The waiting game

Some of you may know that we have had an anxious wait for the results of little big dog's visit to the Cardiologist. We suspected that his heart murmur was aortic stenosis, based on Dr B's experience of the human heart, but until Themba had a couple of episodes of syncope (fainting) this Spring, we had no idea if this was serious or not. 

Our very own 'droopy dawg'

Last week, Themba underwent a series of tests to determine the cause of his collapse. First, he had an ECG, then an echocardiogram, and lastly a 24hr Holter monitor. He is a most good-natured dog and took it all in his stride. The ECG didn't show anything alarming but the echocardiogram (a bit like an ultrasound) showed that his heart is impaired and that he has severe aortic stenosis (a narrowing of the main artery as it leaves the heart, filled with fresh oxygenated blood for the body). He is not (yet) in heart failure.  

The canine cardiologist (like a GP with specialist interest) wanted to rule out something awful called ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy); in humans the most common cause of unexpected sudden death in the young. She checked his pedigree and we were relieved to see that his line does not carry the gene for ARVC. The 24hr Holter monitor showed no arrhythmia's and we are reassured, but the prognosis is still poor. 

Themba with Holter monitor (under his T-shirt) and
Brin showing solidarity in a T-shirt of his own!

He is now taking beta blockers, to slow down his heart activity, but it is not a treatment; it is simply a means of protecting his welfare and making sure that he has a good quality of life. The vet has warned us that he will continue to decline. Many dogs with this diagnosis have a median survival of just 19 weeks following diagnosis. This is horrific for us to contemplate. We plan to repeat the echocardiogram in mid-July to better understand the rate of decline in his heart function.  

The really frightening aspect of this condition is that whilst we can control (much) of the mad Boxer bouncy activity, he is just as likely to collapse while chasing the neighbour's gardener as jumping up for the doorbell. And we feel we shouldn't restrict his activity, he should be free to have as much fun as possible. In fact, he seems to be coping very well with his dodgy ticker, probably because we have kept him lean and fit. He is still going for his jog in the morning, a little slower these days, and our lovely evening walks. He still enjoys playing ball, but rests a bit in between each throw. The heat of May was clearly a factor in his severe collapse, but I hope that we can have a period of stability and happiness.

In other news, the puncture wound on my finger is healing well, although I still have a haematoma under my nail, which we are rather dramatically referring to as the crush injury. The side-effects of the antibiotics and Tetanus injection have eased. I have had this reply from the A&E Matron: 

'Thank you for bringing this to my attention. I have spoken to both staff involved and it would appear that there was a miss-communication between the receptionist and the Senior Nurse that she spoke to. The receptionist implied to the nurse that you were enquiring about Rabies injection, to which she quite rightly advised that if bitten by a dog in this country there should not be the need for a rabies injection but that we should contact the Health Protection Agency for advice if you had been bitten outside the UK.

I would like to apologise for the inconvenience that this caused you and re-assure you that the clinical staff are trained and up to date with such matters.

I have relayed to the receptionist concerned that she should have booked you in to the department and allowed you to be triaged by the nurse rather than getting involved in clinical questioning.'

The rain continues in Shackleford. As of yesterday, we had already had double the average monthly rainfall for June, the third month in a row that expected rainfall has been way exceeded. Unfortunately, it's also quite cool and I fear for my veggies this week. The carrots look especially sad, but everything looks a bit soggy. And I had to release a dead mouse from the bait trap - yuck!

So, that's the waiting over, now to get on with having some fun. We're getting away to the New Forest in the next few weeks,  to a lovely dog-friendly hotel, and can't wait to tell you all about it.

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Little big dog

I wrote about Themba's story earlier in the year. This brave little dog has overcome so many challenges, and now it seems that his aortic stenosis is getting worse. The recent hot weather has made him more susceptible, and I have been horrified to see him collapse, lose continence, fit and froth, and at one point I even thought he had stopped breathing. I rubbed his chest with my knuckles and shouted 'Themba, can you hear me?' There was no response. I ran inside and brought the ice tray out to the garden where he had collapsed. I pushed ice cubes under his lips and started chest compressions, a la Vinnie Jones in 'Hard and Fast' hands-only CPR. He came round with a start, his tongue rolling about, his eyes wild. I know now that he wasn't in cardiac arrest, he had fainted and stopped breathing. It took him over an hour to recover so we lay together in the garden, with Brin, until he was OK to walk back to the house. He's just too heavy for me carry.

The irony is that MrB is a cardiologist. He sees this kind of condition in human patients all the time. He runs the cardiac resuscitation program, but he wasn't as home when Themba collapsed, and he couldn't be contacted by phone either, as he was dealing with an emergency at the hospital. We are used to that, and we cope very well.

