SLA Biomedical & Life Sciences Division Blog

Is Organized Anthropology Losing Its Senses As It Downplays Its Sciences? Non-Science Areas Might Lose Funding That Comes From Anthropology’s Hard Won but Now Endangered Position as Being one of the “Real” Science Departments on Campus

Anthropology is basically the study of mankind in the past, present and the future. Evolutionary anthropologists would also admit our primate relatives as subjects, and cultural anthropologists would probably go with a definition that included mankind in given societies with particular heritages and customs. The flagship organization for this pursuit is the American Anthropological Association, an organization of about 10,000 academics, museum workers, and expeditionary researchers.

Ordinarily, this is a quiet group that does not much rouse public attention when it engages in internal debates about its mission statement, but in a Tuesday, December 14, 2010, article in the New York Times by Nicholas Wade, it was reported that those in the  organization whose work is science-based were understandably incensed when the word “science” was dropped from the association’s long range planning document, and replaced in some cases with the phrase “the public understanding of humankind.”

What’s going on?

According to the organization, not as much as one would think. In a press release, entitled “AAA responds to Public Controversy Over Science in Anthropology,” http://www.aaanet.org/issues/press/AAA-Responds-to-Public-Controversy-Over-Science-in-Anthropology.cfm these changes “have been taken out of context and blown out of proportion” and “On the contrary, the Executive Board recognizes and endorses the crucial place of the scientific method in much…. [but emphatically not all and maybe not even in the majority anymore of]…. anthropological research.” The association regards anthropology as a “holistic and expansive discipline that covers the full breath of human history and culture…..and draws on the methods of both the humanities and the sciences.”

 

If the reassurances expressed in this press release fairly represent the case, why would scientists in anthropology still be upset? The answer most likely lies in a quote in Wade’s article referencing anthropologists who were aghast at this distancing of the organization from being evidence-based: “How could they [meaning science-based anthropologists at universities where they have to compete with other academic units for funding] justify their department’s existence if their national organization did not regard anthropology as a science?”

 

What I think this means is that many anthropologists whose work involves physical and biological evidence that generates real data based on measurement, who use robust statistics, and develop testable hypotheses do not want to trade being associated with the Biology Department or the School of Medicine for being likened to university departments associated more with performance art, post-modern literary criticism, political activism, social engineering, and assorted gender and race studies. 

This is a real worry because as Dr. Frank Marlowe , President-Elect of the Evolutionary Anthropology Society, an American Anthropological Associate affiliate group, says in Wade’s article: “We evolutionary anthropologists are outnumbered by the new cultural or social anthropologists, many but not all of whom are postmodern, which seems to translate into anti-science.”

This is not to say that university departments which   feature any of these latter non-science approaches are not serious or important to someone.

Recent articles in the flagship publication of the American Anthropological Association, American Anthropologist, and in Current Anthropology, another well respected publication of the University of Chicago Press for the Wenner-Gren Foundation, include studies of torture in South Sudan (Deal 2010),  Palestinian cultural festivals as protests against Israeli occupation (De Cesari 2010),  Intertextuality and Christian ethnotheologies”  (whatever that  means)  (Handman 2010), or the even more cryptic “Clockpunk Anthropology and the Ruins of Modernity (Dawdy 2010).

It’s just that while there may very well now be  a voting majority of the kinds of anthropologists who are interested in, and do the kinds of work represented by titles like this within the membership of the AAA, efforts like these are  probably not as important to major private and governmental agencies (think NSF & NIH, for example)  who are willing to fund  empirical research that will yield  reasonably plausible and provable ----- or at least seriously debatable-----  knowledge about the natural history of our species and its nearest relatives.

And it is the latter group, the funders of scientific research, that have endorsed  the academic respectability and drive the advance of anthropology as much as anyone else.

One of the most curious aspects of the seeming demotion of the science-based anthropologist by the humanities and social-science-based anthropologists is the fact that fields like history, psychology, sociology, and even economics probably benefit as much from science-based anthropological studies as do fields like biology and medicine.

What follows is a small sampler of some recent studies where science can inform humanities and social science scholars and even public policy and gender studies.

A question in the History of Religion: Did early Christians in Roman England value their children more & treat them better than did the pagans?

It is often thought that since some Greeks and Romans basically abandoned babies with birth defects and cast off those young boys lacking military potential, that the introduction of a new religion which preached that at least in some matters, little children should have a place of honor (Matthew 19:14, Mark 10:14) would have greatly improved their lot. However, in a study by Lewis (2010) of burials in graveyards used in the times of the Roman occupation of Britain, the bones of Christian babies and young children (which were buried for religious regions in a east-west alignment) showed vastly more signs of anemia, rickets, and scurvy, than those of pagan babies and young children (which were aligned for religious reasons in a north-south alignment).  The author attributes the adverse outcomes to the practice of early Christians to go so far as to make even infants engage in penitential fasts and their propensity to keep their babies and young children in swaddling clothes for a much longer time than was customary among pagan families (perhaps in the manner of the Baby Jesus in the Gospels (Luke 2:6-7) although the practice was widespread among many different cultures even then).  This longer term swaddling was hypothesized to reduce the Christian child’s exposure to sunshine induced vitamin D production, relative to pagan children who were freed sooner and presumably encouraged to play and exercise outdoors more.

A question in Foreign Affairs & Diplomacy: Is the practice of giving food as foreign aid equally likely to improve the health & nutritional status of the majority of populations living under democratic vs. authoritarian regimes?

While it may seem to be a stretch, there has been a study testing just such a proposition among our primate relatives (Jaeggi, Stevens & Van Scheik 2010). It turns out that the alpha males among chimpanzees held in captivity, despite being particularly fierce hunters of monkeys in the wild,  permit and even encourage food-sharing and other acts of reciprocity among members of their troop, while their closest relatives, the bonobos, despite being a generally matriarchal species who less frequently hunt other primates in the wild, have dominant males who are particularly despotic in captivity, especially around the sharing of food, to the point of sometimes precluding its wider distribution, leading to progressive nutritional impoverishment despite increases in food supply.  Therefore it is not at all improbable that before sending foreign aid in the form of food, it would be wise to determine whether one was dealing with a chimp or bonobo kind of political hierarchy in captivity. (Think Kim-Jong-Il and the question of food aid to North Korea, which goes first and foremost to that country’s massive military and party apparatchiks).

A question in Government, Political Science & Economics: Is the military-industrial complex an entirely new concept or something that has a kind of evolutionary basis in prehistoric weapons production?

There is abundant evidence from strike markings on the bones of humans and large prey animals that Paleolithic men used stone tipped spears to lethal effect.  This is still the case with many indigenous people in remote locations who have not mastered metallurgy and still survive as hunter-gatherers and defend territories or raid the territory of others.  While it may be hard to prove whether or not there was a formal separation of the weapons producers from the weapons users in ancient times, Williams, Gordon & Richmond (2010) have shown through kinematic analysis of the limb and wrist motions of modern day “knappers” (modern day hobbyist makers of stone tools, usually including a fair number of archeologists or anthropologists) that the anatomical mechanics  of making these stone tools expertly  just happen to be the same ones that optimize spear-throwing.  This suggests that it could well be that the original “military-industrial complex” was not differentiated into  manufacturers vs. warriors but rather composed of men who coevolved both to make and use the weapons efficiently, because proficiency in both was essential to survival, particularly in small family groups and tribes which could not spare stay-at-home manpower during hunts or warfare.

A question in Gender Studies: Did women have any health advantages when compared to men in medieval times?

There is little doubt that over the course of history, a great many women died in childbirth while their husbands went on to remarry, and that the maintaining of fires for cooking and heating seemed to have disproportionately left women exposed to the chance of fatal burns, and even that that menstruation and perhaps unfairly shared food supplies left many women chronically anemic and prone to fatal illness. This is apart from fatalities of women visited upon them by their husbands as part of domestic violence or by strangers during wartime rape rampages and pillaging. The question arises: Were there particular times or historical events when being a woman conferred a particular health or survival benefit? The answer would seem to be that only in relatively recent centuries, and even then  seemingly only when the men were at war, have women typically outlived men and this scarcely seems to make up for millennia of their excess morbidity and mortality. However, Sharon DeWitte (2010) has excavated and examined remains in the medieval cemetery in Smithfield, England, that suggest a different outcome during the course of a major epidemic: the Black Plague.  It was pretty clear that there was something operating at least at that time, that made adult men die at a rate almost 50% higher than women.

A question in Psychology: Are there differences in behavioral genetics between indigenous peoples who more quickly become stable and generally law-abiding agriculturalists and those who those who remained significantly longer hunter gatherers living outside the mainstream economic and legal system?

Latin America still possesses significant populations of indigenous peoples who live in locations adjacent to well settled territory but still live by subsistence hunting, fishing, and wild roots and fruits, and have generally resisted attempts to include them into the modern mainstream of agriculture, commerce and law, even as other indigenous peoples in the region  have long adopted agriculture or other occupations and have become well integrated.  While explanations based on cultural beliefs about the sacredness of the land, the enduring value of  being seen as tribes who value bravery in hunting and battle, and taboos about intermarriage or fear of insulting the memory or traditions of their ancestors have all been invoked as explanations, could there be a biological basis that distinguishes those indigenous peoples who have acculturated at some level to modernity and agriculture versus those who, given a choice, would  still wander the jungle or  undeveloped grasslands? The Guarani (whose name comes from the word “warrior” in Spanish, and Kaingang peoples of Central South America (both living primarily in Paraguay and parts of Brazil) were among the last peoples to acculturate in the sense of adopting the agricultural lifestyle assigned them by the colonial Spanish or Portuguese conquerors of their countries, and rarely showed any inclination or success in well-ordered agriculture until the last century,  with the exception of some benign communally run  plantations founded by the Jesuits during the latter 1600s and early 1700s. (It should be noted however, that these same Guarani maintained a particularly fierce home army that, led by Jesuits who were themselves veterans of wars In Europe, was  able to repulse attacks by modern-fire-armed Portuguese slave capturing gangs  numbering in the hundreds to low thousands for decades).  Given that it is now recognized that some genes  contribute to behavioral propensities or special skills, (without necessarily predestining choice of occupation or one’s worldview) Tovo-Rodrigues et al (2010) analyzed the frequency  of dopamine receptor D3 alleles among these two tribes compared to other Amerindian and mixed Amerindian-European populations in Latin America and noted a markedly higher frequency of molecular markers for traits such as novelty-seeking, hyperactivity, and impulsivity, particularly among the Guarani.  It turns out, that these genes and the traits with which they are associated, are extremely common worldwide (and almost predictive) of members of warrior and hunter-gatherer cultures. This is not intended to indicate that these peoples are somehow inferior  to those without these alleles, although it could be appreciated that with them they might not be as adaptable to the sometimes tedious, focused and long-time-commitment demanding nature of modern agriculture, but rather that this genetic endowment  may represent special adaptations to a people who formerly had constantly be on the move, be brave in confronting dangers, and be less predictable to enemy tribes or animal predators who  were seeking to do them harm.

In sum, there is lot that science has to offer to the rest of anthropology, but in short, it is very likely that unless the concerns of science-based anthropologists are surely assuaged the organizational cleft between them and “holistic”, humanities-based anthropologists is going to widen.  It is very likely that the scientists will soon more closely identify with groups like the American Association of Physical Anthropologists, the American Society of Primatologists, the Human Biology Association, as well as organizations in archaeology, biology and medicine that have special interest groups that welcome anthropologists, rather than the American Anthropological Association.

Good riddance, might some cultural anthropologists say!

But the latter may be forgetting that the scientists will take their entrée to funding sources with them as they leave.

Tony Stankus, FSLA, Life Sciences Librarian, Science Coordinator, & Professor

Editor-in-Chief, Science & Technology Libraries

University of Arkansas Libraries MULN 233 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

 

Dawdy, Shannon Lee. 2010. Clockpunk anthropology and the ruins of modernity. Current Anthropology 51 (6): 761-793.

 Deal, Jeffrey L. 2010. Torture by Cieng: Ethical theory meets social practice among the Dinka Agaar of South Sudan. American Anthropologist 112 (4): 563-575.

 DeCesari, Chiara. 2010. Creative Heritage: Palestinian geritage NGOs and defiant acts of government. American Anthropologist 112 (4): 625-637.

