It has always amazed me how the most incredibly toxic chemotherapy drugs (such as the very appropriately named 5-FU) are given to cancer patients using the archaic algorithm of body surface area to establish dose. Pharmacokinetics and in particular pharmacogenomics has been heralded for years as the potential “new” way of individuating drug treatment according to the unique drug disposition and metabolism characteristics of each patient…in order to reduce toxicity and increase efficacy. The simplest test is a single dose probe to establish C max and drug clearance kinetics. This kind of testing IS NEVER DONE (althougha pediatric leukemia drug pathway is tested in this sort of way) and as a result millions of cancer patients suffer outrageous toxic side effects unnecessarily when undergoing chemo with classical cytotoxic drugs. Now we actually have a published study making what is an incredibly obvious suggestion - check and see before infusing poison into the patient. Its hard to believe that such a study is being published in 2006, decades after 5-FU has been in use….and it will probably be decades more before such mind bogglingly obvious PK/PG testing becomes routine…oh well. And this is nothing remotely like running DNA microarrays to establish SNP (single nucleotide polymorphisms) of the relevant drug metabolizing enzymes- a procedure which is technologically feasible but light years from being implemented in current oncological practice.

Bocci, G., C. Barbara, et al. (2006). “A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity.” Clinical Pharmacology & Therapeutics 80(4): 384-395.
Background and ObjectivesDihydropyrimidine dehydrogenase (DPD) plays a key role in the catabolism of 5-fluorouracil (5-FU) to 5-fluoro-5,6-dihydrouracil (5-FDHU), and as such, an impairment of DPD has been recognized as an important factor for altered 5-FU and 5-FDHU pharmacokinetics, predisposing patients to the development of severe 5-FU-associated toxicity. Our objectives were to avoid severe 5-FU toxicities in patients with greatly impaired 5-FU and 5-FDHU pharmacokinetics after the administration of a reduced test dose of 5-FU and to investigate possible 5-FU or 5-FDHU pharmacokinetic parameters of the test dose related to the most common drug toxicities that affect patients after the first cycle of 5-FU chemotherapy.MethodsPharmacokinetics of 5-FU/5-FDHU and DPD activity in peripheral blood mononuclear cells (PBMCs) were examined in 188 gastrointestinal cancer patients given a test dose of 5-FU, 250 mg/m2, 2 weeks before starting the planned 5-FU treatment of 370 mg/m2 plus l-folinic acid, 100 mg/m2, for 5 days every 4 weeks. Drug levels were examined by HPLC, and toxicities were graded according to World Health Organization criteria.ResultsThe 5-FU test dose was well tolerated in all patients. Of 188 patients, 3 (1.6%) had marked alterations of 5-FU/5-FDHU pharmacokinetics (ie, 5-FU half-life [t1/2[beta]] >5 hours, 5-FU total body clearance [CLTB] -1 [middle dot] m-2, and 5-FDHU time to reach maximum plasma concentration [tmax] >=45 minutes); they were excluded from 5-FU treatments and treated with irinotecan, which was well tolerated. The plasma disposition of 5-FU in the remaining 185 patients revealed an area under the curve (AUC) of 3.73 +/- 2.18 h [middle dot] [mu]g/mL (mean +/- SD), maximum plasma concentration (Cmax) of 16.78 +/- 8.61 [mu]g/mL, and t1/2[beta] of 0.16 +/- 0.15 hour, whereas the CLTB was 65.67 +/- 31.86 L [middle dot] h-1 [middle dot] m-2. The 5-FDHU plasma profile showed a Cmax value of 3.64 +/- 1.94 [mu]g/mL, whereas the tmax value was 26.63 +/- 10.06 minutes, with an AUC value of 3.71 +/- 1.90 h [middle dot] [mu]g/mL. The PBMC DPD activity was 202.15 +/- 141.14 pmol 5-FDHU [middle dot] min-1 [middle dot] mg-1 protein (95% confidence interval, 165-239.3 pmol 5-FDHU [middle dot] min-1 [middle dot] mg-1 protein). A significant correlation between 5-FU AUC and 5-FDHU AUC was found (r = 0.5492, P r = 0.328, P = .0121) and 5-FDHU Cmax (r = 0.369, P = .0044) was found. Interestingly, no relationships between PBMC DPD activity and common toxicities were found, whereas 5-FDHU tmax values greater than 30 minutes were associated with the risk of moderate to severe neutropenia and diarrhea (P = .0323 and P = .0138, respectively; chi-square test).ConclusionsThis study suggests a successful approach for preventing severe or life-threatening toxicities in gastrointestinal cancer patients who are candidates for standard 5-FU treatment by analyzing the 5-FU and 5-FDHU pharmacokinetic parameters after the administration of a reduced 5-FU test dose.

