NEW CANADIAN STUDY: BREAST CANCER KILLS FEW WOMEN AFTER PROMPT TREATMENT.

this 5year Canadian followup  study of women after breast cancer confirms the recent (2008) follow-up from Italy about the low mortality from breast cancer detected and treated early (Elderly breast cancer patients treated by conservative surgery alone plus adjuvant tamoxifen: Fifteen-year results of a prospective study. Martelli G, et al National Cancer Institute, Milan, Italy.Cancer. 2008; 112; 3: 481-488).

In UK the annual deathrate for women from breast cancer was only 0.28% – but in the UK screening program, of 1.7million women screened, 4.8% were recalled for further screening – of whom only 80% had unnecessary screening- a giant burden to both patients and the NHS. Almost 80% fewer mammography procedures and facilities were actually required.

Contrary to the mythology and hype that breast cancer is a major killer of women, these three studies affirm that even in those who get breast cancer, it still kills only 0.5% a year of sufferers at any age, (as opposed to 1% of those over the age of 70yrs in the Italian study)
Thus >80% of truly asymptomatic women without good family history of breast cancer have the lucrative (to Industry) unnecessary regular screening mammography
– and there is no good evidence that in such women, (or men) regular repeat cancer screening makes any difference to survival..

The evidence from numerous sources is very strong, that appropriate supplements ie parenteral HRT (estrogen +testost- +progesterone -especially when combined with other natural biologicals eg – fish oil, coQ10, acetylcysteine, MSM, carnitine, arginine, ribose, herbs ; and minerals and vitamins) more than halve all major chronic degenerative diseases and premature deaths.

People who fear cancer and all disease , early disability – especially those with a significant family history- just have to use common sense:
– follow sensible diet and lifestyle including avoiding overweight, have bloodpressure and eye checks regularly,
– take a sensible combination of the >50 natural supplements (if only as a few oil capsules and a glass of powder blend twice a day, and either daily hormone cream (or a tiny
hormone subcut (self) injection every few weeks, or implant, or lowdose HT orally) ; and
– most important of all, report promptly to a doctor if they develop symptoms that do not settle in a few days eg unexplained pain bleeding, lumps or tenderness, swelling, breathlessness, cough, or change in vision, hearing or bowel or bladder habit etc; or persistent weight gain or loss.

If early and permanent supplements; and symptoms, are addressed early, the common major diseases rarely become major killers – we die active of healthy old age!. Without appropriate supplements including appropriate HRT even after breast cancer, all-cause disease and mortality is more than doubled. Waiting for sudden death, diabetes, obesity, blindness, hip fracture, cancer or dementia before starting safe lowcost permanent multi-prevention is truly crippling if not fatal.

Mission Statement On Appropriate Physiological Human Sex Hormone Replacement – Women And Men

Every week brings new conflicting headlines for and against sex hormone replacement for men and women. It is appropriate that this mission statement on HRT be repeated:

The “sex” in sex hormones may be a major distraction, since the major long term health issue about universal sex hormone decline with aging is not primarily about sexuality and hot flashes, but about ensuring a vibrant useful active independent second half of life (including sexuality) so that we die well – i.e. preventing the common major disabling aging diseases that rob us of decades of health.

It is about preventing the associated major risks of sudden death, or crippling diseases – obesity, diabetes, frailty, fractures, arthritis, heart attack, heart failure, stroke, visual and hearing loss, Parkinson’s, incontinence and dementia – and sexual impairment is sometimes the last complaint.

After insulin in 1922-3, human non-oral sex hormone replacement HRT was firmly established by 50 years ago by e.g. Schering AG and experts in USA, Canada, UK and Europe. Then Robert Wilson (Feminine Forever) and Industry introduced oral patent xeno – hormones (other non-human hormones -e.g. premarin and oral contraceptives- hormone therapy HT) “for women’s convenience” – and more profits.

Despite increasing warnings about cancer and thromboses with nonhuman especially oral hormones from the 1970s onwards, and sixty years of risk-free use of appropriate HT and especially balanced systemic Human sex hormones HuSH, the USA and Europe medical establishments then embarked determinedly in the 1990s with largely patent oral hormone therapy in the HERS, ESPRIT, Papworth, WHI, WISDOM, Oulu, HABITS and Stockholm trials – not just in early menopausal women, but especially in elderly women, those already at high risk of vascular disease and breast cancer. In elderly overweight women with established vascular and sub-clinical malignant disease, aggravation of these diseases especially with higher doses outweighed the reductions in fractures and colon cancer by such HT.

Up to WW2, there were few hormones, fast foods, TVs, cars or mechanical home / job aids, so most people were far more physically active and slimmer. Since then, technology has both extended life but also increasingly polluted it and reduced necessary exercise – with increasing obesity, feminization of nature , infertility, and consequently more diabetes, vascular disease – and sex hormone imbalance – in both men and women.

But, sixty years of use of physiological human hormone replacement – testosterone in men, estradiol – progesterone – testosterone; and appropriate conservative dose oral hormone therapy orally e.g. premarin + progestin in long term use – as in the Nurses Study, and the WHI and Oulu trials, in younger women – have shown reduced mortality and all aging major degenerative diseases without any significant adverse effects.

So even the world’s leading experts, even in the conservative strictly evidence-based International Menopause Society IMS and the International Society for Study of Aging Males ISSAM concur that there is no reason to withhold appropriate evidence-based HRT of the patient’s choice from hypogonadal men and women, since no individual modern chronic prescription designer drugs do as well.

No modern designer ie synthetic drugs do as well as the natural proven drugs- the supplements of minerals, vitamins and biologicals- including herbs, and many hormones and scores of other biologicals that decline with stress, disease and aging- in preventing, reversing all the common degenerative major diseases of aging. We can rarely completely reverse/ cure sudden death, dementia, stroke, heart failure, type 2 diabetes, cancer, blindness once these occur- but with the long-proven natural drugs that are abundantly and cheaply available, we can more than halve their occurrence , severity and thus disability.

comments and dialogue are welcome.

Cod Liver oil greatly reduces risky anti-inflammatory need.

This new study from the North Sea confirms what has long been common knowledge: that fish oil reduces- almost halves not just heart, mood, arrhythmia, diabetic and malignant disorders but also arthritis symptoms- and, longterm, premature mortality.

From the published studies, all that seems to matter is that reputable quality (cold-pressed) fish oil be used, and that the EPA+DHA (eicosapentanoic acid + docosahexanoic acid) dose be high enough- be it 1 or 3gms of the EPA-DHA a day. This core combination is close to 30% in average fish oil, and – within tolerance – more seems to be better.
Plant (omega 3/ 6 / 9 eg linoleic) oils should not be supplemented since these may neutralize some of the benefits of fish oil, apart from aggravating adiposity.