 DeWitte, Sharon N. 2010. Sex differentials in frailty in medieval England. American Journal of Physical Anthropology  143: 285-297.

 Handman, Courtney. 2010. Events of translation: Intertextuality and Christian ethnotheologies of change among Guhu-Samane, Papua New Guinea. American Anthropologist  112 (4): 576-588.

 Jaeggi, Adrian V., Jeroen M.G. Stevens & Carel Van Svhaik. 2010. Tolerant food sharing and reciprocity is precluded by despotism among bonobos but not among chimpanzees. American Journal of Physical Anthropology 143: 41-51.

 Lewis, Mary E. 2010. Life  and death in a civitas capital: Metabolic diseases and trauma in the children from late Roman Dorchester, Dorset. American Journal of Physical Anthropology  142: 405-416.

 Tovo-Rodrigues, Luciana, Sidia Callegari-Jacques, M. Petzle-Erler, Luiza Tsuneto, Francisco Solzano, & Mara H. Hutz. 2010. Dopamine receptor D4 allele distribution in Amerindians: A reflection of past behavior differences?  American Journal of Physical Anthropology 143:458-464.

 Wade, Nicholas. 2010. Anthropology group tries to soothe tempers after dropping the word “Science.” New York Times CLX (55,254): A23.

 Williams, E.M., A.D. Gordon & B.G. Richmond. 2010. Upper limb kinematics and the role of the wrist during stone tool production. American Journal of Physical Anthropology 143: 134-145.

When your university’s school of nursing does not have all the resources of a national leader, what’s a defensible, reasonable expectation for the number and kinds of journals which might appear on your CV?

While there are actually many (617) Associate Degree and some (59) Hospital School Diploma programs enabling their graduates to take the NCLEX exam leading to licensure as a Registered Nurse, the clear trend over the last 30 years has been for the bachelor’s degree, granted by one of the nation’s 259 four-year college or university schools or departments of Nursing  to be regarded as the most desirable entry level credential for professional nurses today. 

There are therefore now literally thousands of Nursing faculty at bachelor-degree granting institutions who have faculty status with the possibility of tenure and promotion.

With that status has come increasing pressure for them to publish on a regular basis, much as is required of faculty in other academic department or schools on campus. The problem is that there have traditionally been few rubrics on what constitutes a reasonable expectation in terms of the number of articles and the reputational ranking of the journals within which they might appear.

 

The Old General Rules

 

To a great degree, Nursing had long gotten a pass on some of the stricter norms for scholarly productivity and consideration of the relative prestige of journal venues that one would expect of the Chemistry department in the College of Arts & Sciences, the College of Engineering, or even the School of Medicine, the field closest to it in shared concerns.  This is an unspoken exemption that  at some universities  the School of Nursing  shares  with Schools of Education, Social Work, Home Economics (now better known as Human Environmental Sciences), or even Library & Information Science.

These are all, for better or worse, and mostly for worse in terms of prestige and campus funding, “women’s” service professions  traditionally featuring faculty with  heavy classroom teaching loads and after-class oversight scheduling and coordination duties in sometimes far-flung hospitals and clinics. The terminal degree awarded to their students would typically be a bachelor’s or a master’s degree at best. Course content was simply assumed by higher academic authorities on campus to be based largely on knowledge derived from other more scholarly or higher order professional  fields (i.e. on medicine in the case of Nursing) and that such papers as appeared in the appropriate  journals might best be based merely on years of experience, consensus of practitioners, and fairly simple and typically small-scale empirical work.  

Criteria for what counted as scholarly communication for tenure and promotion purposes was often rather generous (conference talks, poster sessions, book reviews, local or state Nursing newsletter notices) and when articles in journals were considered, it was often enough just to say that they were “Peer-reviewed, “ and let it go at that.

The tenure process generally involved getting the chair of the Nursing Department or School to sign off on the affirmative vote of the already tenured instructors concerning a tenure candidate, and submit this to the Dean, Provost, President or Board of Trustees. The document would somewhere vouch  that the candidate’s publication record in terms of quantity and quality met with the traditions of the Nursing profession as best decided internally by the Nursing faculty themselves.  

Occasionally  a  nominally independent verification of this claim for research sufficiency would be sought from a  small selection of external reviewers. However, these were almost always  from regional peer  Nursing schools selected by members of the local Nursing faculty,  whose reviewers  would frankly be expected to affirm  what the local faculty had to say. Consequently, barring any other independent source of information or advice, the top academic official on campus had little choice or grounds to do anything but sign off on the local faculty vote.

But no more.

The New Order

With time, and as college deans, university provosts, and presidents or chancellors have changed over recent decades, they have been made more and more aware of powerful new online tools that allow them at least some independent bases of comparison of faculty outputs, including those of the departments and colleges of Nursing on their campus with other campuses.

Principal among these are the ability to retrieve online the list of publications in Nursing journals from other institutions (even if could not read the papers with understanding,   these senior academic administrators could certainly count them) and they could even make some reasonably valid use of Thomson-Reuters Journal Citation Reports Impact Factors to see which schools had the highest percentage of articles in journals with the best rankings.

Even if those particular rankings are acknowledged to be imperfect, they are almost always used in the absence of anything else. There is nothing else yet that is  so widely publicized and applied so near universally. (There are for example, over 105 articles in the literature of  my profession, Library & Information Science that involve them in some meaningful way.)

In addition, senior academic officials who evaluate dossiers in scientific and clinical fields have not only developed a pretty good feel over time for which are prominent and reputable publishers, but they can refresh their memories of “who publishes what” with a few mouse clicks without ever leaving their desktops.

Deans, Provosts, Presidents and Chancellors are scarcely alone in adopting and adapting these online finding tools to build up a certain independent level of expertise. They have been joined by people who publish reputational rankings, like the staff of the US News & World Report , and a great many external funding agencies and foundations who wanted to be sure to back winners with their bucks.

To a great degree this new sophistication in discernment of research output  comes at a time when the very newest Nursing faculty members are being judged by the senior members of  departments or schools of Nursing who published little or not at all when they came up, many years ago, and even now  they are uncertain as to how to respond reasonably for verification of the competitive standing of journals, given that many of them still may not be publishing within them frequently.

In short, it can be a confusing time for top academic administrators, senior faculty members of Nursing Schools, and Nurses coming up for tenure or promotion.

The Two Great Questions

 

This confluence of  old  habits and new information  technology has led to the two great questions of the day.

From the Provost or other senior academic officer we get the key credibility question:

“How can I believe your simply saying that a Nursing journal is peer-reviewed,  even with the concurrence of your colleagues at nearby universities that this is so,  conveys  enough information to help me make an informed judgment on your judgment, instead of just rubber stamping it, when I see other programs across the country doing a lot more?”

From the candidate for tenure or promotion we get the key fairness question:

“How can you expect me to publish as many papers and in the same places as  a professor at a top ten school when I have more contact hours, more students, more committees, less internal seed money, no nearby collaborators with research experience, no major teaching hospital or medical school affiliation, no graduate programs here, etc.”

The answers to both questions may provide one very good  solution:

The pattern  of  the national leaders can affirm the basic quality of regional peer output even if the first still numerically overwhelms the second.

A compromise position is actually possible, at least in terms of the journal quality control dilemma, if not in the quotas of articles published. This can be done by comparing the patterns of some of the national leaders against that of regional peers, and looking primarily at the number of schools in either group that publish in the same journals with some frequency. (It’s important that just cherry picking one school out of either group does not allow for good standards setting, because even some nationally prominent schools are eccentric in their emphasis on some journal-----an emphasis that is not shared when other equally prominent schools are added to the mix.)

I first chose ten university-based Nursing schools out of the top twenty from the last US News & World Report ratings (2007), which it must be explained all had  graduate as well as baccalaureate programs, and were based in the same city (and often on the same campus) as their  medical school and their major cooperating  teaching hospitals,  with which they often also offered Advanced Practitioner certification programs.

These programs tended to have larger facilities and faculties than most “ordinary” collegiate Nursing schools, and included endowed chairs in some cases, and major journal editors in all cases. 

These prominent programs  were at universities that generally had national reputations as research leaders in virtually all the fields in which they offered degrees. In short, it was no surprise that these schools were so highly regarded.

I then chose a regional peer group that would be appropriate for much of the Midwest and South, but which pointedly did not include any members of the national top ten group. 

These nursing programs were all accredited and generally based at the flagship or other large campuses of their state university system, but not located within any medical school complex (which typically was located in the largest city or cities in the state away  from the Nursing campus).

While some of these regional peer schools offered graduate degrees in Nursing and Advanced Practice certification programs, others did not.

While some of the programs were parts of identifiably independent Colleges of Nursing nominally co-equal to the College of Education or Arts & Sciences in terms of campus organization and hierarchies, other programs were subsumed into colleges of education or human services or some other cluster of fields.

What best characterized this field was the heterogeneity of the status, size, facilities, staffing,  and enrollment of these schools, a situation which is actually much closer to the reality of the mosaic of collegiate nursing programs today.

Using the Web of Science (WoS) database, I approximated  the 2001-2010 output of Nursing faculty (generally as primary authors)  in what were clearly Nursing journals (as opposed to their coauthored output in journals of medicine, public health, primary or high school health teaching, etc.). I  entered “Nursing”  in a Topic search box, then the  appropriate abbreviation for the school (obtainable from  their clickable online list of approved abbreviations) in an “Address”  search box, and the desired  period from the “Timespan”  boxes. When the results came up, I once again clicked on the “Refine Subject Areas” box for “Nursing”  journals only to keep sharp the focus on Nursing journals alone. I then clicked on the “Refine Source Titles” box to provide “more options/values…” which gave me a most-to-least frequency rank-ordered list of specifically Nursing journals to analyze.

While noting the total journal output for each Nursing program, I decided to focus on comparisons of the more general journals of nursing and nursing education, taking particular note of the top 10 of these for each school,  rather than on parsing out specialty journals such as those devoted more narrowly to cancer,  mental health, or obstetrics nursing, etc.

This was done for  two  reasons:

First, while both groups of schools had both general Nursing journals and some Nursing specialty journals, the types of specialties represented varied greatly, with some specialties absent altogether from regional peer programs making comparisons with national top ten schools problematic.  (On the whole top national top ten Nursing schools featured a higher proportion of its output, up to half, in Nursing specialty journals while regional peers, often lacking access to all the Medical & Nursing specialty services in large teaching hospitals and medical schools, rarely are able to  contribute as high as one third of their output  to similar specialty journals.

Second,   Impact Factor data is  really fair only when all the journals have a similar subject scope (It’s fair to compare one general Nursing journal with another general Nursing journal, but unfair to call, for example, the American Journal of Critical Care a better Nursing journal than the American Journal of Nursing because the two journals  have  significantly different scopes and audiences.)  

So How Did the National Top Ten Do Relative to the Regional Peer Group?

Unsurprisingly, the top ten national leaders published many more articles than the regional peer group: 1415 vs. 614 in the same time frame. What was somewhat unexpected was that while  the top ten general Nursing journals from each group were somewhat different in rank order, they  shared six of the same core titles.

The Six Shared Journals

In alphabetical order we had: the American Journal of Nursing, the Journal of Advanced Nursing,  the Journal of Nursing Education, the Journal of Professional Nursing,  Nursing Outlook, and Nursing Research.

What else do the shared six share?

They are in fact, all refereed.

They are all published by well-known firms and societies.

Wiley has the Journal of Advanced Nursing.

Slack ------well known in Nursing if not in many other fields-------has the Journal of Nursing Education.

Elsevier is represented by Nursing Outlook which it publishes on behalf of the American Academy of Nursing, as well as the Journal of Professional Nursing, issued in cooperation with the American Association of Colleges of Nursing.

Wolters  Kluwer Health, still much better known as Lippincott, Williams & Wilkins, issues Nursing Research in conjunction with the Eastern Nursing Research Society and the Western Institute of Nursing.

Lippincott, Williams & Wilkins also  publishes the American Journal of Nursing, voted by over three quarters of the members of the Biomedical and Life Sciences Division of the Special Libraries Association ------the sponsors of this blog--------- as the single most influential journal of Nursing  of the twentieth century.

How do these six differ among themselves?

Most notably they appear to be all over the map in terms of relative Impact Factors, but this requires some caution before leaping to conclusions.

