Aging, Spamming, Drugging, Helminths, and A Controversial Therapeutic Approach (Fascinating Articles This Week)

There are always interesting things to read around here, like the current issue of _Academe: Magazine of the American Association of University Professors_. Among other related content is “Diagnosing Conflict-of-Interest Disorder: Big Pharma works in subtle but powerful ways inside the pages of the Diagnostic and Statistical Manual of Mental Disorders.” http://www.aaup.org/AAUP/pubsres/academe/2010/ND/feat/cosg.htm

Here's the reason that I care about this seemingly boring topic: the DSM has a lot to do with how “mental illness” is understood and treated, and this trickles down to laypeople like us when psychiatrists diagnose our children with any number of disorders, and also when they recommend treatment/drugs. Because this is so important, I have quoted a substantial amount of the article below:

“[There are] recent questions raised by investigative journalists and policy makers about the extent of industry influence on the diagnostic guidelines of the American Psychiatric Association (APA). Much is at stake: the APA’s Diagnostic and Statistical Manual of Mental Disorders (DSM) is often referred to as the bible of psychiatric disorders because of its enormous influence on clinical practice...The APA also produces and disseminates clinical-practice guidelines directly tied to DSM diagnoses. Thus, publication of the DSM-V, scheduled for 2013, will not only generate millions in additional revenue to the APA but also affect what health practitioners prescribe to patients.”

“In response to concerns about conflicts of interest expressed by researchers, clinicians, patient groups, and even people who served on committees for previous revisions to the DSM, the APA has increased transparency. Specifically, the APA has required all taskforce and panel members to post disclosure statements in which they identify financial ties to industry. The transparency provides an opportunity to assess the subtle but powerful ways pharmaceutical-industry influence may continue to play a role. It is critical not only to look at the proposed changes but also to examine what remains unchanged sixteen years after the DSM-IV and a decade after the DSM-IV-Text Revision was published.

“At least three areas of concern emerge from a review of the first draft of the DSM-V.

“1. Despite transparency, financial associations with industry remain robust. ...Nearly 70 percent of the DSM-V task-force members report having ties to the pharmaceutical industry. This represents a relative increase of 20 percent over the proportion of DSM-IV task-force members with such ties just a decade ago. But it is not only task-force members who have financial relationships with Big Pharma. Of the 137 DSM-V panel members (that is, workgroup members) who have posted disclosure statements, 77 (56 percent) reported industry ties, such as holding stock in pharmaceutical companies, serving as consultants to industry, or serving on company boards—no improvement over the 56 percent of DSM-IV panel members who were found to have such industry relationships. Some DSM-V panels still have a majority of members with industry ties...

“2. Attention to adverse side effects of medications is virtually nonexistent. Previous editions of the DSM, including the latest text revision published in 2000, glossed over the side effects of psychotropic medications. Only two of more than seven hundred pages of the main body of the DSM-IV-Text Revision deal with diagnosing side effects of psychotropic medication.

“...Absent entirely is a discussion of life-threatening side effects of medication, such as diabetes and other metabolic conditions. A review of the recently proposed changes to the DSM at www.dsm5.org indicates that these omissions will be continued in the next edition. Information made publicly available by the APA suggests that the proposed revisions continue to be relatively silent on the issue of iatrogenic harm (that is, the harms or adverse effects that may result from the treatment). In fact, many of the revisions seem only to reinforce and expand the primacy of medications in the management of psychiatric disease. ...This...is especially disconcerting given the extreme profitability of the psychotropic drug market and the burgeoning data regarding the highly problematic, even potentially deadly side effects--hyperglycemia, diabetes, metabolic syndrome, cardiac problems, sexual dysfunction--of commonly prescribed psychiatric medications, such as antidepressants and atypical (or “secondgeneration”) antipsychotics. It is of additional concern that antidepressants are increasingly being prescribed for conditions other than depression—from hot flashes to headaches and back pain. Similarly, prescriptions of atypical antipsychotics have significantly increased since the U.S. Food and Drug Administration (FDA) approved their use not only for schizophrenia but also for bipolar disorder and depression. More people than ever before are being exposed to these agents, including children and adolescents.

“3. There are significant gaps in the disclosure policy. Unrestricted research grants were excluded from the APA’s disclosure requirements, even though the monies from such grants can total hundreds of thousands of dollars or more. There also are no policies for managing indirect financial ties, such as industry funds that are pooled and given to academic departments, hospitals, and medical schools. Moreover, DSM panel members are allowed to resume their financial relationships with industry as soon as their tenure on the DSM panels is over.”