…that which we call a rose…By any other name would smell as sweet.

The matter here is taxonomy of the echinacea genus (not a rose …but daisy does not have the same resonance)

The most recent issue of HerbalGram, the magazine of the ABC (American Botanical Council) carries a review article on Echinacea systematics (Integrating Recent Knowledge about the Genus Echinacea: Morphology, Molecular Systematics, Phytochemistry by John T. Arnason, PhD; Bernard R. Baum, PhD; Shannon E. Binns, PhD). Its an interesting piece because it uses a pluralistic approach to systematics (incorporating morphology, DNA, phytochemistry and ecology) to provide a detailed and comprehensive argument for reclassifying the entire genus Echinacea. Now of course, this is what botanists, or at least systematic botanists do for a living. That is hardly interesting per se. The interesting point is their detailed proposals in this case, are controversial in that they elevate purpurea to a sub genus and demote angustifolia to a variation within pallida. In effect, they take the 10 species of McGregor (1968) and turn them into but four.
The proposed reclassification of Echinacea species is clearly founded on research that surpasses in depth and breadth that available to McGregor. Although herbalists generally find taxonomic turf wars unhelpful, there is a real sense in which they do highlight the fact that the science of systematics is a cess pit of philosophical assumptions and unanswered questions…., such What is a kind? What is a species? What is an individual? What does it matter? If such questions do not pique the interest…and for many I suppose they may not….there is another important point for herbalists when dealing with the taxonomy of medicinals - which is what are the medicinal properties or capacities of the different species or variations. The actual plants themselves do not change (nor do their therapeutic capacities) when their binomial designation is modified. If taxonomic changes are proposed then we may be reminded of the philosophical fragility of classification, and as herbalists we may re-examine carefully our understanding of each plant as a medicinal in order to solidify its role in clinical practice as opposed to its shifting role in the chimerical taxonomic universe.

How distasteful then to read, in the same issue of HerbalGram, an editorial by Blumenthal & Urbatsch (the latter being author of the Echinacea monograph in Flora of N. America) questioning the proposed echinacea revisions, not because of the science, and definitely not because of the philosophy, nor raising the clinical properties aspect but rather because

“..the suggested revisions and reclassification of the genus Echinacea would obviously require an eventual relabelling of the commercial Echinacea products, a cost that will be of dubious value to the industry and which will no doubt produce added confusion to the consumer.” p80

A succinct statement of exactly whose rear-end HerbalGram has its head stuck inside.

Just in case you were thinking of giving your goldfish intraperitoneal implants of the phytoestrogenic beta -sitosterol, you may want to think again - unless you want the boy fishes to develop fatty gonads. Whew…saved in the nick of time….after all…fatty goldfish balls have been a major concern as we all know

Sharpe RL, Drolet M, Maclatchy DL Investigation of de novo cholesterol synthetic capacity in the gonads of goldfish (Carassius auratus) exposed to the phytosterol beta-sitosterol. Reprod Biol Endocrinol. 2006 Nov 21;4(1):60