While two titles, the Journal of Advanced Nursing and  Nursing Research, are clearly among the  most cited general nursing research  venues,  three others are mid-range, Nursing Outlook, the Journal of Nursing Education, and the American Journal of Nursing.

One holds markedly lower rank, the Journal of Professional Nursing, according to the latest JCR rankings to which I have access (2008, the 2009s are out but not yet available to me).  However, even this last title is much better in Impact Factors that might be imagined because the difference in calculations is only a matter of a few tenths of a point between it and the three mid-range journals just mentioned.

 The fact of the matter is that while Impact Factors among Nursing journals give you a good idea of which  five to ten  journals are at the very top or at the very bottom of the approximately 60-70 titles being compared each year , they disclose that almost 40  other Nursing journals are bunched rather closely together, with statistically weak justification for ranking  them in any hard and fast order, other than being in the mainstream,  if not the headwaters or the backwaters of Nursing publications.

What they these Impact Factors nonetheless do is to provide proof that the articles in these journals are cited by other Nursing researchers around the world, at least  to some degree, and are not just local venues of convenience for lesser papers.

What about the journals that are prominent among the top ten national schools but not in the top ten among the regional peers?

There are four journals more prominent among the top ten national programs that do not frequently appear in the top ten lists of the regional peers. (Some authors from the regional peer groups appear in them, but not frequently enough to make the journal one of their top ten titles.)  Which are these, and what can be said about them?

First, all of them are peer-reviewed.

The International Journal of Nursing Studies is published by Elsevier. It is at the very top of general Nursing journals in Impact Factors. It is British-based and has a great many editors from the UK, Canada, Australia and New Zealand in addition to four of whom are senior faculty at US top 10 Nursing programs.

The Journal of Clinical Nursing is published by Wiley. Like the International Journal mentioned above, a journal with which it directly competes,  it is UK based but has an even  broader  representation of editors from the former British Commonwealth the European Union, as well as a few  from notable programs in the US. It is not quite at the top, but in the top quarter in terms of Impact Factors.

The Journal of Nursing Scholarship is published by Wiley on behalf of Sigma Theta Tau,  the US national Nursing honors society. It ranks in the middle of the field in Impact Factors.

The Western Journal of Nursing Research is published by Sage Press, a notable firm in the Social Sciences and Education, on behalf of the Midwestern Nursing Research Society. It ranks in the middle of the field in Impact Factors.

In sum, all four are very sound journals at the top or mid-range of Nursing in prestige and Impact factors. Two are clearly more cosmopolitan in authorship and readership than most titles favored by our regional peer group faculty.     

What about the journals that are prominent among the  regional peer schools but not in the top ten among the national top ten schools?

There are four journals more prominent among the regional peer programs that do not frequently appear in the top ten lists of the national top ten schools. (Some authors from the top ten schools appear in them, but not frequently enough to make the journal  one of their top ten titles.)  Which are these, and what can be said about them?

Two of these journals are theme-issue based, meaning that the journal editor or a guest editor assembles a panel of expert authors on a single topic on which each article focuses. Publishers are fans of this journal format, because it frequently generates extra sales of  individual issues as a kind of topical best practices collection, or state of the art review. It is clear that some editing of submitted manuscripts must be involved but it seems that the crucial point in quality control, may not be traditional double blind peer review, but rather getting the issue theme and its author team approved fairly early on in the process.

It is not surprising that the two journals involved, Nursing Clinics of North America and Advances in Nursing Science are direct competitors. Nursing Clinics comes from Elsevier, while Advances is a Lippincott, Williams and Wilkins title. Nursing Clinics fares rather poorly in Impact Factors while the Advances are in the top quarter by that measure.

The two other titles where regional peers appear quite often are Nursing Education Perspectives from the National League of Nursing, and Nurse Educator from Lippincott, Williams & Wilkins. Both are peer-reviewed in the more traditional sense,  but both titles fares poorly in Impact Factors.

Does the presence of these regional peer four titles tell us much vis-à-vis the four titles of the top ten schools?

I think it is safe to say that overall, the higher level of research  may be found in the top ten school four than the regional peer four, but that the regional peer four titles make more sense for Nursing professors who still view their jobs primarily as teachers.  Two of their titles are clearly focused on methods and trends in teaching Nursing, while the remaining two provide in effect, high-level course packs quite literally authored by teams of invited experts for upper division and graduate courses.

What is the consensus opinion of medical librarians on this?

The closest thing that my profession has to say on this, apart from voting the American Journal of Nursing the most influential of the 20^th century,  comes from a continuation of the old Brandon-Hill List, published and republished in a number of places, but most pertinently for our purposes in Nursing Outlook 2002; 50:100-113. It names the following journals discussed in this blog as essential to any Nursing collection: Advances in Nursing Science, American Journal of Nursing, Journal of Nursing Education, Journal of Nursing Scholarship, Journal of Professional Nursing, Nursing Clinics of North America, Nursing Education Perspectives, Nursing Outlook, and Nursing Research. It considers the following to be genuinely reputable, sound journals  that would be good additions to any Nursing collections, after the essentials were already in place: Journal of Advanced Nursing, Nurse Educator,  and the Western Journal of Nursing Research.

 I suspect that the marginally lower rating given to the Journal of Advanced Nursing, might provide us with an explanation of why the International Journal of Nursing Studies and the Journal of Clinical Nursing were not included: the list is slanted to stocking the small US hospital library  and favored journals that had a higher proportion of American research or researchers, and was not necessarily a reflection on their quality as venues for scholarly work on the whole.

Indeed, the biggest surprise for those who are too ardent in using Impact Factors without considering other factors, is that one title identified by two expert librarians as essential, the Nursing Clinics of North America,  is ranked so poorly, while the people who most closely monitor journal use in terms of what circulates or is read-online, the remaining community of medical librarians, are very likely to second Brandon-Hill’s high regard for it.

Advice to provosts and nursing faculty seeking tenure & promotion, neither of whom are not at a top ten university school of nursing .

Regional Peer School Provosts, if your candidates manages to publish about half as many papers as their peers in a top ten school, they are probably doing quite well with the resources you are able to provide them. You are going to have to give them more to get more out of them. Impact factors are one tool for you to use, but not the only tool in making your evaluation. Do  not expect all of their  papers, now and even in the future,  to appear in journals ranking in the top quarter in Impact Factors.  But by the same token  be very leery of an assortment of papers in which few if any come from that Impact Factor level, particularly if there are no top ten school authors in the journals in which your own faculty publish  for prolonged stretches of time. (If no top ten schools publish in a journal over the course of a year, be suspicious and ask for explanations.) Look for the usual  statements of peer-review and rely on the reputation and longevity of the publishers behind the journal. They did not get to be “venerable robber barons”  by selling their principal buyers (medical librarians, as it turns out) unadulterated tripe. They have built their demand by being in their own way very demanding of their editors and authors.

Nursing Faculty Members At Regional Peer Schools: Choose more wisely than ever the journals within which you send your manuscripts. Getting at least some of your papers into some of the shared six titles in this paper, is probably a very good idea, both because it is routinely done by the very talented, very driven, very hard-working scholars in top ten schools ------and because it has demonstrably been done by your regional peers at least some of the time. Do not, however, be ashamed of being primarily a Nurse educator. You may well not have as much ready access to specialty research teams at a medical school or its teaching hospital and few if any of your colleagues are likely to be major Nursing journal editors, but you do have at least as much access (and probably much more contact time) as well as a great responsibility to the kids in front of you and the patients that will one day be in their charge. Studies involving understanding their pre-Nursing  backgrounds and abilities, improving their understanding of Nursing concepts and procedures, and the monitoring of their follow-on careers and needs for continuing education, remain important to both your career and to the profession at  large. Nonetheless, when the opportunity presents itself, to do work that leads to publication in Nursing specialty journals, jump on it. It will be a good way to distinguish yourself and promote diversity of expertise in your own Nursing school or department.

 

 

 

 

 

 

 

 

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.

Genetically Modified "GM" Salmon Raised In Self-Contained Systems: Much More Likely To Be Part of a Solution and Not a Problem

A New York Times article (Pollack 2010) appeared on Tuesday, September 21, 2010,   and discussed whether or not specially genetically engineered farmed salmon might be approved for sale in the US. There were representatives of the aquaculture industry and of the firm pushing the idea, AquaBounty  Technologies, speaking in support before an FDA panel, and a number of special environmentalist or consumer’s groups going on record as against the idea in general, or some particular aspect that they felt was underexplored or held potential danger. 

The critics brought up a number of issues that  were treated as being so important of themselves, that the approval process should be delayed or cancelled altogether. But such a single-issue-based disapproval  sometimes overlooked other factors and realities of  salmon ecology,  economics,  and even human medicine, when a more holistic and  interdisciplinary view of the risks and benefits of this AquAdvanatge™  salmon and its method of being aquacultured might be more revealing.

What’s the big deal with salmon?

Salmon now leads in US sales of all fresh, refrigerator case finfish in supermarkets and is the third most consumed seafood product just behind frozen shrimp and canned tuna (National Fisheries Institute 2009). It’s considered to be particularly good for you. It is nationally promoted, responsibly endorsed,  and widely perceived as having health benefits, especially its polyunsaturated fats and omega-3 fatty acid content (Harel et al 2001, Horrocks & Yeo 1999) that outweigh  its risks from mercury for most categories of consumers (Foran et al 2005, Smith & Guentzel 2010). Demand is expected to grow in the restaurant and institutional food service trade not the least because salmon is one of the most popular types of sushi and sashimi  among both high school (FoodServiceDirector 2010) and college age  consumers (Boss 2009).

Why do they farm salmon anyway? Can’t we just catch more wild salmon in the ocean?

Atlantic salmon are still caught in the wild, but their reproductive carrying capacity has long ago been reached, and Atlantic salmon fisheries have basically harvested (and often polluted) themselves out of business in many locales, including most of New England, formerly a rich salmon fishing area. Indeed most wild Atlantic salmon served in the US has been imported from Canada, the UK, or Scandinavian countries, but even so, catches have been declining: In 1996 we imported 566 tons of wild caught salmon, but by 2008 that amount was down to 58 tons.

It should be noted that while the Alaskan wild salmon fishery ----involving a number of different salmon species but not the Atlantic salmon----remains reasonably healthy, the other West coast native salmon fisheries running from Northern California through to British Columbia, have been in severe decline owing to overfishing and environmental calamities, and thus will not provide a ready, sustainable alternative in the future (US Fish & Wildlife Service 2010). The only realistic  alternative source for a growing demand for salmon is to use aquacultured salmon.

Can’t we just stock the rivers with more salmon from salmon hatcheries, and let them grow up in the wild in the ocean and have them return to the rivers where we stocked them, just like wild salmon do?

This is being done in Alaska and Northern Europe with some success (and in the Great Lakes although the population cannot reproduce there)  but there are still problems: The stocked fish generally behave like escaped farmed fish and sometimes out-compete the wild fish, and it is not always clear that wild and stocked fish interbreed  successfully, even though they are of the same species. This means that it is sometimes possible to end up, not with an overall increase in the total number of available salmon, but rather the displacement of one type of salmon by another without any net gain in salmon supply.  (Crozier 1993, Erkinaro et al 2010, Skaala,  Glover &  V. Wennevik  2006, Soto, Jara & Moreno 2006,  Uusitalo, Kuikka & Romakkaniemi 2005).

 

 Why do they want to genetically engineer a naturally perfectly good fish in the first place?

The principal reason is that these fish, when farmed, grow to harvest size in about half the time as non-genetically-engineered farm-raised salmon, and that this quick turnaround time means that they can be economically grown in closed aquatic systems, meaning not in pens in the open ocean or nearby brackish waters, but rather in clean artificial ponds  much like modern American catfish farming, ponds or tanks which do not connect to rivers or the ocean. As seen in the catfish farming industry (Stankus 2010), many more variables regarding fish wholesomeness and taste,  water quality, the presence of parasites and diseases, the management of waste products, are much more controllable, although realistically never perfectly controllable, in such closed systems. Salmon farming in a closed system represents a serious incremental improvement in the food safety, economics and as we will see shortly, in the environmental impact of salmon aquaculture.  Genetically modified salmon raised in closed systems will go a long way to exploding the simplistic folkloric natural foods ideology  that Norwegian fisheries researcher  Oivind Bergh (2007) calls the dual myth: That wild fish are always healthier (and therefore always better for you) and that farmed fish are always unhealthy (and therefore always worse for you).  