When combined early with appropriate vitamins, minerals, herbs eg cat’s claw, and other biologicals eg glucosamine-chondroitin and balanced parenteral human hormones, the need for corticosteroid, painkillers and synthetic anti-inflammatories seems to be much reduced- with enhanced safety.

There is no evidence from the published studies and experience that the patent ie designer non-steroidal anti-inflammatories are as good as let alone safer than cautious use of corticosteroids and glucosamine-chondroitin – which respectively slow if not reverse the course of the two major types of arthritis.

http://rheumatology.oxfordjournals.org/cgi/content/full/ken024v1 free full text
B. Galarraga, J. J. F. Belch ea, University of Dundee, Dundee, UK.
Rheumatology, March 24, 2008; (2008) ken024v1. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis

Dose-dependant side-effects limit the use of NSAIDs in the management of RA. T Double-blind placebo-controlled randomized study of 9 months’ duration. 97 patients with RA were randomized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or placebo capsules. At 12 weeks, patients were instructed to gradually reduce and if possible, stop their NSAID intake. Relative reduction of daily NSAID requirement after 9 months was the primary outcome measure.
Results. 58patients (60%) completed the study. Out of 49 patients 19 (39%) in the cod liver oil group and out of 48 patients 5 (10%) in the placebo group were able to reduce their daily NSAID requirement by >30% (P = 0.002, chi-squared test). No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed. Conclusions. This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients.

UPDATE: VITAMINS vs LACK OF EFFECTIVENESS OF MODERN DESIGNER DRUGS FOR DEMENTIA

LACK OF EFFECTIVENESS OF MODERN DESIGNER DRUGS FOR DEMENTIA. VIVA VITAMINS .

21 Sept 2014  update:  a new USA study Littlejohns, Llewellyn ea,  confirms  low Vitamin D  risk of dementia and Alzheimer disease.Neurology. 2014 Sep;83:920-8, that in 1658 USA elderly followed for ~5.6years, dementia more than doubled in those with baseline vit D level below 10ng/ml compared to those above 20ng/ml.

This confirmed the 2012 Angers study Annweiler Beauchet ea that the elderly with the highest  quintile of vitamin D intake had only 23% of the risk of AD of those in the lowest quintile.

So while there are numerous obvious reversible and avoidable causes for dementia, – syphilis, stroke, malnutrition   and poisoning known for millennia – on Pubmed vitamin D and dementia link  dates  back to 1968.  Vitamin D3 and  vitamin B12 supplements are two of the cheapest and safest to give since even a monthly or 3monthly shot – if not simply oral vit D3 orally fortnightly- can maintain good repletion, quality of life and longevity; while hugely reducing multisystemic diseases and infections. . .

Wikipedia still says soberly Currently, no medications have been shown to prevent or cure dementia.    By that they mean designer for-profit prescription drugs.

24 March 2008:  it took 8 authors (funded by the U.S. and Ontario Ministries of Health and McMaster University) 19 pages in a leading journal this month to show what has been obvious the past decade from Medline –
that the modern anti-dementia drugs produce clinically significant adverse effects but zero clinically meaningful benefit or remission/slowing of degenerative dementias.

This article highlighting the futility and irrelevance (as in arthritis; type 2 diabetes; osteoporosis; lipid- vascular disease, cancer) of modern designer drugs for prevention of everyday chronic degenerative aging diseases is truly POEM – Patient-Orientated Evidence that Matters

But does it need a massively costly study to show what has been obvious from every single published trial of these drugs?

Surely these anti-dementia drugs should be banned since their risks outweigh their benefits?
Talk about fiddling for a living.

Yet while appropriate long term sex hormone therapy the past >50 years for both sexes clearly lower (by perhaps 40%) the risk of dementia, fractures, vascular disease and all-cause premature deaths, with negligible risks, bureaucrats continue to insist that it must not be used longterm until major trials have proven it- which trials will never be done because these supplements are long out of patent.

One must ask again whether the bureaucratic bodies (professional associations, universities, Regulators, medical schemes, politicians) that strive to have effective safe supplements (HRT, vitamins, minerals, biologicals including fish oil, herbs) severely restricted – or made prescription only – are fearlessly independent of the massive financial inducements, lobbying power of the New Drug Industry on behalf of their wannabe substitutes for old supplements that work?

http://www.annals.org/cgi/content/full/148/5/379 Ann Intern Med. 2008 Mar 4;148:379-97.
Effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and memantine for treating dementia: evidence review for a clinical practice guideline. Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M. McMaster University, Hamilton, Ontario, Canada.

more bisphosphonate, statin complications:

note the latest designer drug complications-

severe diffuse pain from statins and biphosphonates,

interstitial lung disease, and tendon rupture, from statin:

FDA ALERT [1/7/2008]: ” FDA is highlighting the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates. Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics.”
read on at http://www.fda.gov/CDER/drug/InfoSheets/HCP/bisphosphonatesHCP.htm

CONCERNS ABOUT STATINS: COMPLICATIONS AND SIDE EFFECTS: TreatmentUpdate 150 Volume 17 Issue 4 2005 June/July http://www.catie.ca/tu.nsf/acdff2c60dab4741852571b60051c9fe/d5b21cf52ec5187785257066005ce726!OpenDocument Currently available statins include the following:
atorvastatin (Lipitor)
fluvastatin (Lescor and Lescor XL)
pravastatin (Pravachol)
rosuvastatin (Crestor)
simvastatin (Zocor)
“Statin safety controversy
The safety of statins has become controversial in recent years. In 2001, another powerful statin, cerivastatin (Baycol, Lipobay), had to be withdrawn from sale because, particularly at higher doses, it was linked to the development of muscle weakness and kidney damage. The manufacturer of cerivastatin, Bayer, was subsequently listed as a defendant in 14,700 lawsuits around the world. Nearly 3,000 of these have been settled at a cost of $1.3 billion US.

“Crestor was licensed in high-income countries over the past couple of years in this environment of lawsuits and heightened safety concerns. As a result, perhaps its side effects have come under more scrutiny than expected.

“An American consumer advocacy group, Public Citizen, has criticized regulatory authorities in that country for the approval of Crestor. Moreover, Public Citizen has asked the Food and Drug Administration (FDA) to ban the sale of Crestor because of concerns about its safety. However, the FDA has refused to do so.