ABSTRACT: Total and intra-mitochondrial gonadal cholesterol concentrations are decreased in fish exposed to the phytoestrogen beta-sitosterol (beta-sit). The present study examined the potential for beta-sit to disrupt de novo cholesterol synthesis in the gonads of goldfish exposed to 200 microgram/g beta-sit and 10 microgram/g 17beta-estradiol (E2; estrogenic control) by intra-peritoneal Silastic(R) implants for 21 days. The de novo cholesterol synthetic capacity was estimated by incubating gonadal tissue with 14C-acetate for a period of 18 hours, followed by chloroform/methanol lipid extraction and thin layer chromatography (TLC) lipid separation. Lipid classes were confirmed using infrared spectroscopy. Plasma testosterone (T) and total cholesterol concentration were measured and gonadosomatic index (GSI) was calculated. Plasma T was significantly reduced in male beta-sit-treated fish compared to control and E2-treated fish (p<0.001). 14C-Acetate incorporation into cholesterol and cholesterol esters was not significantly different among treatment groups for male and female fish, however, 14C-enrichment was higher than expected in both triglycerides (TG) and free fatty acids (FFA). FFA incorporation was significantly higher in male control fish than either beta-sit or E2 treatments (p=0.005). Plasma cholesterol concentration was significantly increased in the male beta-sit treatment group compared to controls (p=0.027). These results indicate gonadal de novo cholesterol biosynthetic capacity is not disrupted by beta-sit or E2 treatment in early recrudescing male or female goldfish, while plasma cholesterol and steroid concentrations are sensitive to beta-sit exposure.

Once again, the indefatigable Narendra Singh (half of the UDub team of Lai and Singh that has led much of the in vitro and in vivo research on artemisinin and cancer) have published a case history in the Journal of Integrative Cancer Therapeutics. Interestingly in this case, the patients typical macroadenoma symptoms resolved with the ART treatment, although the lesion was still visible on CT. For CNS lesions we too have recommended artemether (a more lipophilic artemsinin derivative) which theoretically has superior blood brain barrier traversing properties. Full text available temporarily at Sage Publications site…

Singh, N. P. and V. K. Panwar (2006). “Case report of a pituitary macroadenoma treated with artemether.” Integr Cancer Ther 5(4): 391-4.

Introduction: This report describes the case of a male patient with pituitary macroadenoma treated with the artemisinin analog artemether. Patient and METHODS: A 75 year-old male patient presented with vision, hearing, and locomotion-related problems. Artemether was administered orally to the patient over a period of 12 months. RESULTS: Although the tumor remained consistent in size, CT scan shows a reduction in its density, and clinically, the related symptoms and signs resolved significantly as therapy progressed. Discussion: Overall, the artemether treatment was beneficial in improving the patient’s quality of life. Artemether and other artemisinin analogs offer promise for cancer therapy.

Sage ICT linkout (pdf full text)

Paul Bergner quicklysnagged the pdf files from Google Book of their scanned versions of several of Scudder’s Eclectic texts before they were inexplicably removed by Google…
Here are additional temporary links to 3 of the pdfs … Its likely that herbal internet maven Henriette Kress will be finding a permanent home for these, possibly in a searchable format…but meanwhile here they are.

The Eclectic Practice of Medicine - 12th edition ~48 Mb

Specific Medications - 1870 ~ 7.7 Mb

The Principles of Medicine - 1892 ~ 20 Mb

In September at the Breitenbush Herbal Conference in Oregon, and again in October at the American Herbalist Guild Symposium in Boulder I gave a presentation on Bach’s discovery of the English Flower remedies.

The approach was a little unusual in focusing on Bach’s own process, and developed its argument based upon close textual readings of Bach’s own writings. I suggested that Bach’s system transcended the medical model, and that the remedies are transformational tools in the vajryana buddhist sense, and arguably Bach was the most spiritually developed healer of the 20th Century, more a mystic than a medicine man.