How do these genetically modified salmon grow so fast?

Basically, two genes have been inserted into their genomes. One gene simply enables internal growth hormone production year round despite the cold (salmon ordinarily stop making growth hormone in cold weather and therefore stop growing during winter months). The second gene basically enables the first gene to activate and do its work.

Most importantly, no hormones that are not native to fish are introduced to this  fish, nor are they fed hormones in their rations. There is no reasonable scientific basis for suggesting that these fish are somehow hormonally disruptive of humans or other animals that might eat them, or even that the enhanced growth hormone production, is damaging to the fish themselves, the arguments used against hormones given to livestock and dairy cows through feed or direct injection.

Why can’t we just wait for the traditional growing out period of non-genetically engineered salmon farmed in bays and estuaries?

There are at least three reasons that make quicker growing farmed salmon, grown in closed systems, a better idea than farmed non-genetically modified  salmon raised in sea pens.

The first is ironically ecological or environmental: Salmon farmed in the traditional manner in pens in bays and estuaries tend to become infested with sea lice, which, while not known to be harmful to humans, stunt the growth and well-being of the salmon being farmed. Unfortunately, once the sea lice find themselves a fertile home base, such as the trapped farmed salmon, they spread, not only to nearby wild salmon, but to other fish species as well, sometimes decimating their number(Costello 2009, Frazer 2009).

The second is also ecological and environmental: The sea floor beneath and areas surrounding sea pens are typically fouled with fecal products, uneaten food, and trace chemicals used to keep the cages from becoming coated with barnacles,  weeds, and the like. Perversely, the increased organic matter in the waters near the cages actually decreases the oxygen levels in the water as well as  the number of toxic compounds in the immediate area by binding with agents that would otherwise remain in solution and generally in a diluted state (Musclow 2005, Mayor et al 2010). See the following for more details.

The third reason is also environmental but includes some clinical implications as well: Quicker growing fish raised in closed aquatic systems with closely monitored water quality show demonstrably lower rates of bioaccumulation of environmental toxins including heavy metals, runoff fertilizer compounds, and especially trace pharmaceuticals like antibiotics used to suppress assorted bacterial and fungal infections in salmon penned up in bays and estuaries (Burridge 2010, Cabello 2006, Fortt, Cabello & Buschman  2007). These materials are not only generally bad for the sea life around them, but, should they accumulate within human consumers, poisonous and potential enablers of diminished antibiotic effectiveness, as they encourage the proliferation of drug resistant bacteria in the environment (Herwig, Gray & Weston 1997).  

What will happen to wild salmon if these genetically engineered fish somehow escape their closed systems and mate with natural salmon populations?

First, at least as currently planned in terms of their major sites of production, the salmon will be raised in places where even the nearest sea and river waterways are seriously unfavorable to them, so it is likely that they would die out because they were in such unsupportable circumstances.

Second, all of these fish are females,  and by design, about  five out of every six are demonstrably sterile. Such a sex ratio and high rate of infertility does not bode well for them to be able to establish a viable invasive population which can compete with local, native fish. (Which generally do not include members of the salmonid family with which they could conceivably try to mate.)

What about possible allergic reactions?

It is unfortunately true that there are a great many people allergic, and sometimes severely so, to proteins in seafood, including proteins in Atlantic salmon (Pitsios et al 2010). However, there is as yet no evidence that the two genes that have been inserted into these AquaAdvantage Atlantic salmon will cause the production of any proteins that are not already likely to be in any other type of Atlantic salmon. A safe and sensible recommendation  would be for people who are known to be allergic to Atlantic salmon not to eat any Atlantic salmon, AquAdvantage type or not, and for the rest of us to eat available Atlantic salmon including AquAdvantage salmon when we want to, because we like it and it is a generally healthy food.

Shouldn’t there be warning labels on such salmon?

Given that there are no known differences in the food safety or nutritional value of these salmon, there is no scientific justification for putting any kind of warning label on them. It might be fair to consumers who, for whatever reason, prefer wild-caught salmon or farmed salmon, to have the salmon labeled simply as wild-caught or farm raised salmon, and mention the country of origin.  This is pretty much the standard procedure in most supermarkets anyway, and as noted below, seems to have little effect on sales. People buy what looks good to them at the lowest price they can get.

Are there any foreseeable disadvantages to genetically modified salmon of this type raised by this method?

Overexpectation, too much “hype” in terms of  certain ecological and economic impacts  is about the only forseeable problem.

At least three pre-existing dilemmas will likely persist despite the adoption of this genetically modified salmon and its method of being raised, but these dilemmas  would also continue without them.

1. Detrimental impact on the global population of small fish and supply of fish byproducts. While all the science thus far suggests that with proper care, these fish can be raised safely within closed systems with virtually no risk to the local fish population by direct invasion of their waterways  and competition for food within them, problems remain with the need of all carnivorous fish (and this includes salmon, farmed or wild) for smaller forage fish, usually caught in the wild to be turned into fish meal for the pellets fed to the salmon, and this can cause population declines in fish that would feed other fish in the wild or feed humans (think anchovies and sardines, for example) directly (Aubin et al 2009, Ayer et al 2009, Mullon et al 2009, Pelletier et al 2009).

 

2. This new type of salmon and way of producing it will not likely produce a great many more jobs in the poorer countries that host these or any other modern aquaculture operations. Unemployment in the poorer countries where this type of aquacultured salmon (and any other type of aquacultured salmon) will not dramatically decrease, because operations such as these are  much efficient in their  use of manpower, particularly when compared to  the still large numbers of increasingly impoverished local traditional fisherfolk attempting to land ever diminishing catches.  This is not to say that the fewer workers in modern farmed fishing would not, in the long run, be better off, particularly if there was a requirement that these international aquaculture companies hire and train displaced local fisherfolk, instead of bringing in alien crews for permanent operations  (Adeel & Safriel 2008, Grigorakis et al 2010 ).

 

3. This new type of salmon and way of producing it will not likely increase the availability of low-cost, high-quality protein in the poorer countries that host these and any other modern aquaculture operations. Barring “set-aside-some for domestic use”  legislation in the countries in which these operations are set up, the local population will  probably not have greatly increased access to cheap salmon for their own consumption. The overwhelming share of farmed (and wild caught) salmon is sold on the international market as a cash crop to wealthy, highly developed countries like the US, and their consumers tend to buy the lowest priced salmon of comparable quality and freshness, regardless of which country was the source (Wozniak 2010).

 

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

University of Arkansas Libraries MULN 233 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Fax: 479-575-4592

Voice: 479-409-0021

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Frazer, L. Neil. 2009. Sea-cage aquaculture, sea lice, and declines of wild fish. Conservation Biology 23 (3) (JUN): 599-607.

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Mayor, Daniel J., Alain F. Zuur, Martin Solan, Graeme I. Paton, and Ken Killham. 2010. Factors affecting benthic impacts at Scottish fish farms. Environmental Science & Technology 44 (6) (MAR 15): 2079-84.

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Mullon, C., J-F Mittaine, O. Thebaud, G. Peron, G. Merino, and M. Barange. 2009. Modeling the global fishmeal and fish oil markets. Natural Resource Modeling 22 (4) (NOV): 564-609.

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Tuberculosis, TB, is on the Rise Again

If there was a celebrity cause of death of the last millennium, it was probably tuberculosis. According to an unsigned, but rather exhaustive inventory,  matter-of-factly entitled "List of tuberculosis victims" http://en.wikipedia.org/wiki/List_of_tuberculosis_victims, which I fact-checked for  two dozen or so names,  it does seem likely that all of the following died of TB or its complications: John Calvin, Cardinal & Regent of France Richelieu,  Saint Theresa and Saint Bernadette Soubirous of Lourdes, all of the Bronte sisters, Elizabeth Barrett Browning, John Keats, Eugene O’Neill, William Somerset Maugham, D.H. Lawrence, George Orwell, Alexander Pope, Washington Irving, Moliere, Sir Walter Scott, Laurence Sterne, Henry David Thoreau, Robert Louis Stevenson, Jean-Jacques Rousseau, Frederic Chopin, Igor Stravinsky, Anton Chekhov, Maxim Gorky, Simon Bolivar, President James Monroe, Eleanor Roosevelt, Alexander Graham Bell, Louis Braille,  Immanuel Kant, Florence Nightingale, Baruch Spinoza, Ho Chin Mihn & W.C. Fields. But TB is scarcely a “dead disease. ”  Every year over 9,000,000 new cases are reported and 2,000,000 die from it. (Das & Horton 2010, Lonnroth et al. 2010). This is in contrast to the numbers who died during the recent, much more highly publicized H1N1 misnamed “swine flu and/or bird flu” epidemic: 14,286, according to the European Centers for Disease Control & Prevention.

 

Who Gets TB Today?

 

While anyone can conceivably get TB today,  the following are among the most likely victims today. Poor urban dwellers (Cantwell et al 1998) with a history of alcoholism (see, for example Mathew et al 2010) and smoking (see for example  Silva et al 2010)……although neither poverty nor alcohol nor tobacco use cause TB of themselves). Recent immigrants to developed Western countries from underdeveloped countries in Africa, the Middle East & Central Asia, or South East Asia (see for example Buu et al 2010, Menzies et al 2010), where TB is much more common. Certain isolated indigenous peoples, including some Native American Indian tribes (Breault & Hoffman 1997) .  Dairy herdsmen and slaughterhouse workers, veterinarians,  doctors, nurses, dentists (see for example Cadmus et al 2010) workers and the very people who fight TB the most: Public Health workers (Hanscheid & Grobusch 2010, Jong Lee et al 2010,  Ling & Menzies 2010). And just about anyone with HIV, particularly in Sub-Saharan Africa. TB hits children (Marais & Schaff 2010)  and the elderly (Mori & Leung 2010) much harder than adults.

 

From What, Where or Whom Do They Get TB?

 

Well over 90% of TB is transmitted from person-to-person. In other words if you have been exposed to people who are in their active stage of  TB, people whose  levels of Mycobacteria tuberculosis bacteria are such that they are abundant in their sputum which is sprayed about mostly through coughing and sneezing, long enough or in the right close circumstances, you can contract TB. Single digit percentages of TB are contracted from animals or animal products: most commonly through consuming unpasteurized dairy products and occasionally red meat. The causative agent is Mycobacterium bovis (so-called bovine or zoonotic TB).  (Chickens can get their own form of TB, but transmission of that type to humans is not common, although chickens can give it to cows, where it causes Johne’s Disease).  

 

However, TB is an equal opportunity disease: people can get it from their relatives, their cows, dairy products, and even from wildlife, and can give it right back to the sources they got it from or their uninfected  herd or pack mates (Rock et al 2009)! Humans can infect cattle, whose excreta infects wildlife (in the US mostly deer, in the UK mostly badgers, in Africa wild buffalos and wildebeest, and anything that eat the wildlife or the cattle,   so that wolves, lynxes, lions can get it and give it back too through saliva and excreta.) Humans can transmit the bovine form just as well as they can the more common M. tuberculosis form to other humans or to animals, and animals can give humans either type as well. Indeed, the best theory of TB origins have it arising from mutations of very tough soil-born versions which became capable of infecting  livestock which in turn infected herdsmen.  North Africa, Europe and Asia seemed to have developed both human and bovine types before the disease spread to Australia or the Americas. Indeed, traces of TB have been found in wooly mammoth and ancient musk oxen and bison  frozen remains and bones on both sides of the Bering Strait, with a trail running down through the west coast of the US (Rothschild & Martin 2006).

 

Given that TB seems so infectious, why don’t more people have it?

 

The short answer in the western world of North America and most of Europe, is that more people used to have it, but three developments halted its more rapid spread, and knocked down its numbers dramatically.  First, TB patients were very often quarantined in sanatoriums, cutting down on further person-to-person transmission, although health care workers at those facilities even now have elevated chances.  Second, dairy products overwhelmingly  became sold to the public only after pasteurization – a heating process which kills the bacteria. Cows that tested positive for TB in their milk were often put down or successfully treated with antibiotics until the infection cleared and even the antibiotics that cured them also cleared from appearance in the milk. Third, a number of drugs were developed that knocked down or completely eliminated the Mycobacteria in both humans and livestock. A fourth factor is now clear: some people and animals have an unusual genetic propensity for resisting the disease, while others have heightened genetic susceptibility (Allen et al 2010).