If you think the industry is smart enough to regulate themselves, here's a little fairytale:

“...Eli Lilly was originally scheduled to lose its patent on its blockbuster drug Prozac in 1999. Lilly was able to get another extension (by patenting a new formulation) six months before its original patent was about to expire. However, the pharmaceutical company had no way of knowing ahead of time that the FDA would grant approval for the new formulation and thus was certainly motivated to find another way to continue to enjoy Prozac’s multibillion-dollar profits. In November 1999, Lilly submitted, and the FDA subsequently approved, its application for fluoxetine hydrochloride (Prozac) for the treatment of Premenstrual Dysphonic Disorder (PMDD). Shortly thereafter, women were inundated with direct-to-consumer advertisements encouraging them to consider the possibility that they might have PMDD. One of the most widely run TV ads showed a frustrated and irritated woman outside a supermarket trying to pull a stuck shopping cart out of its lineup. The voice-over in the ad states, 'Think it’s PMS? It could be PMDD. PMDD affects millions of women . . . but the good news is that your doctor can treat PMDD with a new treatment called Sarafem.' What women were not told in these ads was that the psychotropic medication produced by Eli Lilly to treat PMDD was Prozac, relabeled as Sarafem and manufactured in pink and lavender pills...”

“The DSM can play a subtle but key role in the FDA’s decision about whether to approve a new psychotropic drug. This is because, as Angell points out, the FDA does not simply grant approval of new medications; it grants approval based on a particular use or condition. When the FDA considers a new indication for a drug, there must be empirical support or well-accepted diagnostic criteria for that indication. For example, the minutes from the November 1999 FDA meeting show that Lilly had to provide evidence that PMDD was 'distinct from other disorders that are characterized by affective symptoms such as, for example, major depressive disorder.'

“The design and structure of the DSM--what has been referred to as a 'checklist' approach-not only conflates mental health treatment with psychopharmacology but also may create an industry-friendly situation...

“In an industry-dominated climate, assessing the validity of new DSM disorders becomes even more complex. As the Sarafem story makes clear, the lack of biological markers for psychiatric illnesses may set the stage for patent extending possibilities or approval of 'me-too' psychotropic drugs that are not necessarily in the public’s best interest. It is noteworthy that, in December 2000, the FDA sent a warning letter to Eli Lilly, mandating that Lilly cease using this ad for the following reasons: 'The imagery and audio presentation of the advertisement never completely define or accurately illustrate premenstrual dysphoric disorder (PMDD) and there is no clear distinction between premenstrual syndrome (PMS) and PMDD communicated. . . . The advertisement is lacking fair balance because the graphics accompanying the audio presentation of the risk information are very distracting and minimize the important risk information.'

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Here's an interesting blog all about the fascinating topic of Inflammation. He's not the best writer, but this professor of Molecular, Cellular and Developmental Biology does discuss interesting things. For example, here's an excerpt from an article on Aging and Gut Flora: http://coolinginflammation.blogspot.com/2010/04/aging-gut-flora.html

“...The gut flora of an individual reflect the bacteria that have entered the GI tract, nutrients available to the bacteria in previous meals, bacterial growth regulators released by the gut, exposure to antibiotics, exposure to phytochemicals and gut transit time.

“Gut flora appears to be amazingly diverse from individual to individual with thousands of bacterial species inhabiting humans worldwide and about 150 species in each individual. The same species remain in an individual for long periods of time regardless of diet. The dominance of particular species depends on recent diet. Major changes can result from antibiotics or gut diseases, e.g. Crohn’s.

“Bowel stools are made up predominantly of bacteria and not undigested plant parts, i.e. fiber. Fiber is made up of plant polysaccharides that are not digested by salivary, stomach or pancreatic enzymes, e.g. proteases and amylases that degrade proteins and starch. Fiber polysaccharides pass into the colon where they are digested by gut flora. People with constipation usually have disrupted gut flora, e.g. wiped out by antibiotics, and so the minimal volume of remaining undigested fiber is all that passes out in compact, dehydrated lumps. If gut flora have been exposed to a particular type of fiber and bacteria having the needed enzymes have been brought into the gut previously, then the fiber is digested to sugars that feed the gut bacteria. The increased population of bacteria is what makes up normal, hydrated bowel stools.

“...Bacteria grow quickly and with ample nutrients gut bacteria can double in number in about an hour. Bacterial species are usually defined by the ability to utilize various carbohydrates or polysaccharides as nutrients. Depending on the food eaten, nutrients favor the growth of particular bacterial species and the gut flora population changes dynamically. New species are incorporated into the gut flora only if they find their way into the gut on food, e.g. riding on fresh, uncooked vegetables, and food provides nutrients that can permit the new bacteria to grow. It will take several meals for new bacteria to reach appreciable numbers. In the mean time the new fiber may be partially degraded and produce chemicals that disrupt other gut flora and cause bloating symptoms of food intolerance. This is not an allergic reaction of the immune system. It just takes time and persistence to permit the gut flora to adapt. Most people systematically make themselves intolerant to particular foods by over-reacting to initial maladaption of their gut flora to the new food. If they persisted with progressive exposure to diverse foods, their gut flora would adapt.”

