewing's Sarcoma patients. Cancer Research 70 (19) (10/01): 7610-9.

Oldfield, Eric. 2010. Targeting isoprenoid biosynthesis for drug discovery: Bench to bedside. Accounts of Chemical Research 43 (9) (09/21): 1216-26.

Panzavolta, S., P. Torricelli, B. Bracci, M. Fini, and A. Bigi. 2010. Functionalization of biomimetic calcium phosphate bone cements with alendronate. Journal of Inorganic Biochemistry 104 (10) (10): 1099-106.

Pozzi, Samantha, and Noopur Raje. 2010. Bisphosphonates and atypical femoral fractures. The New England Journal of Medicine 363 (11) (09/09): 1083-4.

Rao, Shobha S., Nitin Budhwar, and Ambreen Ashfaque. 2010. Osteoporosis in men. American Family Physician 82 (5) (09/01): 503-8.

Reid, I. R., G. D. Gamble, P. Mesenbrink, P. Lakatos, and D. M. Black. 2010. Characterization of and risk factors for the acute-phase response after zoledronic acid. The Journal of Clinical Endocrinology and Metabolism 95 (9) (09): 4380-7.

Resnick, J., N. Gupta, J. Wagner, G. Costa, R. J. Cruz J., L. Martin, D. A. Koritsky, et al. 2010. Skeletal integrity and visceral transplantation. American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons 10 (10) (10): 2331-40.

Sambrook, Philip N., Jiang S. Chen, Judy M. Simpson, and Lyn M. March. 2010. Impact of adverse news media on prescriptions for osteoporosis: Effect on fractures and mortality. The Medical Journal of Australia 193 (3) (08/02): 154-6.

Schousboe, J. T., B. E. Dowd, M. L. Davison, and R. L. Kane. 2010. Association of medication attitudes with non-persistence and non-compliance with medication to prevent fractures. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1899-909.

Sellmeyer, Deborah E. 2010. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA: The Journal of the American Medical Association 304 (13) (10/06): 1480-4.

Shabestari, Ghasem Omati, Yadollah Soleimani Shayesteh, Arash Khojasteh, Marzieh Alikhasi, Neda Moslemi, Amin Aminian, Reza Masaeli, Behnam Eslami, and Nathaniel S. Treister. 2010. Implant placement in patients with oral bisphosphonate therapy: A case series. Clinical Implant Dentistry and Related Research 12 (3) (09): 175-80.

Shane, Elizabeth, David Burr, Peter R. Ebeling, Bo Abrahamsen, Robert A. Adler, Thomas D. Brown, Angela M. Cheung et al. 2010. Atypical subtroacheteric and diaphyseal femoral fractures: Report of a task force of the American Society for Bone & Mineral Research. Journal of Bone & Mineral Research, e-publication ahead of print, DOI 10.1002/jbmr.253

Shiraki, Masataka, Yasushi Yamazaki, Yumiko Shiraki, Takayuki Hosoi, Naoko Tsugawa, and Toshio Okano. 2010. High level of serum undercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment. Journal of Bone and Mineral Metabolism 28 (5) (09): 578-84.

Silverman, Stuart L., Susan M. Ott, and Richard M. Dell. 2010. Bisphosphonates and atypical femoral fractures. The New England Journal of Medicine 363 (11) (09/09): 1083; author reply 1084-5.

Spence, Michele M., Rita L. Hui, James Chan, and Joanne E. Schottinger. 2010. Risk of skeletal-related events in patients with advanced prostate cancer treated with pamidronate or zoledronic acid. The Annals of Pharmacotherapy 44 (9) (09): 1384-8.

Stagi, Stefano, Laura Masi, Serena Capannini, Rolando Cimaz, Giulia Tonini, Marco Matucci-Cerinic, Maurizio de Martino, and Fernanda Falcini. 2010. Cross-sectional and longitudinal evaluation of bone mass in children and young adults with juvenile idiopathic arthritis: The role of bone mass determinants in a large cohort of patients. The Journal of Rheumatology 37 (9) (09): 1935-43.

Ueda, Takeshi, Yusuke Imamura, Atsushi Komaru, Satoshi Fukasawa, Tomokazu Sazuka, Takahito Suyama, Yukio Naya, Naoki Nihei, Tomohiko Ichikawa, and Masayuki Maruoka. 2010. Treatment outcomes of sorafenib for first line or cytokinerefractory advanced renal cell carcinoma in Japanese patients. International Journal of Urology: Official Journal of the Japanese Urological Association 17 (9) (09): 811-5.