Warnings from regulatory agencies
In 2004, several regulatory agencies in Canada and the European Union sent letters to physicians warning them to begin therapy with Crestor at a low dose of the drug and reminding them about possible side effects. Last year, Canada’s Federal Health Ministry also sent an advisory to patients asking them to review the use of Crestor with their doctors. In July 2005, Health Canada has issued yet another advisory to patients related to the use of statins, warning them about health conditions that may make users more susceptible to side effects from statins (a report on this appears later in this issue of TreatmentUpdate).
http://www.arc.org.uk/news/article/18492474 Statin use linked to tendon complications. Statins, popularly prescribed treatments for lowering cholesterol, have been linked to tendon complications, according to a new study published in the journal Arthritis Care & Research.

A team of French scientists found that although very rare, there was evidence of a link between statins, which are widely used and have been demonstrated to be safe in large clinical trials, and musculoskeletal complications, such as tendon impairment.

Studying patient records from the Rouen University Hospital database between 1990 and 2005, 4,597 side effects were associated with statins, most of which were extremely mild.

Approximately two per cent of these, identified in 96 cases, were attributed to tendon complications. Symptoms usually occurred within eight months of beginning statin therapy and included tendonitis and occasionally ruptured tendons.

“Our study suggests that regular tendinous clinical examination may be required in statin-treated patients, particularly during the first year following statin therapy initiation,” the authors reported.

Although the researchers did not know how statins are linked to tendon injury, they suggested that blocking cholesterol synthesis could reduce the cholesterol content of tendon cell membranes, making them less stable.

Title MHRA: class side-effects of statins
Date Published 04/02/2008 http://www.nelm.nhs.uk/Record%20Viewing/vR.aspx?id=589805
Reporter initials Nicola Pocock Hospital Pharmacist
Source MHRA Drug Safety Update; February 2008
” The February 2008 issue of ‘Drug Safety Update’ from the MHRA notes that product information for statins is being updated to reflect a number of different side-effects which appear to be a class-effect of these medicines. The following prescribing advice is given:

• Patients should be made aware that treatment with any statin may sometimes be associated with depression, sleep disturbances, memory loss, and sexual dysfunction

• Statins may very rarely be associated with interstitial lung disease. Patients should seek help from their doctor if they develop presenting features of interstitial lung disease such as dyspnoea, non-productive cough, and deterioration in general health (e.g., fatigue, weight loss, and fever)”

note: the MHRA list convenently ignores the insidious muscle damage- myopathy- kidney- liver damage that statins cause”.

These heavily prescribed drugs are never needed for mild-to-moderate lipidemia, or for osteoporosis, since there are better safer natural long-proven drugs.
ndb

How to Survive a Heart Attack When Alone: coughing and deep breathing? too little too late.

How to Survive a Heart Attack When Alone: coughing and deep breathing?
This email doing the rounds may be inappropriate advice that could cost people their lives. – see http://www.hoax-slayer.com/survive-heart-attack.html and http://www.viahealth.org/body_rochester.cfm?id=329

BUT an apparently reputable cardiologist (apparently ex Vietnam Medic) also recommends it: http://www.karinya.com/cpr.htm

BUT see the notes of caution at http://en.wikipedia.org/wiki/Cough_CPR.

In short, it may save those who have sudden arrhythmia- but it is less likely to save those who are having a huge heart attack.- for whom most interventions are too late. The compromise may be to switch on the vehicle’s emergency flicker, stop the car, start coughing while collapsing visible over the steering wheel with a hand on the hooter to attract attention..

Very very few people recover or survive well long term after spontaneous (ie non-violent, non-toxic) cardiac arrest outside hospital – the studies below from France, Germany , USA & UK indicate that successful survival without impairment is – in the best hands – below perhaps 5%. .

So only primary prevention pays. Fish oil halves sudden death; metformin halves the deathrate in type 2 diabetics – and halves new diabetes in the overweight; appropriate estrogen replacement lowers allcause premature mortality by a third; deficiency of testosterone, estradiol, minerals, vitamins, CoQ10 , arginine, carnitine and ribose play a crucial role in the development and reversibility of arrhythmia, cardio/vascular and all-cause degenerative disease; and testosterone is antiarrhythmic but estrogen arrhythmogenic.

By contrast, unlike the above proven life-extenders, no modern designer drugs for chronic use have been shown to significantly reduce all major chronic degenerative diseases and premature all-cause mortality.

Thus all should take natural supplements early and permanently – appropriate vigorous supplements of minerals, vitamins and biologicals (including fish oil, insulin sensitizers and sex hormone replacement), to minimize early vascular disease and arrhythmia potential.

ndb

Heart. 2007 ;93:601-5. Sudden arrhythmic death syndrome SADS : a national survey of sudden unexplained cardiac death.Behr ER, Casey A, Sheppard M, University of London, UK. The estimated mortality from SADS was 0.16/100 000 per annum (95% CI 0.12 to 0.21), compared with an official mortality of 0.10/100 000 per annum for International Classification of Diseases 798.1 (sudden death, cause unknown-instantaneous death) or 1.34/100 000 per annum for unascertained causes of death. CONCLUSIONS: Deaths from SADS occur predominantly in young males. When compared with official mortality, the incidence of SADS may be up to eight times higher than estimated: more than 500 potential SADS cases per annum in England. Families with SADS carry genetic cardiac disease, placing them at risk of further sudden deaths. SADS should therefore be a certifiable cause of death prompting specialised cardiological evaluation of families.

European Heart Journal 2006 27:406-412 Post-discharge survival following pre-hospital cardiopulmonary arrest due to cardiac aetiology: temporal trends and impact of changes in clinical management Jill P. Pell ea University of Glasgow,
The Heartstart Register was used to identify all 1659 patients discharged alive from Scottish hospitals during 1991–01 following pre-hospital arrest due to cardiac aetiology. Over the period studied, the proportion of people suffering pre-hospital arrest who survived to discharge from hospital changed from 11.6% (552/4766) in 1991–93, to 7.0% (558/8006) in 1997–01.

Resuscitation. 2005 65:49-55. Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale. Pfeifer R, ea University of Jena, Germany.
BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest are at risk of subsequent death or poor neurological outcome up to a persistent vegetative state. We investigated the prognostic value of several epidemiological and clinical markers in 97 patients undergoing cardiopulmonary resuscitation (CPR) after non-traumatic cardiac arrest between 1998 and 2002. RESULTS: 72.% of the patients died or remained in a persistent vegetative state; and 28.8% survived with severe, moderate or without neurological disorders. .