This is interesting to me, because it suggests that even a person with severe gut dysbiosis (i.e. profound overgrowth of opportunistic/pathogenic organisms) has the potential, if they haven't utilized any extreme measures (like antibiotics), to restore a better balance--because the good guys are _already there_, just existing in very small populations. It's just a simple matter of eating the best foods possible, to nudge our bodies toward heath and encourage these bugs to get healthy, and reproduce, and take over their rightful place as the Ones in Charge. :) Eight months into GAPS, I can say blithely, Piece of Cake! :)

But what if the Good Bugs have been wiped out, by antibiotic use or other means? Not only do I think we need constant infusions of probiotic-rich foods and a dietary overhaul, but I'm pretty fascinated by the idea of gut-flora transplants between individuals (see blog reference, below).

Also, here's the same blogger, discussing helminths: http://coolinginflammation.blogspot.com/2010/04/helminths-oligosaccharid...

“...Most of the immune cells of the body are present in the lining of the gut. It is in the gut that various immune cells continue to develop for their various roles, including controlling immune reactions to self antigens and to common food molecules. Immune cells in the gut are exposed to some food molecules and bacteria that leak through the cells of the intestinal villi. Responding to these common antigens by inflammation can lead to inflammatory bowel disease. This pathological over-responsiveness is normally avoided by development of regulatory T cells, Tregs, that suppress immune responses to common food molecules and to surface antigens of common bacteria.

“Gut bacteria are needed for the normal function of the immune system. Oddly, Helicobacter pylori, Hp, the cause of stomach ulcers and cancer, also stimulates the development of Tregs. Thus, the pathology of Hp may result not from its presence, but rather from how it is growing. Since Hp uses hydrogen gas produced by Klebsiella in the lower bowel and hydrogen production is dependent on dietary starch, then it follows that the pathological behavior of Hp may be dependent on dietary starch. A low starch diet may actually result in Treg stimulation from Hp and a reduction in allergies and autoimmune diseases.

“Immunological tolerance is also stimulated by parasitic worms, Helminths. Helminth infestations, therefore, reduce allergies and autoimmune diseases and may contribute to the hygiene hypothesis to explain the prevalence of allergies, autoimmune and other inflammation-based degenerative diseases in modern societies. Examination of worms to find the molecules responsible for inducing immunological tolerance has identified complex surface and secreted oligosaccharides (small sugar chains) as the active molecules. Helminth oligosaccharides mimic human cell surface oligosaccharides and bind to carbohydrate-binding, lectin, receptors on immune cells to stimulate Treg development.

“There are many implications of the modulation of the immune system via oligosaccharides. Note that related oligosaccharides are components of human milk and prepare the gut and develop the immune system. This explains why formula, which lacks these unique oligosaccharides, results in aberrant gut flora, contributes to neonatal necrotizing colitis and supports the development of allergies and autoimmune diseases. In contrast, judicious use of self or Helminth oligosaccharides may provide a means of restoring the function of damaged immune systems and therapy for allergies and autoimmune diseases. Also note that the critical use of lectins, which have oligosaccharide-binding sites rich in aromatic amino acids to bind the hydrophobic faces of the sugars, will also bind and provide entry into immune cells for allergens and autoantigens that have triplets of basic amino acids. The binding sites of lectins should also bind many aromatic phytochemicals. Immunomodulation by phytochemicals may result from interference with or mimicking the binding of oligosaccharides to lectin receptors.

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Some very fun resources, sent along by Sage: http://digital.lib.msu.edu/projects/cookbooks/html/browse.html

“The Michigan State University Library and the MSU Museum have partnered to create an online collection of some of the most influential and important American cookbooks from the late 18th to early 20th century. The goal of this project is to make these materials available to a wider audience.

“Digital images of the pages of each cookbook are available as well as full-text transcriptions and the ability to search within the books, across the collection, in order to find specific information.”

On this website you can find titles like: "Aunt Babette's Cook Book: Foreign and Domestic Receipts for the Household: A Valuable Collection of Receipts and Hints for the Housewife, Many of Which Are Not to be Found Elsewhere,” by Aunt Babette.