Vallet, Sonia, Matthew R. Smith, and Noopur Raje. 2010. Novel bone-targeted strategies in oncology. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 16 (16) (08/15): 4084-93.

Vasudev, Naveen S., and Janet E. Brown. 2010. Medical management of metastatic bone disease. Current Opinion in Supportive and Palliative Care 4 (3) (09): 189-94.

Venkatanarasimha, Nanda, Gemma Miles, and Priya Suresh. 2010. Subtrochanteric femoral insufficiency fractures related to the use of long-term bisphosphonates: A pictorial review. Emergency Radiology 17 (6) (11): 511-5.

Verron, Elise, Olivier Gauthier, Pascal Janvier, Paul Pilet, Julie Lesoeur, Bruno Bujoli, Jerome Guicheux, and Jean-Michel Bouler. 2010. In vivo bone augmentation in an osteoporotic environment using bisphosphonate-loaded calcium deficient apatite. Biomaterials 31 (30) (10): 7776-84.

Werner de Castro, ,G.R., F. S. Neves, de Magalhães Souza Fialho S.C., I. A. Pereira, G. Ribeiro, and A. F. Zimmermann. 2010. Flare-up of hand osteoarthritis caused by zoledronic acid infusion. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (9) (09): 1617-9.

Won, Emily, Lisa Wise-Milestone, Margarete K. Akens, Shane Burch, Albert J. M. Yee, Brian C. Wilson, and Cari M. Whyne. 2010. Beyond bisphosphonates: Photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue. Breast Cancer Research and Treatment 124 (1) (11): 111-9.

Yamashita, Junro, Laurie K. McCauley, and Catherine Van Poznak. 2010. Updates on osteonecrosis of the jaw. Current Opinion in Supportive and Palliative Care 4 (3) (09): 200-6.

 

Robert G. Edwards : 2010 Nobel Prize Winner in Physiology or Medicine

This year’s Nobel Prize in Physiology or Medicine went to a man whose name is synonymous with “test tube babies” although in point of fact, the equipment that is used for the actual fertilization is more like a petri dish.

Prof. Robert G. Edwards of Cambridge University in England  began his career by systematizing the previous scientific literature on the conditions conducive to the successful fertilization of mammals within laboratory conditions. Then he significantly advanced it experimentally all the way to the human experience.  His research partner, Dr. Patrick Steptoe, (who died in 1988 and therefore could not share in this Nobel Prize with him)  was a well-respected  gynecologist who had experience in gynecological laparoscopic surgery (minor surgery involving the insertion of tubes with lighting and micro-instruments into the gut). He  adapted  existing techniques to the retrieval of human eggs, from ovaries that had been hormonally stimulated to release them in multiples.

Through the combined efforts of Edwards and Steptoe, it finally became possible to combine sperm, which is readily available fresh or frozen (but  which can be thawed on demand), with the ovum, after which the subsequently developing embryo could be frozen for later use,  or be  re-implanted fresh  in the mother, whose uterus would, once again, be hormonally adjusted to be receptive.

Today in Western countries as many as one in 100 live healthy births are the happy result of their pioneering work.

Education and Professional Training

Professor Edwards was in many ways a  clear cut, and almost predictable  British scientific success story. He attended a prominent public high school in Manchester, England (“public” in the American sense, meaning not a private boarding school) that would be very much the equivalent of Boston Latin or Bronx Science in the US. He served honorably in the British Army, and then took a degree in Agriculture at the Bangor campus of the University of Wales (one of the three oldest  and most prestigious of the “red brick” universities in that part of the UK ). He then took his Ph.D. in Animal Science with an emphasis on Reproduction and Genetics at the University of Edinburgh (one of the world’s oldest and most distinguished universities, and the strongest in Scotland in the sciences). He then spent the bulk of his career at Cambridge, arguably the UK’s greatest school in the sciences, and the university home of  88 previous Nobel Prizewinners, more than any other institution on earth.