A slide shown in Keynote by Apple (made famous by Al Gore) was appreciated by some audience participants. This requested upload is an MPEG movie of the keynote slides but without audio. You can get the audio from Living Tree, or else it will be posted here as soon as I get my grubby hands on the MP3 file. That file will be podcasted - this one is a straight download from the link below. I did an iPod optimized version (smaller file) but on my 80g video iPod it was illegible - so this is a big video file - 41 Mb - be warned, but at least it shows the nifty Keynote builds and transitions.

fast broadband best for download….
Bach Keynote Movie

There is an increasing, if tedious, tendency in mainstream literature to conduct surveys or polls of herb use “out there”. (wherever that is - a relevant point as we shall see) The findings are invariably the same - firstly that lots of people of all sorts of demographics and situations from pediatric to geriatric are taking herbs for everything from colds to cancer. The second main finding is invariably that most people taking herbs do not “disclose” the fact to their physicians! Duh. At this point the researchers usually lapse into a predictable standard litany about how terrible it is that herbs are unregulated, how herbs can cause dangerous interactions with drugs, and because of the deceiptful non-disclosure behavior by patients - physicians must be hypervigilant about the “problem” of herb use. A typical current example from Dr David Eisenberg’s Division for Research and Education in Complementary and Integrative Medical Therapies, Harvard Medical School, was recently published in Archives of Internal Medicine. (Gardiner P, Graham RE, Legedza AT, Eisenberg DM, Phillips RS Factors associated with dietary supplement use among prescription medication users. Arch Intern Med. 2006 Oct 9;166(18):1968-74) Eisenberg is of course the grandfather of surveys on CAM, and it appears that his department is set to continue to waste grant money on this kind of stuff….

The interesting point about these surveys is that none of them are able to actually describe the signifcance of their own findings. This is not because of some methodological defect in the survey instruments etc - the issue is quite fundamental. A survey of herb-use is simply not capable of knowing the experience of the subject being “surveyed”. What surveys of this kind repeatedly reveal is a major seismic shift, a structural pattern of popular behavior that implies that millions of people experience the limitations of standard practice biomedicine and have some intuitive grasp of the fact that using herbs may be a profoundly more appropriate approach to their wellness and/or ill health than that offered by their physicians and pharmaceutical drugs. People are taking herbs not because they are deluded, and the reason they do not disclose herb use to their doctors is obvious doctors don’t get it, because just like Eisenberg and his co-researchers  they can’t get it … so they keep on doing surveys. But since there is only a tiny number of practising herbalists, naturopathic physicians or other “CAM providers” out there to pervert the huge population involved we are looking at a huge demographic shift from “below”. The shift implies a change in consciousness - this cannot be grasped by any “survey methodology” - even if it a survey attempted an external description (which they usually do not) of the subjective factors involved it would just be an external description. The real significance of such a shift is that a novel intelligence is emerging in our society that anticipates the possibility of a deeper more profound conception of medicine, one whose values and therapeutics are in alignment with a more developed human-nature-centric world view. The anticipation of possibility is the precondition of its manifesting.

That is the good news about herb-use surveys.

Put that in your pipe and smoke it Dr Eisenberg - preferably before your next survey.

(more…)

A friend of mine here who has been having a bad time psychologically for a while was just Dx’d as bipolar and has been prescribed lithium. Funnily enough, Ashland Oregon, my hometown, is well known for its lithium-rich spring water, the local park here is even named Lithia Park. Tastes awful of course. But whatever one thinks about pharmacotherapy for so-called psychiatric diagoses according to DSM-IV etc, lithium continues to be Rx’d for this DSM “condition”. Maybe it will help my pal get through his bad patch.

Rather than talk about herbs for bipolar, how about herbs to prevent lithium-induced toxicities? Not dissimilar from using herbs to counteract the adverse effects of cancer chemotherapy. Hardly one’s favorite use of botanicals, but a herbalist has to do what a herbalist has to do…here is my protocol to counteract the primary toxcities (renal, thyroid and to some extent pulmonary) of lithium chronically administered.This is really what herb-drug interactions is all about…if anyone has any better suggestions let me know.

Tincture: Ginkgo FE, Cordyceps, Dan Shen, Urtica semen, Parietaria a/a 5 mL bid
Supplements: N-Acetyl cysteine, EPA, liposomal Milk thistle, + mixed dietary antioxidants (ACE-selenium I use Tyler’s version)