Also, “The House Servant's Directory, Or A Monitor For Private Families: Comprising Hints On The Arrangement And Performance Of Servants' Work… And Upwards Of 100 Various And Useful Receipts, Chiefly Compiled For The Use Of House Servants,” by Robert Roberts.

Another fun website: “Old and Interesting,” specializing in the “history of domestic paraphernalia,” for example: nutcrackers: http://www.oldandinteresting.com/nutcrackers.aspx

And, mattresses: http://www.oldandinteresting.com/straw-mattresses.aspx

“We used always to think that the most luxurious and refreshing bed is that which prevails universally in Italy, which consists of an absolute pile of mattresses, filled with the elastic spathe of Indian corn; we mean that delicate blade from which the large head of the plant bursts forth. These beds have the advantage of being soft as well as elastic, and we have always found the sleep enjoyed on them to be peculiarly sound and restorative; but the beds made of beech leaves are really no whit behind them in these qualities, while the fragrant smell of green tea, which the leaves retain, is most gratifying. The only objection to them is, the slight crackling noise which they occasion when a person turns in bed...
Sir Thomas Lauder, quoted in Webster's Encyclopædia of Domestic Economy, c1844.”

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WARNING: Do not read the following section if you are squeamish or uninterested in nitty gritty gut flora ideas...

Otherwise, read on, for some information about Fecal Transplants--otherwise more delicately termed “fecal bacteriotherapy.” http://www.jinipatelthompson.com/phpBB3/topic309.html .

"...Reconstitution of the gut flora by exogenous administration of probiotics offers the potential to prevent and possibly treat infection. Such an approach has traditionally involved oral administration of limited species of bacteria or yeast. However, the ability of these organisms to colonize the colonic epithelium is variable and the specific complement of microorganisms required to prevent or treat infection is unclear.

"Data supporting a role for oral probiotics in gastrointestinal disease including C. difficile infection have been mixed. (See "Probiotics for gastrointestinal disease").

"An alternative approach involves administration of the entire fecal flora from a healthy individual, an approach referred to as fecal bacteriotherapy. Although the data are limited to case series, fecal bacteriotherapy has been used successfully to treat relapsing C. difficile infection and more recently for refractory inflammatory bowel disease [3] . Relapse of C. difficile occurs in 10 to 25 percent of patients treated with metronidazole or vancomycin. Furthermore, multiple relapses in the same patient are common, and up to 10 or more bouts of relapsing colitis have occurred in some patients...

"...The precise mechanisms for the benefits of fecal bacteriotherapy are unclear. However, the reappearance of Bacteroides species after treatment suggests that these organisms are involved in the restoration of the presumably antibiotic-damaged flora in the colon.

"...Colonization was associated with a correction of T cell deficiencies and TH1/Th2 imbalance and with appropriate elicitation of cytokine response essential for host protection. Bacteroides spp. predominated in studies involving quantitative stool culture also supporting their role in restoration of the stool flora [7,8] . Recurrent C. difficile infection resolved in six patients in a Scandinavian study following rectal instillation of a mixture of facultative aerobes and anaerobes, including several Bacteroides sub-species [5] . The pretreatment fecal flora was completely deficient in Bacteroides species, which were restored after intra-colonic infusions.

"EFFICACY: Case series have suggested clinical benefit of fecal bacteriotherapy in patients with severe or recurrent Clostridium difficile-associated diarrhea or recurrent C. difficile diarrhea who failed standard approaches [5,9-17] . The overall cure rate in patients treated with fecal retention enemas in our review of the literature (not yet published) was 80 percent (51/64). Patients often showed an immediate and complete resolution of diarrhea and associated symptoms and disappearance of the pseudomembrane. Repeated tests for the presence in stool of C. difficile and toxins became negative. Our experience (not yet published) has been similar to the published series; we have treated 61 patients of whom 55 (90 percent) achieved a prolonged cure.

"Efficacy appears to depend upon a number of factors including the freshness of donated stool, the frequency of enema administration, the use of lavage, and the repopulation of the entire colon [4] .

"Successful treatment with two or more fecal enemas was described in three reports (with a total of 23 patients) of pseudomembranous colitis refractory to antibiotic therapy or with multiple relapses [5,9,12,13] . In the largest series (16 patients with severe, refractory disease treated during an 18 year period), 13 patients responded dramatically with decreases in diarrhea, temperature and leukocytosis [12] . Three patients died but two did not have pseudomembranes at autopsy while the third had small bowel involvement. No adverse effects from the fecal enemas were noted.

"In another report of nine patients, a single administration of fecal enema (5-10 gm homogenized stool in pasteurized cow's milk) was effective in seven of nine patients, but the response (relief of diarrhea) was delayed for up to five days [16] . No relapse occurred during follow-up of 18 months..."