Succeeding Despite A Lack Of Consistent Scientific & Medical Support In The Early Years

It is perhaps serendipitous that the September 2010 issue of Human Reproduction contains an extensive article documenting the early difficulties of Edwards & Steptoe in gaining reliable financial support for their research (Johnson et al 2010). The stumbling blocks to funding  were not as straightforward  and simple as might be imagined: namely,  opposition from the Roman Catholic Church or religious fundamentalists  to Edwards & Steptoe “playing God”, but rather based on a more complex mix of factors including some practical assessments as to how their research could successfully be carried out without running into snafus based on lack of oversight by the agencies in charge of administering grant monies.  

The Medical Research Council, the UK’s version of the US National Institutes of Health extramural research funding program, basically had four worries, and each had some merit based on what was known at the time.

First, there was an ongoing debate within the MRC leaning towards the idea  that any allocation for  obstetric & gynecological research should focus on the problem of world overpopulation and contraception, rather than on infertility

Second, Edwards and Steptoe felt that they had already gathered enough information from work with other mammals, to proceed  more quickly to humans, while the MRC’s referees felt that they should have extensive trials with chimps first.

Third, Edwards and Steptoe declined an offer to move into a research hospital already being funded and closely supervised by the MRC, since they preferred the greater investigative freedom, the  more genial atmosphere, and apparently, the reduced level of bureaucracy and administrative report-writing  of the University of Cambridge  campus and facilities, even though these were not yet set up for patient care.   The MRC also worried that year-to-year fluctuations in the research  funding of the University might cause disruptions of the university’s portion of the budget for Edwards and Steptoe’s research, since all grants there were competitive and an annual renewal of funds might not be forthcoming if another researcher at the university had come up with a more attractive program.

Fourth,  some MRC administrators apparently felt that Edwards and Steptoe had already gone out of their way to become celebrity scientists through a great deal of media exposure, and should any of the resulting babies be born with birth defects, these researchers  and the MRC as a whole, would not only be easy targets for adverse publicity but possibly also legal action.

However, it proved to be exactly  through the media-savvy  of Edwards and Steptoe that they were eventually able to raise enough private financial support to get their program underway, and after two completely normal births, the MRC reversed itself and funded them generously.

Where Has Edwards Published Most Often? And Would Your Library Have Been Able To Accommodate Him?

Librarians like this blogger often ask themselves if they could have readily fulfilled  the information needs of this Nobel Laureate, using the journals they have selected for their own library’s collections. We keep score of the adequacy of our judgment and budget partly by determining whether the assortment of journals within which this prizewinner published, would be in our holdings, since this test  is one pretty clear surrogate representing a research scientist’s reading needs.

Edwards, it turns out, is typical for most biomedical scientists who attain the Nobel Prize. He has published consistently (over 30 years straight with multiple articles in journals of international importance) and prolifically (over 400 articles) and widely (over 30 different journals, many by invitation), but he also had clear favorites that reported the bulk of his research.

Leading the pack was Human Reproduction, a British-based Oxford University Press journal, which is not only one of the field’s leaders, but which was founded by Edwards in 1986. Along with its companion publication Human Reproduction Update,  it accounted for 81 of his articles.

Edwards was also the founder in the year 2000 of an Elsevier electronic journal that accounted for 42 papers, Reproductive Biomedicine Online.

Three American journals along similar lines also published multiple  Edwards papers. The journal currently called Reproduction (but which until year 2000 was known as the Journal of Reproduction & Fertility, and still published by the Society for Reproduction & Fertility featured 16 papers. Nine Edwards papers appeared in the American Journal of Obstetrics & Gynecology, a collaboration between Elsevier and a coalition of  research and professional groups headed by the American Gynecological & Obstetrics Society. Fertility & Sterility, a journal jointly published by Elsevier and the American Society for Reproductive Medicine,  had eight Edwards papers.

Edwards also had an excellent track record publishing in collateral disciplines. It is no surprise that given the prominent role of hormones in reproduction that he appeared 12 times in the British-based Journal of Endocrinology from the Society for Endocrinology, and given that many of his techniques were based on observing and advancing animal embryology, it is natural that one of the oldest journals with strengths in that field, the Wiley title, the Journal of Experimental Zoology, would be the home for 7 of his articles.

Where Edwards was every bit the Nobel Prizewinner was in his choice of multiscience journals, Nature from Nature Publications Group(25 papers) and  the  Proceedings of the Royal Society of London B – Biological Sciences (7 papers)  and as well as  The Lancet (13 papers),  a leading journal of clinical investigation, from Elsevier. While all three are British-based,  these are among the most influential journals of their type worldwide, and have readerships that are actually greater numerically internationally than in their home country.