 

Can’t people be easily diagnosed, take their medicines, and get cured?

 

The diagnosis of TB is usual done by a tuberculin skin text (the PPD) and/or chest x-rays. While the PPD is still usually quite reliable, it does give out a small number of false negatives and false positives. One reason for the false positive, is that foreign-born patients may have received doses of BCG vaccine, which triggers this result. These vaccines are commonly used in an attempt to prevent TB in Europe, Africa and parts of Asia, but owing to limited effectiveness, are  rarely used in the US.  Chest x-rays however, seem to be even less useful on close examination than were previously thought (Eisenberg & Pollock 2010), although they are still frequently required as a condition of employment, of  attending college, or joining the military, a practice going back to the times of WWII. More sophisticated tests are constantly being developed, but most are  more expensive and less widely distributed than  their predecessors (see for example Chen et al 2010, Graham 2010,  Idh et al 2010).

 

The real problem with medications is two-fold: Many patients are non-compliant because the course of drug treatment can be months long, and they start feeling better sooner than the mycobacteria are totally eliminated. Patients with the quiescent “latent” form of TB often have no symptoms at all, and only know that they have TB owing to a PPD test, and resent having being forced to take medications, particularly after they are reassured that they are unlikely to be able to give anyone else TB while the disease is in its latent stage……the problem is that a number of other medical crises can precipitate the development of active TB disease, and that they become quite infectious to others and very sick themselves.   While many governments subsidize the cost of these medications, they are  not always free. Furthermore, in western societies, many immigrants of uncertain legality are leery about complying with  government agencies for fear that they will be deported (see for example Kulane, Ahlberg & Berggren 2010).

 

Perhaps an even larger problem is the development of resistance to standard drugs of choice like Isoniazid (INH) and Rifampin (RIF) and a few other analogues that have served us well for several generations. Multiple Drug Resistance (MDR -----resistant to two standard drug types ) and Extensive Drug Resistance (XDR ----- resistant to all four standard drug types) are becoming a problem for hundreds of thousands (Dheda et al 2010, Hasan et al 2010,  Metcalfe et al 2010). Most of these patients will either become stabilized for short periods of time on ever more exotic combinations of drugs taken on a trial basis,  with the hope that their disease reverts to latency. But many more will die.

 

What can be done now?

 

• Immigrants from countries where TB is endemic need to be screened using more sophisticated tests such as the QuantiFERON®-TB Gold (QFT-G), QuantiFERON®-TB Gold In-Tube test (QFT-GIT); and T-Spot®.TB test. They are only moderately more expensive and show good results (Idh et al 2010). These test must be  administered with scrupulous oversight and integrity of recordkeeping in settings that include modern instrumentation (Nkengasong et al 2010). Patients who test positive should be thoroughly treated before being allowed to immigrate. The developed world to which these unfortunate people wish to move must underwrite the higher cost of better diagnosis and treatment as being in its own enlightened self-interest.

 

• As suggested by practical trials in places like Taiwan (Tsai et al 2010), paying patients financial incentives for compliance with long term drug treatments for latent TB may be more effective and cheaper than police pursuit or treating full-blown TB cases that emerge from untreated latent TB.

 

• Drug research into new anti-TB agents must continue apace. (see for example Patel, Khani & Rajani 2010).

 

• Research into treatments for AIDS is in many cases also preventive or concurrent for  dealing with TB, so that advances in one almost always aid the other (Pathak, Wentzel-Larsen & Asju 2010, VanZyl-Smit et al 2010.

 

• Continued vigilance concerning  Mycobacterium bovis in farm animals, farm products and wildlife, is a relatively low-cost means of holding down  to about 60,000 deaths annually this form of TB. Providing the means for  immunizing and treating animals and/or absolute guarantees of compensation for putting down  infected animals are at this time the best that can be done, and barring a foolish abandonment of pasteurization and a generalized return to raw milk products, likely to succeed (see for example Wee et all 2010) and perhaps even reduce those numbers. For an exhaustive overview of this story see the forthcoming Hardin, Crandall & Stankus (2010).

 

• Fundamental research into the cooption of the host  immune system and the drug resistance bacterial genetics of Mycobacteria will likely give us the best long term outcome, while we fight on public health and pharmacological fronts for now (Behar, Devangai & Remold 2010).

 

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: 470-409-0021

Fax: 479-575-4592

 

Allan, K. M., E. Murphy, and J. G. Ayres. 2010. Assessment of respiratory health surveillance for laboratory animal workers. Occupational Medicine (Oxford, England) 60 (6) (09): 458-63.

 

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Behar, Samuel M., Maziar Divangahi, and Heinz G. Remold. 2010. Evasion of innate immunity by Mycobacterium tuberculosis: Is death an exit strategy? Nature Reviews.Microbiology 8 (9) (09): 668-74.

 

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Cadmus, Simeon I., Victoria N. Okoje, Babafemi O. Taiwo, and Dick van Soolingen. 2010. Exposure of dentists to Mycobacterium tuberculosis, Ibadan, Nigeria. Emerging Infectious Diseases 16 (9) (09): 1479-81.

 

Cantwell, M F, M T McKenna, E McCray, and I M Onorato. 1998. Tuberculosis and race/ethnicity in the United States: Impact of socioeconomic status. American Journal Of Respiratory And Critical Care Medicine 157 ( 4 Pt 1) : 1016-1020.

 

Chen, Ru, Yingzuo Bi, Guohai Yang, Zhiling Liu, Zhihui Liu, Bijian Zeng, and Tiezhu Tong. 2010. Development of a fluorescent microsphere-based multiplex assay for simultaneous rapid detection of mycobacterium tuberculosis complex and differentiation of M. tuberculosis and M. bovis in clinical samples. Diagnostic Molecular Pathology: The American Journal of Surgical Pathology, Part B 19 (3) (09): 172-9.

 

Das, P., and R. Horton.  2010.  Tuberculosis-time to accelerate progress.  The Lancet 375 (9728):  1755-1756.

de Klerk, Lin-Mari, Anita L. Michel, Roy G. Bengis, Nicolaas P. J. Kriek, and Jacques Godfroid. 2010. BCG vaccination failed to protect yearling African buffaloes (Syncerus caffer) against experimental intratonsilar challenge with Mycobacterium bovis. Veterinary Immunology and Immunopathology 137 (1-2) (09/15): 84-92.

 

De Schutter, Iris, Kinda Schepers, Mahavir Singh, Françoise Mascart, and Anne Malfroot. 2010. Latent tuberculosis in a newborn: Diagnostic challenges. European Journal of Pediatrics 169 (9) (09): 1155-8.

 

Dheda, Keertan, Robin M. Warren, Alimuddin Zumla, and Martin P. Grobusch. 2010. Extensively drug-resistant tuberculosis: Epidemiology and management challenges. Infectious Disease Clinics of North America 24 (3) (09): 705-25.

 

Eisenberg, Ronald L., and Nira R. Pollock. 2010. Low yield of chest radiography in a large tuberculosis screening program. Radiology 256 (3) (09): 998-1004.

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Hänscheid, Thomas, and Martin Peter Grobusch. 2010. Biosafety and tuberculosis laboratories in Africa. The Lancet Infectious Diseases 10 (9) (09): 582-3.

 

Hardin, Amy, Philip Crandall & Tony Stankus. 2010. The zoonotic tuberculosis syndemic:  A literature review & analysis of the scientific journals covering a multidisciplinary field that includes clinical medicine, animal science, wildlife management, bacterial evolution & food safety. Science & Technology Libraries, 29 (4): in press.

 

Hasan, Rumina, Kauser Jabeen, Asho Ali, Yasraba Rafiq, Rabia Laiq, Babar Malik, Mahnaz Tanveer, et al. 2010. Extensively drug-resistant tuberculosis, Pakistan. Emerging Infectious Diseases 16 (9) (09): 1473-5.

 

Idh, Jonna, Ebba Abate, Anna Westman, Daniel Elias, Helena Janols, Aschalew Gelaw, Assefa Getachew, et al. 2010. Kinetics of the QuantiFERON((R))-TB gold in-tube test during treatment of patients with sputum smear-positive tuberculosis in relation to initial TST result and severity of disease. Scandinavian Journal of Infectious Diseases 42 (9) (09): 650-7.

 

Jong Lee, Kyung, Young Ae Kang, Young Mi Kim, Sang-Nae Cho, Jin Wook Moon, Moo Suk Park, Se Kyu Kim, Joon Chang, and Young Sam Kim. 2010. Screening for latent tuberculosis infection in South Korean healthcare workers using a tuberculin skin test and whole blood interferon-gamma assay. Scandinavian Journal of Infectious Diseases 42 (9) (09): 672-8.

 

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Kulane, Asli, Beth M. Ahlberg, and Ingela Berggren. 2010. "It is more than the issue of taking tablets": The interplay between migration policies and TB control in Sweden. Health Policy (Amsterdam, Netherlands) 97 (1) (09): 26-31.

 

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Maragou, Chrysoula, Nadia Theologie-Lygidakis, Panayotis Ioannidis, Antonia Stenou, Sophia Kanavaki, Ioannis Iatrou, and Maria N. Tsolia. 2010. Primary tooth abscess caused by Mycobacterium bovis in an immunocompetent child. European Journal of Pediatrics 169 (9) (09): 1143-5.

 

 

Mathew, Trini A, Alan L Shields, Aizhan Imasheva, Sonya S Shin, Sergey P Mishustin, Gennady G Peremitin, Aivar K Strelis, Galina V Yanova, Shelly F Greenfield, and Jennifer J Furin. 2009. Knowledge, attitudes, and practices of physicians in Tomsk Oblast tuberculosis services regarding alcohol use among tuberculosis patients in Tomsk, Russia. Culture, Medicine And Psychiatry 33 (4): 523-537.

 

Marais, Ben J., and H. S. Schaaf. 2010. Childhood tuberculosis: An emerging and previously neglected problem. Infectious Disease Clinics of North America 24 (3) (09): 727-49.

 

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Metcalfe, John Z., Elizabeth Y. Kim, Grace Lin S.Y., Adithya Cattamanchi, Peter Oh, Jennifer Flood, Philip C. Hopewell, and Midori Kato-Maeda. 2010. Determinants of multidrug-resistant tuberculosis clusters, California, USA, 2004-2007. Emerging Infectious Diseases 16 (9) (09): 1403-9.

 

Mori, Toru, and Chi Chiu Leung. 2010. Tuberculosis in the global aging population. Infectious Disease Clinics of North America 24 (3) (09): 751-68.

 

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Patel, Navin B., Imran H. Khan, and Smita D. Rajani. 2010. Pharmacological evaluation and characterizations of newly synthesized 1,2,4-triazoles. European Journal of Medicinal Chemistry 45 (9) (09): 4293-9.

 

Pathak, Sharad, Tore Wentzel-Larsen, and Birgitta Asjö. 2010. Effects of in vitro HIV-1 infection on mycobacterial growth in peripheral blood monocyte-derived macrophages. Infection and Immunity 78 (9) (09): 4022-32.

 

Reuter, Morgan A., Nicole D. Pecora, Clifford V. Harding, David H. Canaday, and David McDonald. 2010. Mycobacterium tuberculosis promotes HIV trans-infection and suppresses major histocompatibility complex class II antigen processing by dendritic cells. Journal of Virology 84 (17) (09): 8549-60.

 

Rock, M., B. J. Buntain, J. M. Hatfield, and B. Hallgrimsson.  2009.  Animal-human connections, "one health," and the syndemic approach to prevention.  Social Science and Medicine 68 (6):  991-995.

 

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Eggs: Safer for You Than You’d Think Given Recent Stories in the News

They’re recalling  up to 500,000,000 eggs?   Isn’t this an indictment of the U.S. egg industry as a whole?

It might be if that were the total production of the US, but it’s not even close. Last year, according to the U.S. Dept. of Agriculture’s National Agriculture Statistical Service,  the 337, 000,000 laying hens living in the US produced 90,400,000,000 eggs (about 269 eggs per layer, by the way). The recalled number of eggs is less than 1% of the national output, and even among those 500,000,000, it is likely that only a tiny percentage are actually infected. Statistically, the odds are about 1 egg out of 20,000 eggs is infected. ( www.eggsafety.org )

I hear that thousands of people have been made ill from these eggs: what are my chances that I will get salmonella from eating eggs?