N Engl J Med. 1999 341(8):569-75. A comparison of standard cardiopulmonary resuscitation and active compression-decompression resuscitation for out-of-hospital cardiac arrest. French Active Compression-Decompression Cardiopulmonary Resuscitation Study Group.Plaisance P, ea .Lariboisière University Hospital, Paris, France. BACKGROUND: We previously observed that short-term survival after out-of-hospital cardiac arrest was greater with active compression-decompression cardiopulmonary resuscitation (CPR) than with standard CPR. In the current study, we assessed the effects of the active compression-decompression method on one-year survival. METHODS: Patients who had cardiac arrest in France, more than 80 percent of whom had asystole, were assigned to receive either standard CPR (377 patients) or active compression-decompression CPR (373 patients) according to whether their arrest occurred on an even or odd day of the month, respectively. The primary end point was survival at one year. The rate of survival to hospital discharge without neurologic impairment and the neurologic outcome were secondary end points. RESULTS: Both the rate of hospital discharge without neurologic impairment (6 percent vs. 2 percent, P=0.01) and the one-year survival rate (5 percent vs. 2 percent, P=0.03) were significantly higher among patients who received active compression-decompression CPR than among those who received standard CPR.

Chest. 1994 ;106:872-9. Survival after in-hospital cardiopulmonary arrest of noncritically ill patients. A prospective study. Berger R, Kelley M. Veterans Affairs Medical Center, Lexington, KY 40511.
BACKGROUND: The rising healthcare costs and the ethical and economic implications of cardiopulmonary resuscitation (CPR) have generated interest in defining criteria to predict the appropriateness of CPR in specific patients. Age has been proposed as one such a criterion. METHODS: As part of a quality assurance program, all instances of CPR (code-500) at our VA Medical Center were prospectively studied over a period of 45 months. Only events in noncritical care hospital areas were included in this analysis. The CPR data were prospectively collected, and follow-up of initial survivors was continued until the end of the study period or until a patient died. RESULTS: Of a total of 422 code-500 events, 387 (92 percent) met our study definition of cardiorespiratory arrest, and 255 of these occurred in a noncritical care area and were included in the study. Our immediate survival was 52 percent (n = 132), survival after intensive care unit (ICU) stay was 22 percent (n = 55), survival to hospital discharge was 11 percent (n = 28), and 4 percent of the patients (n = 10) were alive at the end of follow-up (mean, 22 months). None of the patients discharged alive had a significant new neurologic deficit, and all but one returned to their preadmission environment. The post-CPR hospital charges for each of the surviving patients was estimated at $63,000. Whether in-hospital CPR in noncritical care areas is cost-effective is an issue that society at large must eventually decide.

Drugs Exp Clin Res. 1992;18:355-65. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Davini P, ea Santa Chiara Hospital,Pisa, Italy. A controlled study was carried out on 160 patients of both sexes (age between 39 and 86 years) discharged from the Cardiology Department of the Santa Chiara Hospital, Pisa, with a diagnosis of recent myocardial infarction. L-carnitine was randomly administered to 81 patients at an oral dose of g 4/die for 12 months, in addition to the pharmacological treatment generally used. For the whole period of 12 months, these patients showed, in comparison with the controls, an improvement in heart rate (p < 0.005), systolic arterial pressure (p < 0.005) and diastolic arterial pressure (NS); a decrease of anginal attacks (p < 0.005), of rhythm disorders (NS) and of clinical signs of impaired myocardial contractility (NS), and a clear improvement in the lipid pattern (p < 0.005). The above changes were accompanied by 90% lower mortality in the treated group (1.2%, p < 0.005), – in the control group mortality was 12.5%. Furthermore, in the control group there was a definite prevalence of deaths caused by reinfarction and sudden death. On the basis of these results, it is concluded that L-carnitine represents an effective treatment in post-infarction ischaemic cardiopathy, since it can improve the clinical evolution of this pathological condition as well as the patient’s quality of life and life expectancy.

Mol Aspects Med. 1994;15 Suppl:s165-75.
Usefulness of coenzyme Q10 in clinical cardiology: a long-term study.Langsjoen H, University of Texas Galveston .
Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes.. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented . Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.

Mol Aspects Med. 1994;15 Suppl:s143-7. Coenzyme Q10 and antioxidants in acute myocardial infarction.
Kuklinski B, ea Klinikum Südstadt, Rostock, Germany.
Sixty-one patients admitted with acute myocardial infarction, and a symptom’s duration of less than 6 hr were randomized into two groups. Immediately after hospitalisation, members of the verum group (n = 32) received 500 mcg of selenium (as sodium selenite). Thereafter they received a daily dosage of 100 mg coenzyme Q10 (Bio-Quinone) and 100 mcg selenium (seleno-methionine) for a period of one year. The control group (n = 29) were given matching placebo preparations.. Biochemical parameters showed a reduced concentration of CPK- and ASAT-level in the verum group during the acute phase (although not statistically significant). None of the patients in the verum group (i.e. on antioxidative treatment) showed prolongation of the frequency corrected QT-interval. In the control group, 40% revealed a prolongation of the QT-interval by more than 440 msec (p < 0.001). There were no significant differences, with respect to early complications. During the one-year follow-up period after myocardial infarction, six patients (20%) from the control group died from re-infarction whereas one patient from the verum group suffered a non-cardiac death.

Int J Tissue React. 1990;12(3):163-8. Pronounced increase of survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy. Langsjoen PH, ea Scott and White Clinic, Temple, TX USA.
During 1982-86, 43/137 patients with cardiomyopathy, Classes II, III and IV, had ejection fractions (EF) below 40%, and a mean EF of 25.1 +/- 10.3%. During treatment of these 43 patients with coenzyme Q10 (CoQ10), EF increased to 41.6 +/- 14.3% (p less than 0.001) over a mean period of 3 months (range, 2-4 months). The mean CoQ10 control blood level was 0.85 +/- 0.26 micrograms/ml which increased on treatment to 1.7 to 2.3 micrograms/ml for five periods up to 36 months (each period, p less than 0.001). The survival rates for all 137 patients treated with CoQ10 and for the 43 patients with EF below 40% were both about 75%/46 months. These two survival rates were comparable between 24 and 46 months, which is of extraordinary significance and importance when compared to survival of about 25%/36 months for 182 patients with EF below 46% on conventional therapy without CoQ10. The improved cardiac function and trippled survival show that therapy with CoQ10 is remarkably beneficial due to correction of CoQ10 deficiency in mechanisms of bioenergetics

Pioneering Midwife Touts Orgasmic birthing

Dr Joe Mercola gives praise where it is due:

http://articles.mercola.com:80/sites/articles/archive/2008/3/13/pioneering-midwife-touts-quot-orgasmic-birth-quot.aspx

Latest Endocrine news from JCEM

oral contraceptives & progestin are bad news.
Metformin needs to be started pre teens in overweight kids.
50% of Diabetic men have testosterone deficiency

Selected Abstracts

Evidence for Insulin Suppression of Baseline Luteinizing Hormone in Women with Polycystic Ovarian Syndrome and Normal Women Mark A. Lawson*, Sonia Jain, R. Jeffrey Chang ea University of California, San Diego,

Context: In PCOS women the relationship of insulin to LH secretion and responses to GnRH remains unresolved. A rigorous analytical examination of this relationship has not been performed.

