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Renal denervation lowers blood pressure independently of drugs

MD-FM Thursday December 27, 2012




GENERIQUE
Carillon
 

P1

PETER:
Hello. I’m Peter Goodwin with your special Christmas edition of MD-FM. I’ll be taking a reflective look at some of the medical developments this year.

PETER:
One that caught my imagination was a drug-free way of controling refractory hypertension!  At the European Society of Cardiology meeting in Munich, Murray Esler told us all about his group’s study of renal artery denervation done in his town of Melbourne, Australia:

Bob-Murray Esler:
 “Patients with essential hypertension often have very high tone in their renal sympathetic nerves and the procedure uses a device, a catheter, that emits radio frequency energy — that’s radio waves — into the lumen, or the central cavity, of both kidney arteries and the nerves go to the kidneys in the wall of the renal arteries, so the nerves get a dose of energy from this and they are silenced permanently.”
“So what are your 18 month results? What are your findings?”
“In the initially denervated group the BP fall of 32 on 12 is totally and perfectly sustained through to 18 months — exactly the same mean BP fall.  In the crossover group — with denervation followed out to 18 months — their pressure fall is now 28 systolic”
“What are the results on safety?”
“The safety of the device exceeded my expectations.  With putting a catheter into a renal artery there’s a low risk of some procedural errors; and one of these was in one patient the catheter was put into the wall of the renal artery — that’s called a renal artery dissection — and that patient needed a renal artery stent to keep the kidney artery open.  In terms of other safety: excellent, there’s no damage to renal function we’ve identified no narrowing of the renal artery from damage, so almost a clean slate for safety”
“What happened to medications?  These were originally extensively medicated weren’t they?”  
“The patients are on an average of five different bp lowering classes. In the initial phase of the trial we didn’t want to change that because we wanted to look at the denervation effect alone, and not the medication change. But it should be said that this is not a cure for hypertension: the BP is substantially lowered but most patients remain on some tabs. In some it is one of two less than they were on before, but typically there’s a good outcome on perhaps two tabs less than before”
“So what’s the very brief bottom line at the moment?”
“The brief bottom line is that we have a new way of treating hypertension and specifically drug resistant patients who have nowhere else to go. The efficacy is at a high level and the safety looks good.”

PETER:
That was Murray Esler Director of the Baker Institute in Melbourne talking about his findings from the SIMPLICITY study

P2

PETER:
For me one of the exciting stories of 2012 was in chronic myeloid leukemia.  The revolution from having imatinib to switch-off the disease process has been magnificent, and second-line tyrosine kinase inhibitors like nilotinib and dasatinib have continued the good work. But one molecular mutation — T 315 I — has, until now, still been keeping some patients resistant to these wonder drugs.  But at the American Society of Hematology meeting in Atlanta, Jorge Cortes, told me they’ve finally beaten even this. How did they do it?

bob-Jorge Cortes:
“Well we gave this drug, called ponatinib — it’s an oral drug — and we gave it to patients with CML in all stages, chronic, accelerated or blast phase, whether they had the T 315 I mutation or not – we gave it also to the other patients”
“But they were  resistant or refractory?”
“Absolutely.” They were all resistant to dasatinib or nilotinib actually most of these patients had already received all three TKIs and we found some outstanding results. The response rate was very, very, high.  In the chronic phase, for example, two thirds of the patients have achieved some cytogenetic response; and it’s been complete in almost half of the patients. And again — thinking that all of these patients had failed three TKIs, that’s outstanding!”
“What about side effects of this drug?”
The drug is very well tolerated. We know that all of these tyrosine kinase inhibitors have some side effects but they tend to be very minimal.  With ponatinib we have, for example, a little bit of a rash and dry skin in some patients — but usually very manageable. We have some head-aches. The one side effect of concern the in phase one [study] at the highest doses was pancreatitis. With the dose that we’re using now the incidence of pancreatitis now is much lower: it’s about six per cent of patients who have grade three pancreatitis — it’s usually manageable you adjust the doses and most patients can restart therapy so it’s something we can really manage in the clinic”
“So what would then be the correct way to approach any patient with chronic myeloid leukaemia from now on — bearing in mind that you have these different generations of TKIs?”
“Well I think the important steps start at the very beginning. I think that we have very good treatments — imatinib,  and now we’re going to the second generation drugs as initial therapy and they give us outstanding results, better responses, deeper responses, faster responses and I think that proper monitoring: if you follow your patients properly, if you make sure you minimize treatment interruption and dose reductions that are not needed — and all that — I think that the overwhelming majority or patients will not die of this disease.  There’s always going to be an occasional patient, but I think that – and here I think that the compromise is even higher for the physician —  is that if you do a good job for your patient I think that very few of these patients should die of CML.”
“So have you achieved it, have you: converted CML into a form of diabetes, but for cancer?”
“I think we have. I think that I have a large number of patients in the clinic – I follow probably more than 700 or 800 patients with CML — I have some of these patients that I’ve been following for more than ten years. I know their families. I know everything. And these people lead normal lives, they do their jobs, they do their exercise, they do the normal lives”
 