As a rule, you are right in thinking that it is possible to get salmonella from eating undercooked eggs, and this is unfortunately one of the most common ways to get salmonella. However the odds are vastly on your  side as opposed to being on salmonella’s. In a 2008 paper (Davis et al, cited below) the odds were given as 1 or 2 people out of 100,000 will get salmonella from undercooked eggs.) This seems a tad too rare, so let’s  divide up the estimated 2010 population of the U.S., 308,000,000,  by the FDA’s estimate that there are 142,000 cases  annually of salmonella caused by eating undercooked  eggs.   This gives you a 1 in 2168  chance of getting undercooked-egg-induced salmonella. That’s cases of illness, not fatalities. Out of this small number, your chances of  actually dying admittedly increase if you are elderly, an infant, or immunocompromised, and pasteurized egg products available to foodservice providers are recommended for venues where large numbers of these groups are served. But remember, the odds of becoming ill or dying from salmonella derived from eggs would be  essentially zero if the eggs were cooked thoroughly, by the way.

What causes this contamination?

A strain of bacteria called Salmonella enteritidis.

Where does that bacterium come from?

It can come from soil, water, or feed, but is found today mostly in poultry manure. It appears to have migrated from rats and mice to poultry a few decades ago. Egg producers and government scientists and health officials have since placed a premium on detecting any signs of rodents in egg producing operations, and in eliminating the vermin, but to some extent the bad genie is out of the bottle. Rodent control still limits the chances of new acute outbreaks of subtypes that have yet to infect layers or show up in eggs.

How does the salmonella get into the egg?

Salmonella enteritidis most commonly lives in the reproductive and intestinal tracts of layers . Eggs are made “inside out” in the sense that whatever pathogens live inside the hen can be transmitted to the eggs growing inside her during egg formation and laying.

Are all parts of the egg equally “dangerous.”

As a practical matter, given that eggs come out of the hen from the same place as her manure, the shell is by far, the most likely part to be contaminated, as it traverses this shared route. This is followed at a great statistical distance  by the egg white, which just happens to have naturally produced inhibitors of the further growth of salmonella (Humphrey & Whitehead 1993) and then, accounting for an  even tinier percentage, would be the yolk.

What do egg producers do to make sure the eggs are safe?

First and foremost, eggs and flocks are tested on a regular basis  and layers known to be salmonella carriers are taken out of production, and their eggs stopped from entering the market.  In some cases, the layers will be given antibiotics until the infection clears. (In other cases, the layers will be destroyed outright.) Any eggs from those layers will be discarded, and even when the infection has passed in successfully treated layers,  the eggs will not be put back into the food supply until the eggs themselves have tested free of antibiotics.

The day-to-day processing of eggs also involves a number of important, practical safety steps. All shell  eggs are thoroughly washed to remove fecal traces. New procedures involving ozone (Perry, Rodriguez-Romo & Yousef 2008), and microwaves (Lakins et al 2008) are being developed as boosters in egg contaminant removal.  Eggs are kept constantly chilled, a seemingly simple step that greatly retards the growth of virtually all bacterial pathogens, including salmonella.

The living conditions of the hens are also continuously inspected and cleaned. The chicken feed and water supply are examined. In all cases of conscientious egg production, the goal is to get the fecal matter away  from the birds and the newly laid eggs as often as possible.

I hear that many US Producers do not vaccinate their hens, while this is done routinely in other countries.  What gives?

A New York Times story headlined “U.S. Rejected Hen Vaccine Despite British Success,” and reported by William Neuman on August 25, 2010, called into question the fact that many U.S. egg producers do not vaccinate their hens in the same way that British egg producers did, virtually eliminating egg-associated salmonella cases over there. But a more careful reading of the story also indicated that the FDA had considered it, but decided that the evidence was not so clear cut as to mandate it nationally. (It’s important to note that the Brits still find salmonella within their hen houses and on the grounds of their farms, and even in some chickens and eggs, and about 500 cases of egg-associated salmonella in humans still crop up annually, although that number   represents a dramatic drop off .) The FDA had  already mandated a number of enhanced hygiene practices on July 9, 2010,  for the egg industry before the outbreak, so it is not as if, the agency has been asleep at the switch. The FDA and the industry’s leading trade organization, the United Egg Producers,  have been partners in safety for decades, according to the FDA’s own  pronouncements.  A recent review of Britain’s success (Snow et al. 2010) cited vaccination as one of the likely reasons, but it also cited washing and disinfecting the hen house, providing cleansing pools of disinfectant  and scrub brushes so that workers could  remove poultry manure from their shoes and boots, using a commercial chicken feed supplier as opposed to a home-grown mixture , and the presence of cats and dogs  to keep the rodent population down as other contributors. While it is not clear whether or not the much larger US egg production facilities use cats and dogs to hunt rodents on site, measure like these are already standard here.

US egg-producing facilities are gigantic and involve caged-birds, and operations like this are banned in Europe,  including within the UK. Will freeing the layers free us from salmonella in their eggs?

According to an  August 25, 2010 column by Angela Wu  in Newsweek entitled “Are Free-Range Eggs Safer: Factory farming has its problems, but evidence is unclear about whether local food is better,”  the story is complicated and the evidence contradictory.  The problem is that the FDA has found salmonella outbreaks at the largest factory farms and at some of the smallest free-range operations, as well as in those mid-sized operations in between. Two pieces of evidence will surprise the back-to-nature enthusiasts: In large caged bird operations, by their very design, manure removal is done more often and much more efficiently: the birds don’t get to soil themselves or the eggs to the same degree. Second, free-range, “pastured” poultry actually has a higher rate of parasitic infections,  so one might wish not to trade the devil you know (salmonella) for the devil you don’t.

Should I give up eating eggs until this is all over?

If you did, you would be giving up one of the most economical, nutritious, and still generally very safe sources of protein, vitamins, minerals, and nutraceuticals. Much wiser might be following the recommendations of a paper by Davis et al 2008, in which they compare common means of cooking eggs at home  in terms of their ability to kill off salmonella (which, ironically because they could not find enough naturally infected eggs, with which to conduct this experiment, they had to go out and artificially infect them). They concluded that hard-boiled, soft-boiled, and eggs poached in dimpled pan suspended over the boiling water and/or steam were safest. Over-easy and scrambled eggs were reasonably safe, with longer cooking times adding to the margin of safety. “Dropped poached eggs,” meaning those let freely slip into simmering boiling or near/boiling water were safe but only if they were immersed for at least  5 minutes. Sunny side eggs, were,  alas, the least safe, although increased cooking time (until the yolk is firmly set) and the use of a pan cover or basting of the yolk with hot cooking oil or grease was thought to be helpful to get the top of the yolk to cook through.

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

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Almonacid, S., R. Simpson, and A. Teixeira. 2007. Heat transfer models for predicting Salmonella enteritidis in shell eggs through supply chain distribution. Journal of Food Science 72 (9): E508-17.

Davis, A. L., P. A. Curtis, D. E. Conner, S. R. McKee, and L. K. Kerth. 2008. Validation of cooking methods using shell eggs inoculated with Salmonella serotypes enteritidis and Heidelberg. Poultry Science 87 (8): 1637-42.

Gurtler, J. B., and D. E. Conner. 2009. Survival and growth of Salmonella enteritidis in liquid egg products varying by temperature, product composition, and carbon dioxide concentration. Foodborne Pathogens and Disease 6 (5): 561-7.

Humphrey, T.J. & A Whitehead. 1993. Egg age and the growth of Salmonella enteritidis. Epidemiology & Infection. 111: 209-291.

Jones, D. R., and M. T. Musgrove. 2007. Pathogen prevalence and microbial levels associated with restricted shell eggs. Journal of Food Protection 70 (9): 2004-7.

Kretzschmar-Mccluskey, V., P. A. Curtis, K. E. Anderson, L. K. Kerth, and W. D. Berry. 2008. Influence of hen age and molting treatments on shell egg exterior, interior, and contents microflora and Salmonella prevalence during a second production cycle. Poultry Science 87 (10): 2146-51.

Lakins, D. G., C. Z. Alvarado, L. D. Thompson, M. T. Brashears, J. C. Brooks, and M. M. Brashears. 2008. Reduction of Salmonella enteritidis in shell eggs using directional microwave technology. Poultry Science 87 (5): 985-91.

Little, C. L., J. R. Rhoades, L. Hucklesby, M. Greenwood, S. Surman-Lee, F. J. Bolton, R. Meldrum, et al. 2008. Survey of Salmonella contamination of raw shell eggs used in food service premises in the United Kingdom, 2005 through 2006. Journal of Food Protection 71 (1): 19-26.

Murchie, L., Xia Bin, R. H. Madden, P. Whyte, and L. Kelly. 2008. Qualitative exposure assessment for Salmonella spp. in shell eggs produced on the island of Ireland. International Journal of Food Microbiology 125 (3): 308-19.

Musgrove, M. T., J. K. Northcutt, D. R. Jones, N. A. Cox, and M. A. Harrison. 2008. Enterobacteriaceae and related organisms isolated from shell eggs collected during commercial processing. Poultry Science 87 (6): 1211-8.

Perry, J. J., L. Rodriguez-Romo, and A. E. Yousef. 2008. Inactivation of Salmonella enterica serovar enteritidis in shell eggs by sequential application of heat and ozone. Letters in Applied Microbiology 46 (6): 620-5.

Roberts-Witteveen, A., B. A. Campbell, T. D. Merritt, P. D. Massey, C. T. Shadbolt, and D. N. Durrheim. 2009. Egg-associated salmonella outbreak in an aged care facility, New South Wales, 2008. Communicable Diseases Intelligence 33 (1): 49-52.

Snow, L.C., R.H. Davies, K.H. Christiansen, J.J. Carrique-Mas, A.J. Cook & S.J. Evans. 2010. Investigation of risk factors for Salmonella on commercial egg-laying farms in Greta Britain, 2004-2005. Veterinary Record 166 (19): 579-586.

Wu, Angela. 2010. Are free-range eggs safer? Newsweek (August 25, 2010). www.newsweek.com/2010/08/25/are-free-range-eggs-safer-.print.html

Octopus Behavior, Intelligence, Learning, Personality, Problem Solving & Consciousness

In a German aquarium this summer, Paul the Octopus, successfully picked the winner of 2010 FIFA World Cup soccer matches being held in South Africa  eight times in a row, including correctly noting an upset win by Serbia over Germany, but then subsequently predicting Germany’s rebound to winning ways until eventually Germany lost to Spain, the ultimate world cup winner, an outcome Paul had also predicted. Click on the following for a picture of Paul and a story entitled “Germany's 'Octopus oracle' keeps perfect record,”  on the official FIFA website.

www.fifa.com/worldcup/news/newsid=1270308/index.html

Paul’s method of prediction was to select a clam from  one of two underwater boxes in one of two adjacent tanks. Each tank was labeled with the national flag of one or the other of opposing soccer teams.  Confounding logic, many German fans felt that the pregame choice by the octopus somehow subsequently caused Germany’s defeat, and monitors of German Internet usage showed heightened activity related to  researching octopus recipes. The Prime Minister of Spain, in response, promised to send his nation’s equivalent of the US Secret Service to guard Paul and keep him from becoming someone’s dinner. The Russians, out of contention for the World Cup early on, demonstrated greater common sense. The state-supported gaming industry offered 100,000 euros for Paul’s services so as to enable them more scientifically to set odds in international sporting contests. The aquarium,  in reaction to all this, announced that Paul would now be going into retirement from sports prognostications, and perhaps would begin a career as a teacher of other young octopuses. This would seem ludicrous, excepting that there have been some papers, in journals as prestigious as Nature,  that indicated that octopuses can learn from one another, just by watching the trial and error procedures of one of their kind (Fiorito & Scotto 1992) .  Could a weekly column in Sports Illustrated or pr pre-game appearances on ESPN be in the works?  Or perhaps has Paul the Octopus all his hands full already.

How Smart Are Octopuses?