Objective: To determine the relationship of basal LH secretion and responses to GnRH, insulin and other endocrine variables in normal and PCOS women.

Design: In PCOS and normal women, mean composite 12 h LH secretion was analyzed for correlating factors. LH responses to varying doses of GnRH during a fixed rate of insulin infusion and LH responses to a fixed dose of GnRH during varying doses of insulin infusion were analyzed for contributing factors.

Setting: General Clinical Research Center, University of California, San Diego

Patients: 18 PCOS and 21 normal women underwent studies of frequent blood sampling and GnRH stimulation before and during insulin infusion.

Main outcome measures: Group mean composite 12h LH levels were assessed with respect to other endocrine variables. In addition, LH responses to GnRH with or without insulin infusion were assessed.

Results: In normal women, insulin negatively predicted mean LH. In PCOS, the combined effect of BMI (negative) and testosterone (positive) predicted LH. The best predictor of LH was BMI and insulin combined. Basal LH and LH responses to GnRH were unaltered by insulin infusion in normal women. These measures were reduced during insulin infusion in PCOS women.

Conclusions: In PCOS, insulin infusion suppresses pituitary response to GnRH. In normal women, insulin negatively correlates with mean LH and suppresses GnRH response at a high infusion rate.

Accuracy of Diagnostic Tests for Cushing’s Syndrome. A Systematic Review and Meta-analyses
Mohamed B. Elamin Victor M. Montori ea Mayo Clinic,

Context: The diagnosis of Cushing’s syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy.
Objective: To summarize evidence on the accuracy of common tests for diagnosing CS.

Data synthesis: We found 27 eligible studies, with a high prevalence (794 (9.2%) of 8631 patients had CS) and severity of CS. The tests had similar accuracy: UFC (n=14 studies, LR+ 10.6, CI 5.5, 20.5; LR- 0.16, CI 0.08, 0.33), salivary MC (n=4, LR+ 8.8, CI 3.5, 21.8; LR- 0.07, CI 0, 1.2), and the 1-mg overnight DST (n=14, LR+ 16.4, CI 9.3, 28.8; LR- 0.06, CI 0.03, 0.14). Combined testing strategies (e.g., a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n=3, LR+ 15.4, CI 0.7, 358; LR- 0.11, CI 0.007, 1.57).

Conclusions: Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.

Effect of Low Dose Oral Contraceptives on Metabolic Risk Factors in African-American Women
Barbara A. Frempong, Anne E. Sumner* ea National Institutes of Health, Bethesda,

Context: Effect of OCP-use on cardiovascular risk in African-American women is unknown.

Objective: To examine in African-American women, the effect of OCP-use on insulin resistance, glucose intolerance and triglycerides (TG). Design: Cross-sectional study

Setting: Study was conducted at the National Institutes of Health Clinical Research Center

Participants: One-hundred-four healthy non-diabetic African-American women (21 OCP-users, 83 controls, age mean±SD, 34.7±7.6years, BMI 31±8.4kg/m2)

Interventions: Subjects had oral glucose tolerance tests (OGTT), insulin modified-frequently sampled intravenous glucose tolerance tests and fasting lipid profiles. Insulin resistance was determined by the insulin sensitivity index (SI).

Main Outcome Measures: Insulin resistance, glucose tolerance status and TG levels.

Results: Fasting glucose did not differ between OCP-users and controls (P=0.27). In contrast, compared to controls, 2-hour glucose (135±23 vs.120±25 mg/dL, P=0.01) and fasting TG (73 ±31 vs.57 ±27 mg/dL, P=0.02) were higher in OCP-users. OCP-users tended to be more insulin resistant than controls (SI: 2.51±2.01 vs. 3.46±2.09, P=0.09). Multiple regression analysis revealed that BMI, age and OCP-use were significant determinants of 2-hour glucose (adjR2=0.37; P<0.001) and TG levels (adjR2=0.21; P<0.001). As BMI was a determinant of both 2-hour glucose and TG, participants were divided into non-obese and obese groups and the analyses repeated. Among the non-obese women, the OCP-users were more insulin resistant (SI: 2.91±1.58 vs. 4.35±1.88, P=0.03) and had higher prevalence of glucose intolerance than controls (OR 5.7; 95% CI 1.4–24, P=0.01).

Conclusion: In African-American women OCP-use is associated with increase in markers of cardiovascular risk manifested by increased insulin resistance, glucose intolerance and elevated triglycerides.

Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women
Jennifer S. Lee*, ea Steven R. Cummings University of California, Washington; Ohio, Harvard, Alabama-Birmingham School of Medicine;

Context: Endogenous estradiol, testosterone, and sex hormone-binding globulin (SHBG) may influence the risk of hip fracture.

Design and Methods: From the Women’s Health Initiative Observational Study, 39,793 eligible postmenopausal women did not have a previous hip fracture and were not using estrogen or other bone-active therapies. Of these, 400 who had a first-time non-pathological hip fracture (median follow up=7 years) were matched to 400 controls by age, ethnicity, and baseline blood draw date. Estradiol, testosterone, and SHBG were measured in banked baseline serum.

Results: Compared with women in the lowest tertiles, those with bioavailable testosterone in the highest tertile had a lower risk (odds ratio, OR = 0.62; 95% CI: 0.44, 0.88); those with bioavailable estradiol in the highest tertile had a lower risk (OR = 0.44; 95% CI: 0.29, 0.66); and those with SHBG in the highest tertile had a higher risk (OR = 1.90; 95% CI: 1.31, 2.74) of hip fracture. In models with all three hormones and potential confounders, high SHBG remained a strong independent risk factor (OR = 1.76; 95% CI: 1.12, 2.78), high bioavailable testosterone remained protective (OR = 0.64; 95% CI: 0.40, 1.00), but estradiol no longer was associated (OR = 0.72; 95% CI: 0.42, 1.23).

Conclusions: High serum SHBG is associated with an increased risk of subsequent hip fracture and high endogenous testosterone with a decreased risk, independent of each other, serum estradiol concentration, and other putative risk factors. But endogenous estradiol has no independent association with hip fracture.