PETER:
Dr Jorge Cortes, Deputy Chair of the Department of Leukemia at the MD Anderson Cancer Center in Houston Texas, and Director of the CML and AML programs there.

VIRGULE MUSICALE

P3

PETER:
At the end of the year it’s time to reflect on food and eating.  And I’ve been checking up on the latest research on dieting and weight reduction at London’s Imperial College.  Surprisingly, Professor Jimmy Bell there told me it’s time to stop “demonizing” fat!

Bob-Jimmy Bell:
“Fat is a very important organ essential for your life.  You cannot have optimal health without having fat in your body. So nobody should aim at minimizing fat to zero.  Trying to maintain your weight as the ultimate measure of health is the wrong thing to do.  You have to have physical activity as part of your lifestyle, and that physical activity should include a method that will reduce internal fat rather than maintain a set weight.”
“Right. So it’s not a simple story. Now dieting is an important aspect of this.  Most people are trying to eliminate calories — or reduce them as much as possibl: is that a simple story?”
“Again it’s not a straightforward story.  If you actually want to maximize the health benefit of a lifestyle you should include physical activity.  Dieting alone will not only lose fat, but also you lose part of your muscle mass.  So long term it’s been shown that dieting does not work. But if you include exercise within that lifestyle choice it will work.”
“What are the simple ways of expressing this?”
“Well the first thing that we have to think is that nobody goes to bed thin and wakes up fat – it’s a gradual thing.  And the same thing is that we should lose weight gradually we should change our lifestyle overall, not only just look at dieting and reducing calories but also increasing physical activity” ”





PETER:
Jimmy Bell Professor of Metabolic and Molecular Imaging at IC (my old college, by the way!)  
But what then is the Route to Obesity and how can we avoid it?  In the next office at Imperial College Dr Tony Goldstone gave me the benefit of his research on brain stimulation when volunteers looked at different types of food and had their brains monitored with functional MRI

Bob-Tony Goldstone:
“Of course obesity is just the endpoint.  We measure someone’s height and weight – or if we’re being more sophisticated we measure their fat using machines, or MRI machines, or impedance machines or dex machines; but that’s just the end point. That’s just where they’ve ended up. But the route they’ve got there can be quite varied, and I think part of the problem is that  we assume that everyone gets to the same point of being overweight through overeating through the same reason – lack of self control. That’s what the general public thinks. But I don’t think that’s a very fair analysis of the multitude of ways that we can get there.  So we can get there…. maybe some people crave high calorie foods more.  Some people maybe get less pleasure from high calorie food and have to eat more to get the same pleasure, some people maybe impulsive – less able to wait to get the food later on; some people may be compulsive i.e. they may be les able to stop repeating the same action.  Some people overeat when they’re stressed or emotionally upset and that may be another contributor”
“And can you tell me about some of the work you’ve done, because you’ve had people being exposed to certain stimuli. Are there things you can distill about this for everyday use?
“Well I think we’re certainly aware from our studies that fasting seems to increase the activity of the brain to high calorie foods within this reward network and we know from epidemiological studies that people who skip breakfast — so they go through a long period of fasting — actually tend to gain weight over the long term! So skipping meals may be detrimental to how the body responds to high calorie foods.  Other poeple have shown — in other studies — that if people have short sleep durations: so for example they force people to have only five hours sleep a night and then put them in a scanner in the morning and see how they respond to hi cal foods, they get greater activation in their brain to high calorie foods in this reward network if they had a short sleep duration. So getting a good night’s sleep is another very practical point to prevent and help manage obesity”

PETER:
Tony Goldstone Consultant Endocrinologist at the Metaboloic and Molecular Imaging Group of London’s Imperial College, with food for thought in this season of feasts.

VIRGULE MUSICALE
And that winds up our Christmas edition of MDFM.  We’ll be bringing you another special programme in a week’s time to celebrate New Year.  Until then from the MDFM team, and from me, Peter Goodwin, goodbye!
 
 
JINGLE FIN    

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