There is a general consensus that octopuses are the smartest of invertebrates, and indeed, they may be smarter than many vertebrates. They can negotiate mazes, and retain a memory of successful vs. blocked pathways (Hvorecny et al 2007). The can learn the location of a suitable hideaway in an experimental tank, be  transferred from the tank to another for a week, and then instantly find the hideaway in the original tank when they are returned to it.  Should this hideaway be closed to them, the octopuses  can then be taught a new hideaway’s location, and retain a subsequent memory of it (Boal et al. 2000).

Octopuses have definite favorites in the types of clams or mussels they eat, but it is conditional, with the principal determinant being the degree of difficulty in getting the shell opened or otherwise penetrated (Anderson & Mather 2007).  In a three way choice, the easiest to open bivalves were consistently the most eaten, the next easiest to open were second, and the most difficult to open were last. However, food preferences for these same octopuses flipped when all three bivalves were presented in equal numbers in an already-opened state. One of the more difficult-to-open species became the new favorite. However, when ordinarily easy-to-open clams or mussels are glued and wired shut experimentally, octopuses once again shift their preferences in order to minimize effort. What’s important is that they appear to generalize from initial trials in each round of changed circumstances. When they encounter types that they find that are hard to open in a particular round, they avoid them subsequently during that round, saving their energy by redirecting their foraging to easier types.

To bolster the argument for octopuses making conscious adjustments and generalizing knowledge from specific examples, it was found that octopuses switched strategies for getting at the actual meat in a clam or mussel: sometimes pulling the shell apart, sometimes smashing the shell, sometimes drilling through the shell and at other times chipping away at the shell’s rim. All of these represented shifts in tactics to difficulties encountered.  When one method did not work for a particular species of clam  or mussel, another method might be tried, and once one method proved to be the right tactic for a particular species, that  method of penetration became associated with that species. Indeed, in a final grace note to the argument, octopuses apparently learned to target where to drill their holes so as to get to the most vital internal organs of the clam or mussel most directly, so that their  subsequent injection of poison would cause the shellfish to open up most quickly.

Can Octopuses Use Tools?

One popular video currently making the rounds  on YouTube, entitled “Coconut-Carrying Octopus” www.youtube.com/watch?v=1DoWdHOtlrk and backed by a scientific article in Current Biology  (Finn, Tregenza & Norman 2009) shows that octopuses “claim” coconut shells that have been split apart as part of copra processing and been cast into the sea. They have developed a way of stilt walking across the ocean floor with the shell hanging beneath them, so as to transport the half-shells rather long distances to a preferred site, and then fashioned them into rather safe shelters. 

Some critics have argued that the use of “found objects” like these shells is not the same as fashioning them into tools, but they have yet to explain away the peculiar habit of octopuses for quite literally playing with Lego toys in aquaria (Kuba et al. 2006) . These toys are in no way food-like objects, nor do they represent  prey or serve as practice dummies for hunting. In fact, they resemble nothing in their natural environment, and yet, they become objects of continuing interest in both adult and juvenile octopuses. Octopuses have even  learned on their own, how to unscrew jars and bottles.

“Hand-Eye”  Coordination & Specialization within the Octopus Brain

One of the relatively recent findings in studies of octopus capabilities is the fact that although they do not have specialized tentacles like squid for trapping prey, they do develop special abilities within their otherwise anatomically identical legs or arms, and that this seems to be done in conjunction with having a favored eye they use for specific tasks. In a series of papers (Byrne, Kuba & Meisel 2004, Byrne et al 2006a, 2006b) it was clearly shown that octopuses have a preferred eye that they use more often than its opposite counterpart, and this seems to correlate with tasks routinely assigned to a given arm or set of arms. Anterior arms were used to probe and reach out for novel objects. Octopuses also seemed to favor a particular arm when trying to negotiate a maze. Moreover some octopuses used different legs or arms for sidewise motion, versus back and forwards, despite the fact that it would take little energy to rotate their bodies and choose a different sequence. This all points to an eye-to-brain-to-arm (or leg) circuitry that indicates that the octopus is capable of designating particular parts of their very large brains to serve differentially, specific functions, much as mammals do.

Do Octopuses Have Distinct Personalities Or Temperaments?

There have been many proponents of the theory that individual octopuses do, in fact, have different personalities. The most vocal in support of this notion are the many aquarium personnel who have observed that some octopuses of the same species are aggressive and easy to anger, while others are shy and gentle. Some are quick learners  who love to play while others are  seemingly annoyed by changes in routine and defensive about new objects in their watery domains. Some come out from hiding in their aquarium tanks to look right back at the people who are looking at them. Some get along with other octopuses in large tanks while others view  others of their kind as intruders that have to be put in their place.  Most remarkable are octopuses who habitually break out of their own tanks, traverse the floor to another tank they have been eyeing, enter that tank, and consume all the crabs or clams to be had there, before moving on to another tank or returning to their assigned one.

By far, the most heavily published of experts in areas of octopus intelligence, behavior and temperament is the Canadian researcher Jennifer Mather of the University of Lethbridge, in Alberta,  ironically  a  province that does not even have access to an ocean (She has repeatedly acknowledged the generous access she has been granted over the years to the Seattle Aquarium). This landlocked academic appointment has not stopped her from making the case rather convincingly that individual octopuses develop their personalities or temperaments over time, that genetically related octopuses tend to have similar behavioral traits, and that  at least some  invertebrates, particularly the category of cephalopods (octopuses, squid and cuttlefish) which have very large brains, use them to explore their environments in a conscious manner,   solving  problems, and building  a memory bank of experiences on which they will depend to improve their lives…….and yes, to have a little fun, now and again.

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 USA

Voice: 479-409-0021

Fax: 479-575-4592

 Anderson, Roland C., and Jennifer A. Mather. 2007. The packaging problem: Bivalve prey selection and prey entry techniques of the Octopus enteroctopus dofleini. Journal of Comparative Psychology 121 (3) (08): 300-5.

Boal, Jean Geary, Andrew W. Dunham, Kevin T. Williams, and Roger T. Hanlon. 2000. Experimental evidence for spatial learning in octopuses (Octopus bimaculoides). Journal of Comparative Psychology 114 (3) (09): 246-52.

Byrne, Ruth A., Michael J. Kuba, and Daniela V. Meisel. 2004. Lateralized eye use in Octopus vulgaris shows antisymmetrical distribution. Animal Behaviour 68 (5) (11): 1107-14.

Byrne, Ruth A., Michael J. Kuba, Daniela V. Meisel, Ulrike Griebel, and Jennifer A. Mather. 2006. Does Octopus vulgaris have preferred arms? Journal of Comparative Psychology 120 (3) (08): 198-204.

Byrne, Ruth A., Michael J. Kuba, Daniela V. Meisel, Ulrike Griebel, and Jennifer A. Mather. 2006. Octopus arm choice is strongly influenced by eye use. Behavioural Brain Research 172 (2) (07): 195-201.

Byrne, Ruth A., Michael Kuba, and Ulrike Griebel. 2002. Lateral asymmetry of eye use in Octopus vulgaris. Animal Behaviour 64 (3) (09): 461-8.

Cheng, Mary W., and Roy L. Caldwell. 2000. Sex identification and mating in the blue-ringed octopus, Hapalochlaena lunulata. Animal Behaviour 60 (1) (07): 27-33.

Edelman, David B., Bernard J. Baars, and Anil K. Seth. 2005. Identifying hallmarks of consciousness in non-mammalian species. Consciousness and Cognition: An International Journal 14 (1) (03): 169-87.

Finn, J.K., T.Tregenza & Mark D. Norman. 2009. Defensive tool-use in a coconut-carrying octopus. Current Biology 19 (23): R1069-R1070.

Fiorito, Graziano; and Pietro Scotto. 1992. Observational learning in Octopus vulgaris. Science. Vol. 256(5056), 545-547.

Glanzman, D.L. Octopus conditioning: A multi-armed approach to the LTP- learning question. Current Biology 18 (2): R527-R530.

Gosling, Samuel D., and Oliver P. John. 1999. Personality dimensions in nonhuman animals: A cross-species review. Current Directions in Psychological Science 8 (3) (06): 69-75.

Hochner, Binyamin, Euan R. Brown, Marina Langella, Tal Shomrat, and Graziano Fiorito. 2003. A learning and memory area in the octopus brain manifests a vertebrate- like long-term potentiation. Journal of Neurophysiology 90 (5) (11): 3547-54.

Huffard, Christine L., Roy L. Caldwell, and Farnis Boneka. 2010. Male-male and male-female aggression may influence mating associations in wild octopuses (Abdopus aculeatus). Journal of Comparative Psychology 124 (1) (02): 38-46.

Hvorecny, Lauren M., Jessica L. Grudowski, Carrie J. Blakeslee, Tiffany L. Simmons, Paula R. Roy, Jennifer A. Brooks, Rachel M. Hanner, et al. 2007. Octopuses (Octopus bimaculoides) and cuttlefishes (Sepia pharaonis, S. officinalis) can conditionally discriminate. Animal Cognition 10 (4) (10): 449-59.

Ikeda, Yuzuru. 2009. A perspective on the study of cognition and sociality of cephalopod mollusks, a group of intelligent marine invertebrates. Japanese Psychological Research 51 (3) (09): 146-53.

Kuba, Michael J., Ruth A. Byrne, Daniela V. Meisel, and Jennifer A. Mather. 2006. When do octopuses play? Effects of repeated testing, object type, age, and food deprivation on object play in Octopus vulgaris. Journal of Comparative Psychology 120 (3) (08): 184-90.

Mather, Jennifer A. 2008. Cephalopod consciousness: Behavioural evidence. Consciousness and Cognition: An International Journal 17 (1) (03): 37-48.

Mather, Jennifer . 2006. Behaviour development: A cephalopod perspective. International Journal of Comparative Psychology 19 (1): 98-115.

Mather, Jennifer A., and Roland C. Anderson. 1999. Exploration, play, and habituation in octopuses (Octopus dofleini). Journal of Comparative Psychology 113 (3) (9): 333-8.

Mather, Jennifer A., and Roland C. Anderson. 1993. Personalities of octopuses (Octopus rubescens). Journal of Comparative Psychology 107 (3) (09): 336-40.

Mather, Jennifer A. 2008. To boldly go where no mollusk has gone before: Personality, play, thinking, and consciousness in cephalopods. American Malacological Bulletin 24 (1/2): 51-58.

Meisel, Daniela V., Ruth A. Byrne, Michael Kuba, Jennifer Mather, Werner Ploberger, and Erhard Reschenhofer. 2006. Contrasting activity patterns of two related octopus species, Octopus macropus and Octopus vulgaris. Journal of Comparative Psychology 120 (3) (08): 191-7.

Minakata, H., S. Shigeno, N. Kano, S. Haraguchi, T. Osugi, and K. Tsutsui. 2009. Octopus gonadotrophin-releasing hormone: A multifunctional peptide in the endocrine and nervous systems of the cephalopod. Journal of Neuroendocrinology 21 (4) (04): 322-6.

Shomrat, T. I. Zarrella, G. Fiorito, & B. Hochner. 2008. The octopus vertical lobe modulates short-term learning rate and uses LTP to acquire long-term memory. Current Biology 18 (5): 337-342.

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Wood, James B., and Roland C. Anderson. 2004. Interspecific evaluation of octopus escape behavior. Journal of Applied Animal Welfare Science 7 (2): 95-106.

Cancer Research & Treatment 2000-2009: A Listing of Some of the Most Cited Articles of that Decade & Highlights of Some of their Findings

By 2005, as expressed in a major review by Adams and Weiner,  it  had become clear that monoclonal antibodies have proven to be one of the most promising of new biological chemotherapies.  That term may seem an oxymoron in the old dichotomy which separated biologicals (such as vaccines derived from sera or killed cells) from chemotherapeutic agents (which were synthesized from common chemicals usually derived from petrochemicals or alcohols). But the new usage indicates that they are derived from cell culture methods and are then chemically stabilized so as to be able to be administered in reliable dosages.) The key to the effectiveness of monoclonal antibodies appears to be their ability dock onto receptors that are needed for cancer cells or tumors to thrive. In doing so, they displace growth factors or hormones, often leading to tumor regression. In addition, monoclonal antibodies often can be used with traditional cytotoxic chemotherapies, or radiation,  without interfering with their effects.