Changes over 14 Years in Androgenicity and Body Mass Index in a Bi-racial Cohort of Reproductive Age Women
Barbara Sternfeld* David S. Siscovick ea
Kaiser Permanente; & Unoversities of Northwestern Texas, Alabama,Minnesota, Washington,

Background: Body mass index is directly related to testosterone (total T and free T) and inversely to sex hormone binding globulin (SHBG) cross-sectionally, but little is known about how changes in body fat and androgen markers affect each other over time.

Methods: Participants included 969 white and black women from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, who were ages 18–30 at entry into the study and were pre- or peri-menopausal 16 years later at the time of the CARDIA Women’s Study (CWS). Total T and SHBG, were assayed from specimens drawn at the CWS examination and stored serum from the Years 2 and 10 CARDIA exams. Free T was calculated based on total T and SHBG. Body mass index (BMI) and waist circumference were measured at Years 2, 10 and 16.

Results: Despite clinically significant increases in BMI and waist circumference, total T and free T tended to decline while SHBG remained relatively constant. BMI and waist circumference were directly correlated with free T and inversely correlated with SHBG in cross-sectional analyses. In longitudinal, multivariable analyses, an annualized increase in BMI was inversely related to a concurrent annualized decrease in SHBG (beta = -0.79 ng/dl, s.e. = 0.22 in blacks; beta = -1.07 ng/dl, s.e. = 0.31 in whites). However, early increases in BMI were not related to later decreases in SHBG.

Conclusion: Increases in adiposity are closely tied to decreases in SHBG, but changes in body mass index and SHBG may occur concurrently rather than sequentially.

Low Testosterone Levels are Common and Associated with Insulin Resistance in Men with Diabetes
Mathis Grossmann George Jerums ea University of Melbourne,

Context: Low testosterone levels are common in men with type 2 diabetes and may be associated with insulin resistance.

Objective: We investigated prevalence of testosterone deficiency and the relationship between testosterone and insulin resistance in a large cohort of men with type 2 and type 1 diabetes.

Design: Cross-sectional survey of 580 men with type 2 diabetes and 69 men with type 1 diabetes. A subgroup of 262 men with type 2 diabetes was then reassessed after a median of six months.

Results: Forty-three percent of men with type 2 diabetes had a reduced total testosterone (TT), and 57% had a reduced calculated free testosterone (cFT). Only 7% of men with type 1 diabetes had low TT. By contrast, 20.3% of men with type 1 diabetes had low cFT, similar to that observed in type 2 diabetes (age-BMI adjusted odds ratio 1.4, 95% CI 0.7–2.9). Low testosterone levels were independently associated with insulin resistance in men with type 1 diabetes, as well as type 2 diabetes. Serial measurements also revealed an inverse relationship between changes in testosterone levels and insulin resistance.

Conclusions: Testosterone deficiency is common in men with diabetes, regardless of the type. Testosterone levels are partly influenced by insulin resistance, which may represent an important avenue for intervention, while the utility of testosterone replacement remains to be established in prospective trials.

Metformin Treatment for 4 yr to Reduce Total and Visceral Fat in Low-Birthweight Girls with Precocious Pubarche
Lourdes Ibáñez* ea University of Barcelona, University of Leuven,

Context and Objective: A low birthweight (LBW) tends to be followed by overweight, due to an excess of fat, including visceral fat. LBW girls with precocious pubarche (PP; pubic hair <8 yr) are at high risk for developing an adipose state of hyperinsulinemic androgen excess that leads towards early menarche. We explored the effects of insulin sensitization with metformin in LBW-PP girls.

Setting, Design, Patients, Intervention: Prepubertal LBW girls with PP [mean BW 2.4 Kg; age 7.9 yr; body mass index (BMI) 18.4 Kg/m2]; girls were randomly assigned to remain untreated (n=19) or to receive metformin for 4 yr (n=19; 425 mg/d for 2 yr, then 850 mg/d for 2 yr).

Main outcomes: at start and after 4 yr: height, weight; fasting insulin, glucose, IGF-I, testosterone, lipids, leptin, high-molecular weight (HMW)-adiponectin; body composition by absorptiometry; abdominal fat partitioning (only 4 yr) by magnetic resonance imaging; menarcheal status.

Results: Metformin-treated girls gained on average 5.5 Kg (or 50%) less fat, were after 4 yr less insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less atherogenic lipid profile, and were less likely to be post-menarcheal than untreated girls, while their gains in height, lean mass and bone mineral density were similar. After 4 yr, untreated girls had more visceral fat, a higher ratio of visceral-to-subcutaneous fat, and a higher leptin-to-HMW adiponectin ratio (all 50% higher) than metformin-treated girls.

Conclusion: Long-term metformin treatment appears to reduce total and visceral fat in LBW-PP girls, and to delay menarche without attenuating linear growth, thereby opening the perspective that adult height may be increased.

24-h Serum Levels of Growth Hormone, Prolactin and Cortisol in Pre- and Postmenopausal Women. The effect of combined estrogen and progestin treatment
Nea Kalleinen , Olli Polo ea Universities of Turku & Tampere. Finland

Objective: To study the 24-h profiles of growth hormone (GH), prolactin (PRL) and cortisol concentrations in older postmenopausal and in middle-aged premenopausal women, before and after estrogen-progestin treatment (EPT).

Design: A randomized, placebo-controlled trial. GH, PRL and cortisol were sampled every 20 min for 24 hours in 18 postmenopausal (aged 58–70 years) and 17 premenopausal (aged 45–51 years) women before and after six months of EPT.

Results: The mean 24-h GH (1.0 vs 1.8 mU/L, p = 0.033) and PRL (6.8 vs 10.0 ng/mL, p = 0.009) concentrations were lower in postmenopausal than in premenopausal women. After EPT the postmenopausal GH and PRL did not differ from premenopausal baseline levels. Postmenopausal mean 24-h GH (p < 0.001) and PRL (p = 0.002), daytime GH (p < 0.001) and nighttime PRL (p = 0.004) were higher during EPT compared to placebo. Cortisol levels did not differ. Premenopausal mean nighttime PRL (p = 0.026) and cortisol (p = 0.018) were higher during EPT compared to placebo. Postmenopausal PRL and premenopausal GH and PRL concentrations were higher at night than during the day. EPT did not alter this pattern.

Conclusions: Menopause was associated with decreased 24-h levels of GH and PRL, which were reversible with EPT. In contrast, cortisol levels were not affected by menopause or EPT. In middle-aged premenopausal women the studied effects of EPT were limited to nighttime increases of PRL and cortisol.