How Often Was Edwards Cited And Where Was He Cited?

While counting citations would seem a straightforward exercise in this age of online databases, authors with very common surnames and initials, such as R.G. Edwards,  share that same surname and initials with other scientists. In Edwards’ case there are at least one physicist and another biologist who are also R.G. Edwards, and figures for citations to their papers tend to be commingled and require sorting out. It is nonetheless safe to say that our particular Robert G. Edwards was cited almost 13,000 times in the scientific and clinical literature.

Which journals cited him most often? We ask this because it’s another good proxy measure librarians use in modeling whether or not they could service the needs of a potential patron.

The answers here are not too surprising. According to a sample taken of citations to his most famous papers, we find three journals that consistently account for double digit percentages: Fertility & Sterility, Human Reproduction (both of which were favorite outlets for Edwards) and the Biology of Reproduction ( a US-based journal published by the Society for the Study of Reproduction which tends not to cover human reproduction and as such was not as frequent an outlet for Prof. Edwards).

The next tier is occupied by the journal now known as Reproduction (another Edwards favorite) and by three journals of endocrinology,  the first of which,  the Journal of Endocrinology,  was a preferred venue of Edwards, while  the latter two,   Endocrinology and the Journal of Endocrinology & Clinical Metabolism are  US-based publications of the Endocrine Society.

Rounding out the top ten citers of Edwards are three journals strong in what is now called Developmental Biology, but which was historically termed Embryology.  Edwards had a good track record as both an author and cited authority in the Journal of Experimental Zoology, published a few papers in the journal now known as Molecular Reproduction and Development (originally Gamete Research) a NYC Wiley title that still cites him often, and he is cited frequently by Developmental Biology, a US-based  journal sponsored by the Society for Developmental Biology, and managed by Elsevier.

All in all, the vast majority of works of Robert G. Edwards and citations to those works are concentrated in relatively few scientific and clinical journals (compared to a universe with thousands of titles), and every one of them makes sense to experienced developers of library collections and budgeters for electronic access to journals in the basic life and clinical sciences.

The professional librarians of the BioMedical and Life Sciences Division of the Special Libraries Association had voted no fewer than seven of the journals discussed in this blog posting  to its list of the 100 most influential journals of biology and medicine of the twentieth century (perhaps now better known as the DBIO 100). These include the American Journal of Obstetrics & Gynecology, Developmental Biology, the Journal of Clinical Endocrinology & Metabolism, the Journal of Experimental Zoology,  The Lancet, Nature and the Proceedings of the Royal Society of London B: Biological Sciences. Indeed Nature was voted the Journal of the Centennial of SLA, and the three publishers most often mentioned in this blog posting, Elsevier, Wiley and Nature Publications Group, were ranked first, second and third respectively, in terms of  publishing the most journals within the top 100.

http://units.sla.org/division/dbio/publications/resources/topten.html

Furthermore, a quick check of WorldCat for libraries still having Edwards’ 1,000+ page,  1980 treatise, Conception in the human female, a title described in a review in Nature (Short 1981) as “a treasured possession,” on their shelves shows that it is still likely to be valued in virtually all the major research institutions in not only the US but many in the rest of the world: China, Germany, Israel, Saudi Arabia, and South Africa among them.

 The world has been well served by Professor Edwards and a great many biomedical and life sciences librarians around the could conceivably (pun intended) have returned the favor!

Tony Stankus FSLA [email protected]  Life Sciences Librarian, Science Coordinator & Professor

University of Arkansas Libraries 233E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

Edwards, Robert G. 1980. Conception in the human female. NY: Academic Press.

Johnson, M.H., S.B. Franklin, M. Cottingham,  &  N. Hopwood. 2010. Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971. Human Reproduction 25 (9): 2157-2174.

Short, R.V. 2001. Beyond mechanics in human reproduction. [Review of Conception in the human female by Robert G. Edwards]. Nature 294: 784.

Stankus, Tony & Sarah E. Spiegel. 2009. The SLA DBIO 100 Poll: 100 Journals Voted by SLA’s BioMedical and Life Sciences Division as the Most Influential over the Last 100 Years. Serials Review  35 (4): 202-212.