Epidermal growth factor receptors (EGFR) have been found in excess in a number of tumor classes, and drugs targeted against them ( e.g  erlotinib, Tarceva™) have worked with spotty success among some non-small-cell cancers of the lung or pancreas. But there  were no standards for pre-testing tissues to see if the tumors were, in fact, susceptible. This was an omission corrected by an expert panel (Eberhard, Giaccone and Johnson 2008) who were setting up clinical trials and needed to have benchmarks.

One of the happy but still puzzling situations encountered in oncology are a small number of types of  cancers that start out aggressively growing but then spontaneously become self limiting. A 2007 review by Bartek, Bartkova and Lukas discussed the DDR (DNA damage response)  with the idea that a new line of therapy might well involve, instead of trying with limited success to kill off all cancer cells, stimulating surviving cancer cells to initiate this DDR-induced quiescence.

Telomeres and telomerases were profiled in 2008 by the French team of DeCian, Lacroix, Douarre et al,   as representing a good therapeutic target because it is thought that many cancers result from a decrease in the ability of chromosome basically to keep  the ends of their chromosomes (their telomeres)  intact, or at least forestall the rate at which they fray and shrink.

Along similar lines, it was suggested in a 2005 review by Dean, Fojo, and Bates that the resilient pluripotential stem cells we virtually worship in biotechnology  as the hope for replacing many damaged cells and tissues in diseases like Parkinsonism, have a darker side, and it might be warranted to target them in some forms of cancer. The very traits that make them able to survive undifferentiated and less vulnerable, and then  later  to  take on many identities,  tend in cases like hematopoietic cancers (leukemia, lymphoma and multiple myeloma)  to  protect them from being killed during chemotherapy. Those stem cells may contain what the authors call an overabundance of adenosine trisphophate (ABC)  cassettes.  In some cases, ABC cassettes  promote resistance to chemotherapeutic agents by literally pumping them out of the stem cells  which, once the existing cancer cells have been killed off, may replace them as cancer cells, instead of as healthy tissue.

Transforming Growth Factor beta (TGF-beta) is an essential component of normal activities that involve the growth and branching out of healthy human cells into tissues and then into organs. In particular, helps them develop their own localized blood supply to keep them going. A 2005 study by Elliott and Blobe suggests that unfortunately very high levels of TGF-beta are  detectable in early cancer biopsies, and that monitoring these could help in staging cancers, and disrupting them, may cut off their growth.

While CAT scans and MRIs had long  become effective and routine in the diagnosis and staging of cancers, arguably the fastest rising technology of the 2000s  was F18- FDG PET (Fluorodeoxyglucose Positron Emission Tomography). The combination of trace radioactivity and glucose function enable not only a 3D visualization of location, but also provide information on metabolism at the site. According to Fletcher, Djulbegovic, Benjamin et al it served as an excellent tool for initial diagnosis of cancers of the head and neck, pancreas and unknown primary tumors, and was a good measure for scoring the staging or recurrence of breast, colon, esophageal, and other tumors initially diagnosed by other means.

 

Breast Cancer

Given the major advances made in understanding and treating several estrogen receptor (ER) dependent breast cancers, it surprised many that even  as  the decade waned that there was still a great deal of  tumor resistance to the usual hormone receptor blocking therapies. The thinking was that without these hormones having a home at which they could lodge, that the stimulus they provided to further breast tissue growth would be shut down and tumors would shrink and perhaps disappear. But in 2008  Arpino, Wiechman, Osborn and Schiff  explored  how human epithelial growth receptors  (HER)    provided what they termed  “cross-talk” with estrogens in search of a place to go, leading to  alternative pathways for  these  hormones to dock despite the shut down of ER.  This study  led towards further recognition of  an important subtype of breast cancer  ( HER-susceptible) requiring an alternative treatment with  newer drugs like transtuzumab (Herceptin™) to cut off that alternate route.

One of the most effective families of breast cancer chemotherapeutic agents, are the anthracyclines,  with doxorubicin, (Adriamycin™) probably being the best known. Nonetheless one of the most successful new class of breast cancer drugs of the 1980s and 1990s, particularly in the more aggressive breast cancers  have been the taxanes  (historically derived from rather rare yew bark, but now made by semi-synthetic methods that did not endanger the species and have since reduced their costs) . These taxanes were often administered only after the anthracyclines seemed to stop working, and the disease returned.  A 2008 meta-analysis by DeLaurentis, Cancello, D’Agostino et al, demonstrated that a concurrent combination therapy of anthracyclines and taxanes (as opposed to a sequential one) increased the intervals when  patients with  early but aggressive breast cancers patient  stayed in remission and raised their overall survival.

Colorectal Cancer

Testing the character of a tumor to determine the right course of treatment is standard for a wide variety of tumors, and two of the most common are IHC (ImmunoHistoCompatability) complex and its more recently developed competitor FISH (Fluorescent In-Situ Hybridization) are sometimes used for biopsies. In some cases, such as breast and lung cancers, a positive test on the IHC  is automatically sent for confirmation by the FISH, but it is not unknown for the two test to conflict on whether or not a therapeutic  attack based on the biopsy indicating a high level of Epidermal Growth Factor Receptors (EGFR) would be the best course. A 2005 study by Chung, Shia, Kemeny et al determined that no matter whether the IHC test was positive or negative, once a course of a more conventional chemotherapeutic agent such as iriniotecan (Camptesar™) had failed, then progression towards one of the newer EGFR inhibitors, such as cetuximab (Erbitux™) seems warranted, because many IHC negative tumors seemed to have responded to the Erbitux ™ despite that test.

In a 2007 paper Giantonio, Catalano, Meropol et al trialed three courses of treatment for colorectal cancer. One plan involved a traditional cocktail of oxaliplatin (Eloxatin™), Fluouracil (Adrucil™ and Fluoroplex™) and folinic acid (Leucovorin™), a combination known in chemotherapy circles as FOLFOX4. The second plan involved the use of newer anti-angiogenic drug bevacizumtab (Avastin™) on its own. A third plan combined FOLFOX4 and Avastin ™. The Best outcomes came form the addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin. This four-way combination   improves survival duration for patients with previously treated metastatic colorectal cancer, although as with many chemotherapeutic regiments: nausea, hypertension and some rectal bleding were side-effects that had to be managed.

 

Gastrointestinal  Cancer

One of the most common of stomach tumors as the gastrointestinal stromal tumors (the GISTs). GISTs are often  detected only when they become rather large by which time they tend to displace the alignment and sometimes the smooth function of  nearby organs in the area. While usually treated by surgical removal, and often with good results, they have long resisted follow-up chemotherapy. But by 2005, a consensus recommendation of European sarcoma societies had endorsed imatinib (Gleevec™) a drug previously used with some success in chronic myelogenous leukemia,  known to be a disruptor of tyrosine kinase, an enzyme absolutely essential to the progression of the cancer, as a post-surgical treatment.

Cancers of the Head and Neck

In 2008, Argiris, Karamouzis, Raben and Ferris reviewed the current state of sqamous cell head and neck cancer etiology and treatment. Certain traditional contributing factors such as tobacco use and heavy (and often concurrent) alcohol intake remained  at the top of the list, but human papilloma viruses became more and more often implicated, and became formalized as an important subtype. While a variety of traditional chemotherapeutic agents and radiation therapy continued  to be the first line of treatment (Fakhry, Westra, Cmelak et al 2008)  epidermal growth factor receptor inhibitors (e.g. cetuximab, Erbitux™,  showed increasing promise (Bonner, Harari, Giralt et al 2006, Burtness, Goldwasser, Flood et al 2005).   

 

Liver Lancer

In the western world, most liver cancer has been secondary to prolonged alcoholism, but in the Far East, where hepatitis remains especially endemic a substantial number of patients seem to develop it  after chronic viral infection. A  2009 protocol has been reported by Cheng, Kang, Chen et al for the prolonging of life of patients with advanced hepatocellular cancer ,  with a  drug that had previously been shown to have good results against kidney cancers,  sorafenib (Nexavar™). While the life extension offered is still only about  six months, this is an improvement over the 4 months common with placebo, or other therapies in use, with a relatively tolerable incidence of side-effects. 

A greater life extension was achieved in patients with gastroeneteropancreatic cancers. While slow-growing, most patients die within four years. But a radioactively labeled growth stopper, a somatostatin analog called lanreotide (Somatuline™) has extended the life of some patients up to six.

Lung Cancer

Lung cancers have a spotty record in terms of which drugs will lengthen life with the fewest side-effects, and most patients die within a fairly short time despite treatment. But in 2006, Cappuzzo, Hirsch, Rossi et al and in 2008, Hirsch, Herbst, Olsen et al reported that when patients with non-small-cell lung cancer (NSCLC)  had biopsies that included a fluorescent in-situ hybridization (FISH) test of the tissue, those patients who were positive for epidermal growth factor receptors (EGFR) could be treated better with cetuximab (Erbitux™) a drug otherwise used successfully for  colorectal and head and neck cancers. EGFR positive patients  whose treatment included Erbitux™ tended to live eight months longer than patients negative for EGFR treated with  a similar regimen.

Ovarian Cancer

Apart from the  Pap smear early detection method, ovarian cancer  has traditionally been found only when it had become painful, usually at an advanced stage with a  poor prognosis, and an uncertain chemotherapeutic path. In 2008, however, Garcia, Hirte, Fleming et al advanced the idea that a combination therapy of a very traditional (1950s) alkylating agent cyclophosphamide (Cytoxan™) and a newer monoclonal antibody bevacizumab (Avastin™)  that blocked angiogenesis in tumors (cutting off their blood supply) in colorectal cancers had excellent results blocking ovarian cancer recurrences and was well worth further exploration. A 2006 study in the New England Journal of Medicine  by Armstrong, Bundy, Wang et al reported that the use of a combination of some traditional chemotherapeutic agents delivered through differing routes can have significantly different results. As compared with the traditional administration of  paclitaxel and cisplatin via the intravenous route, intravenous paclitaxel plus direct intraperitoneal injections of cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer, by a period of several months to years. This effect held true even though many patients disliked and even discontinued the direct injections owing to greater pain, nausea and other side effects.  The longer after the treatments concluded the more that patients reported that these side-effects dissipated, and in retrospect, seemed to make worthwhile their initial suffering.

Pancreatic Cancer

Pancreatic cancers have a very poor prognosis and most chemotherapeutic strategies have very limited life-prolonging potential. In 2008, Kulke, Lenz, Meropol et al  tried using sunitinib (Sutent™)  a drug that targets VEGF (vascular endothelial growth factors and their receptors) and PDGF (platelet derived growth factors) and which had  previously shown good results in fighting gastrointestinal stromal tumors and in renal cell carcinonoma. It  extended the life of pancreatic cancer patients whose tumors were of the neuroendocrine type for a whole year.  It has shown less promise in dealing with carcinoid tumors of the pancreas, but these began showing good response to somatostatin analogs like lanreotide (Somatuline™) as noted earlier.

Prostate Cancer

Most prostate cancers are slow moving, but certain subtypes become more aggressive and require treatment sooner than the norm. The treatment regimes often  include some combination of surgery, cytotoxic chemotherapy, radiation, and increasingly,  male hormone suppression.  While none of these treatments is without the potential for incontinence and impotence, androgen suppression has the added problem of a certain feminization of features and in some cases cognitive declines, bone thinning and increased cardiovacular risk A 2008 analysis by D’Amico, Chen, Renshaw et al reported  that in a study of 206 men with localized but unfavorable risk prostate cancer,  that androgen suppression did not markedly preserve life notably longer, and might be omitted if its addition to side-effects seemed to onerous for the patient to bear.

Skin Cancer

Melanomas are among the most common cancers, and they can become fatally invasive, if left untreated. Fortunately they can often be cut, frozen or burned off the skin, but the question remains whether or not the melanoma will recur despite what appears to be “clean edges.” Stage III melanomas are fairly advanced, and have a high rate of recurrence,  but there has been no consensus as to the best follow-up after surgical removal, and doing nothing but watchful waiting has been shown to be about as effective as other more aggressive therapies. Eggermont, Suciu, Santinami et al demonstrated in 2008 that a post melanoma removal treatment plan that included pegylated interferon alfa-2b (Peg Intron™) substantially increased recurrence-free survival rates.

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

University of Arkansas Libraries 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

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