EFFECTS IN POSTMENOPAUSAL WOMEN OF ESTRADIOL AND MEDROXYPROGESTERONE ALONE AND COMBINED ON RESISTANCE ARTERY FUNCTION AND ENDOTHELIAL MORPHOLOGY AND MOVEMENT
Karolina Kublickiene Andrea R. Genazzani Tommaso Simoncini ea
Universities of Karolinska & Pisa,

Context: Endothelial dysfunction in resistance arteries after menopause is imortant for the development of high blood pressure and cardiovascular disease.

Objective: To study the effects of different hormone replacement therapies (HRT) on the function and morphology of isolated resistance arteries, and to look for their mechanistic basis.

Design and setting: A randomized, placebo-controlled double-blind study in a University hospital, along with laboratory-based studies.

Patients and interventions: We isolated resistance arteries in subcutaneous biopsies from 55 postmenopausal women before and after 3 months of therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 + MPA or placebo. In addition, we studied isolated human endothelial cells.

Main Outcome Measures and Results: Artery flow-mediated dilatation was augmented after treatment with E2 or E2+MPA, whereas MPA or placebo had no effect. Pressure-induced myogenic tone was reduced by E2 + MPA, while it was unchanged in the other groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs of endothelial apoptosis, but the addition of MPA impaired these events. E2, MPA or the combination all increased the expression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect.

Conclusions: This study suggests that HRT with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.

[

THE CRIMINAL BIPHOSPHONATE DECEPTION

BONE BOOSTERS? Biphosphonates BNPs NDB 2007 updated 19 March 2008; 6 April 2008

No trials have ever been published showing that biphosphonates do overall good long term for osteoporosis- ie reduce all-cause mortality, and reduce hip fracture, without toxicity.
Biphosphonate Osteonecrosis of long bones was already published in 1995, and from 2001 in USA.
So their heavy marketing, and prescription like vitamins, causing the epidemic of devastating osteonecrosis, makes the prescribers, manufacturers, dispensers and Regulators – eg the FDA -criminally liable.

Effects of continuing ALENDRONATE after 5 years of treatment: Fracture Intervention Extension to 10yrs
JAMA. 2006 Black, Cummings UCSF. (who funds them?!)
In 1099 women re-randomized to alendronate or placebo for a further 5 years (1998-2003):

Continuing alendronate halved only recognized vertebral fracture risk (2.4% vs 5.3% for placebo);

their conclusion: “women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years”. Ie no benefit for the far more important hip bones.

But was this a dangerous lie?
the 19% Risk of nonvertebral fractures was no different (RR 1 ) between continuing and discontinuing alendronate.

“Susan Ott (JCEM Mar 2005) already questioned bisphosphonate long term safety”

Biphosphonate BPN Jaw OSTEONECROSIS ONJ is now endemic worldwide:
1st reported in 1994 (Guanabens, Spain- leg stress #s),
2001-03 – USA 63 cases (Ruggiero 2004)
(2002-5 Pozi) Italy- 35 ;
(2003-5 (Abu-Id 2006) Germany 73 cases
2004-5 (Mavrotoki) Australia 158

by July 2006 over 3000 cases of ONJ were reputedly already reported.

“of Odvina‘s 9 cases of spontaneous fractures on alendronate –
5 were mid-femur fractures (2 bilateral same as Toulouse).
6 had delayed or absent fracture healing.

Estrogen alone is anabolic only on bone, uterus, memory, fat – If anything it both builds inner hostility, fattening, inflammation,
& wastes collagen ie muscle catabolic – thus doubles incontinence.

The only true anabolics (ie strengthen muscle, melt fat) are
* food incl vita-/minerals incl. vitamin C/D; CoQ10, carnitine,
* Insulin sensitizers – metformin; natural androgens, exercise.

Dach: “ Look at Toulouse Lautrec.. His parents were first cousins…
” we are giving women Toulouse Lautrec’s bone disease- the same jaw necrosis, mid-femur fractures, failure of bone healing,

“ But women who sustain fractures on BPNs are told that the fractures are due to the underlying osteoporosis, not the drug”
http://www.drdach.com/wst_page6.html

The osteonecrosis problem may be 95% with iv BPNs (Urade) – orally BNPs like HRT are absorbed below 10%;
but
as with oral HRT, the problem may be both total dose absorbed, and total length of exposure –BPNs (given over perhaps a year iv) bind to bone for 10yrs. Fosamax is swallowed for 3-5yrs.
Jones & Wilkinson’s (April 2006 NHS review of oral BPN adversity) found that adherence on oral BPNs is only around 50% by 3 years due to adversity – GIT, musculoskeletal, skin….
and when stopped, BMD is maintained for up to 2 yrs due to bound Testosterone (unlike estrogen).

Is there (as there was with tobacco, Premarin & Vioxx)
a BMD industry OSTEOPOROSIS FRACTURE DECEPTION?

The OSTEOPOROSIS FRACTURE DECEPTION?:

The chief risk factor for fractures is not BMD, osteoporosis,

but immobility, falls, inco-ordination, muscular frailty = sarcopenia
– which in turn limits exercise, endurance, motivation.

By contrast,
permanent appropriate TRT in men and T+ E2RT in women can prevent eg the up to 40% bone loss that occurs in 6 months on corticosteroids (Studd 1989),

restore up to 26% of lost BMD in critical areas like Ward’s triangle ie (the hipbone’s neck);

of the 6 published RCTs that have given testosterone replacement (with or without estrogen) for 1-2 years post menopause, 5 showed that testosterone gave better increase in BMD than estrogen alone.
In the 6th and oldest study (Studd 1992) in women both with and without hysterectomy, adding implants of testo 75mg 6mthly to Esto 100mg 6mthly made no difference over esto alone, possibly because the of the supraphysiological esto level attained (mean ~1.9nmol/L per Studd 2006) and the followup of only 1year.

In the 7th trial of only 6 months(2005), no improvement was seen in BMD on either esto alone or on Esto + testo- but it used oral HRT; lean mass increased only on the combination- so these women would have been less prone to falls and fractures. .

On the baker’s dozen of natural supplements, we have seen bone density increasing steadily by 1% a year – slightly faster in spine than hip- over 15 years in eg a severely osteoporotic woman with chronic active rheumatoid arthritis on prednisone.

After osteonecrosis the results with hyperbaric oxygen added to the natural supplements appear useful to justify it’s use to salvage whats left ..

HRT AND FRACTURES:

IN the Women’s Health Initiative,

the fracture rate in those with womb was 0.15%pa,
and E+P reduced this by 34% over 5.6yrs;

in those post hysterectomy ie longer without hormones,
the fracture rate was 0.17%pa,
and E alone reduced this by 39% ie 60% still had long bone fractures.