Themba has a referral for a canine cardiologist. She will measure the gradient across the aortic stenosis. This will give us an indication of the severity of condition. We hope that beta-blockers will help to control his heart rate, and that this may prevent further collapses. We are restricting his exercise at the moment, although he is actually a very fit boy. I'll keep you posted.

And in the meantime, have a fantastic Diamond Jubilee weekend. You can catch up with the Greensand Way runners, running 108miles for charity, or pop along to the Godalming Jubilee Run and fun day* on Monday 4th June. I will be marshalling the run at the intersection outside The Charterhouse pub.

*Message from the organisers: The Fun run is now full. To prevent over crowding, the entry to the Fun Run is capped at 275. Please do not attempt to enter this event on the day if you have not already registered.

5k and 10k run: Online registration will close Sunday 20:00. There's absolutely no entry allowed on the day. So please enter before Sunday 20:00.

With almost 720 registered across the runs and family fun run it is important to arrive in good time and read this website or the emails you receive. Details of parking are below and the race day itinerary will be released soon.

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Understanding the importance of statins

If you search for statin and cancer on the public science and medicine database and you will find 1,774 articles going back to 1976, so why was there a headline splashed across the newspaper last week? It’s not like we don’t already know about statins. Statins are taken by millions of people around the world to reduce cholesterol by blocking the mevalonate pathway which makes cholesterol (see the figure below).  In simple terms, it’s like re-directing a stream of water.

Role of statin in mevalonate pathway

Much of the understanding of the mechanism of action of statins has come from work in animal models, looking at the reduction in circulating cholesterol levels in the blood. We recently investigated the effect of two commonly prescribed statins on a marker of inflammation in white blood cells. In our experiments, we showed that this measured marker of inflammation was decreased in response to both statins, when the cells were first treated with a substance known to mimic the effects of viral infection. By using white blood cells in our experiments, we hypothesized a possible action of statins in blood vessels, to reduce inflammation inside the arteries of people with cardiovascular disease. This is in contrast to the traditional, clinical use of statins to lower lipids in the blood, the amount of circulating ‘fat’ which can be deposited in arteries and cause heart attacks and stroke.

What’s the connection between inflammation and disease?

It has been known for two decades that the underlying pathology in cardiovascular disease is rampant inflammation in the arteries. This inflammation is often due to fatty deposits, which cause red blood cells to clot in the arteries, and turbulence in the blood flow in this area. A number of other cells migrate to the region and release different chemicals, which contribute to the inflammatory reaction, much like you might see if you cut your hand and the wound becomes infected. Other causes of inflammation can be due to viral infections, like influenza. The point about inflammation in the arteries is that it happens over a long time and the markers of it are multiple, therefore, testing for it is still difficult. That is why your doctor will still take a medical history of your health overall, and of your family history.

I mention this because it is likewise known that markers of inflammation, like C-reactive protein for example, in people diagnosed with many kinds of cancer are increased, but only slightly. And two clinical trials looking at the use of statins, the PROVE-IT Study and REVERSAL Trial (reviewed by Salam, 2004) showed a reduction in C-reactive protein in the blood of people taking statins. For scientists, inflammation therefore presents a wonderful environment for experimentation.

Atorvastatin, picture credit

What about statins and cancer?

The author of the report Dr Carol Prives and her team work with p53 a well known tumour suppressor gene found in many but not all cancers, and the research referred to last week is at it’s preliminary stages. Dr Prives reports that the mevalonate pathway is significantly upregulated in tumours containing the p53 mutation. They do not say that statins have an effect on these tumours, merely that the same pathway of action of statins is implicated in p53-containing tumours (Freed-Pastor et al, 2012). This is interesting because it represents another line of research to look at the effect of statins in these tumours. But it should be remembered that cancer cells outside of the human body, such as those used in laboratory experiments, are often derived from people who had cancer and died a long time ago. Their cells have been immortalized and are continually cultured for use in experiments. The disadvantage of this is that sometimes it does not represent the true tumour response. The advantage, however, is that the cells are always the same and experimental data can be compared over time and between laboratories, unlike if we use different people (or animals) each time.

So, there is a long way to go before we can say that millions of lives will be saved by taking statins. And I’m pleased to say that a recent study has found that the number of deaths from heart attacks has halved in the last decade. Although, not all attributed to the use of statins, the results also reflect the drop in smoking, and increased awareness of heart health through good diet and exercise. But, according to one cardiologist, the real importance of statins is longer life, whichever way you look at it.

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