No trials have measured fracture rate on TRT in women;
but we never see women on TRT have spontaneous limb fracture.

Only androgen improves muscle strength;
HRT suppresses relative androgen levels.
so why must women go without replacement androgen?

ndb

Use of platelet-rich plasma in the management of oral biphosphonate-associated osteonecrosis of the jaw: a report of 2 cases. J Oral Implantol. 2007;33:371-82 Lee CY, ea
Bisphosphonates (BP) are nonhormonal medications used in the treatment of various bone malignancies and metabolic conditions. Since 2003, there have appeared a significant and growing number of articles in the worldwide medical and dental literature describing the complication of an osteonecrosis of the jaws associated with the intravenous and, most recently, the oral form of BP medication that has been refractory to any definitive form of treatment. The authors have successfully managed 2 patients taking the oral form of BP with adjunctive treatment using platelet-rich plasma (PRP), and in one case with hyperbaric oxygen (HBO). We were able to obtain complete remission in each case, which is defined as resolution of pain and complete closure of exposed bone in the jaws. The purpose of this report is to describe a treatment protocol and the rationale for using PRP and HBO to obtain complete remission of this new pathologic condition.

Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series.J Oral Maxillofac Surg. 2007 Jul;65(7):1275-6. Freiberger JJ, Padilla-Burgos R, Chhoeu AH, Kraft KH, Boneta O, Moon RE, Piantadosi CA.Duke University Medical Center, Divers Alert Network, Durham,.
PURPOSE: Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) is an emerging problem with few therapeutic options. Our pilot study of BP-ONJ investigated a possible role for hyperbaric oxygen (HBO(2)) therapy. PATIENTS AND METHODS: A total of 16 patients, ranging in age from 43 to 78 years, with BP-ONJ were treated with adjunctive HBO(2) between July 2003 and April 2006. Staging was based on the size and number of oral lesions. Clinical response after treatment and at distant follow-up; the odds of remission, stabilization, or relapse; and time to failure analysis were calculated. RESULTS: The median time on BP therapy before appearance of ONJ symptoms was 18 months, and that from symptom onset to HBO(2) therapy was 12 months. Fourteen of 16 patients (87.5%) improved in stage. The size and number of ONJ lesions were decreased after HBO(2) therapy (P < .001 and P = .008, respectively; Wilcoxon signed-rank test). Immediately after HBO(2) therapy, 7 of 16 patients (44%) were in remission and 8 (50%) had stabilized; however, stabilization without remission was sustained in only 2 patients. At follow-up, 10 of the patients (62.5%) were still in remission or had stabilized. The 7 patients who continued on BP treatment during HBO(2) therapy had a shorter time to failure (8.5 months; 95% confidence interval [CI] = 7.1 to 9.8) than those who discontinued the drug (20.1 months; 95% CI = 17.5 to 23.9; P = .006 by the log-rank test). Clinical response was not associated with cancer type or malignancy remission status. CONCLUSIONS: Adjunctive HBO(2) therapy may benefit patients with BP-ONJ; however, the outcome is improved with cessation of BP administration.

3: Am J Otolaryngol. 2007 May-Jun;28(3):158-63.
Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals.
Magopoulos C, Karakinaris G, Telioudis Z, Vahtsevanos K, Dimitrakopoulos I, Antoniadis K, Delaroudis S. Aristotle University, Thessaloniki, Greece.
PURPOSE: Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. In the last two and a half years, there has been a striking increased referral of patients with exposed necrotic jawbone, mostly after several teeth extractions. The only clinical feature common in all patients was the use of bisphosphonates in the treatment of bone diseases. PATIENTS AND METHODS: We performed a retrospective multicentric study of 60 patients with necrotic bone lesions of the jaws of various extent from July 2003 to October 2005. The necrotic bone involved the maxilla (37%), the mandible (50%), or both (13%). The bisphosphonate administered was mostly zoledronate. The management of the patients included cessation of bisphosphonate therapy for more than 6 months, long-term antibiotics, hyperbaric oxygen administration in some cases, and various surgical restorative procedures. RESULTS: The implementation of the treatment protocol in 7 patients so far lead to high cure rates, whereas surgical restoration of the defect without previous cessation of bisphosphonate therapy had discouraging results. CONCLUSIONS: Clinicians and dentists should have in mind this new complication of bisphosphonate administration to identify and treat osteonecrosis of the jaws.

METFORMIN AS PRIMARY PREVENTION OF OBESITY, DIABETES AND THE OTHER MAJOR COMMON DEGENERATIVE DISEASES OF AGING

This column (see below) has repeatedly pointed out that metformin (aet 1922), a plant derivative, is the only designer drug ever that has both been tested in a real longterm RCT – 20yrs (the UKPDS 1998)- and shown to halve both all-cause mortality in type 2 diabetics, and the incidence of new diabetics when used preventatively in those at risk at all ages with increasing body fat.

This has now been confirmed by a new analysis by Sally Salpeter’s prolific group – whose 2006 metanalysis showed almost as good results for appropriate HRT. Metformin is simply a variant of appropriate HRT, since metformin, like fish oil, and appropriate testosterone and estradiol replacement, is effectively a prohormone that reduces insulin resistance and thus allows insulin to work and glucose to be metabolised as energy by muscle (including the heart) and brain, instead of being accumulated as fat (triglyceride) everywhere.

But while metformin is the only ‘synthetic’ panacea ever invented that remotely matches fish oil, appropriate HRT and all the other natural therapeutic food micronutrients in combination, it should not be forgotten that there are scores  of natural insulin sensitizers listed on the internet; of which the freely available two dozen are easily combined into a potent lowcost combination that, with simple avoidance of sugar and cooked fats – at least halves all disease.

This makes the prescription metformin largely unnecessary- the combination just has to be used with discretion, and sensible regular meals , exercise and the routine supplements, to avoid causing hypoglcemia.

ndb

Am J Med. 2008 Feb;121(2):149-157.e2.
Meta-analysis: Metformin treatment in persons at risk for diabetes mellitus.
Sally Salpeter ea Santa Clara Valley Medical Center, CA USA.
PURPOSE: We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes. METHODS: We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. RESULTS: Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7–4.0), fasting glucose (-4.5%, CI, -6.0–3.0), fasting insulin (-14.4%, CI, -19.9–8.9), calculated insulin resistance (-22.6%, CI, -27.3–18.0), triglycerides (-5.3%, CI, -10.5–0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3–3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. CONCLUSION: Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.