The Aerosol Tales
When I left Liverpool University in 1968, I was very familiar with the use of products distributed in aerosol cans.
- I had used aerosol shaving cream, although about that time, I acquired my beard.
- I certainly used aerosol deodorant, as did most in the 1960s.
- Aerosol paints were common for covering scuffs and scratches in your car.
- Aerosols were often used to apply sun protection.
- Aerosols containing cream or a non-dairy alternative for culinary use were not unknown.
- Aweosol lubricants were starting to appear.
Although, I went to work for the chemical giant; ICI, at that time, I had no idea how an aerosol and its can worked.
As ICI at the time, ICI were major manufacturers of aerosol propellants, I quickly learned how they worked.
The Wikipedia entry for Aerosol Spray Dispenser gives a lot of history about aerosol cans and their propellants.
The Wikipedia entry for Propellant has this paragraph describing propellants of the last century.
Chlorofluorocarbons (CFCs) were once often used as propellants, but since the Montreal Protocol came into force in 1989, they have been replaced in nearly every country due to the negative effects CFCs have on Earth’s ozone layer. The most common replacements of CFCs are mixtures of volatile hydrocarbons, typically propane, n-butane and isobutane. Dimethyl ether (DME) and methyl ethyl ether are also used. All these have the disadvantage of being flammable. Nitrous oxide and carbon dioxide are also used as propellants to deliver foodstuffs (for example, whipped cream and cooking spray). Medicinal aerosols such as asthma inhalers use hydrofluoroalkanes (HFA): either HFA 134a (1,1,1,2,-tetrafluoroethane) or HFA 227 (1,1,1,2,3,3,3-heptafluoropropane) or combinations of the two. More recently, liquid hydrofluoroolefin (HFO) propellants have become more widely adopted in aerosol systems due to their relatively low vapor pressure, low global warming potential (GWP), and nonflammability.
Note that the whole range of these chemicals, effect the ozone layer.
Rocksavage Works
ICI’s Rocksavage Works, was an integrated chemical plant by the Mersey,.
- It made all types of CFCs for aerosols and other purposes.
- It also made the fire suppressant and extinguisher; Bromochlorodifluoromethane or BCF.
- Alongside BCF, it made the anaesthetic Halothane or as ICI called it Fluothane.
- The plant was a poisonous place with all those bromine, chlorine and fluorine compounds.
- Despite this, the plant had a remarkable safety record.
I had the pleasure of working at the plant and it was where, I had most of my excellent Health and Safety training, from the amazing site foreman; Charlie Akers.
Some of the wisdom he distributed has proved invaluable in aiding my stroke recovery.
I suspect that since the signing of the Montreal Protocol, the plant has changed greatly or has even been closed.
All that appears to be left is the 800 MW gas-fired Rocksavage power station and a Facebook page.
Aerosol Baked Beans
In those days, I worked most of the time in a lab at Runcorn Heath.
One of the labs near to where I generally worked, in the large research complex, was a lab, where new aerosol products were developed and tested.
One of the standard jokes about that lab, was that they were working on aerosol baked beans. They said, they would develop the product, even of they had to eject them from the can one at a time.
Gift Time
One afternoon, the boss of the aerosol development lab came through with a tray of goodies.
On the tray, which was much like a cinema usherette’s ice cream tray of the sixties was a whole host of partly-labeled aerosol cans. Only clues to what the product might be were written on the outside in felt-tip pen.
I grabbed two, one of which was marked something like lubricating oil and the other was just marked hand cream, which I of course gave to my new wife; C.
We were married for nearly forty years and often, when she bought hand cream, she would remark, that it wasn’t of the same standard as the little can I brought home from work.
It appears to me, that one of the world’s top cosmetic companies and ICI were trying to create the world’s best and probably most expensive hand creams.
DMW
Fast-forward nearly twenty years and I was approached by Lloyds Bank about two individuals, who had developed an aerosol valve, that instead of using CFCs or other ozone-depleting chemicals.
- By the exploitation of the nether end of fluid dynamics, the propellant of the aerosol was nothing more harmless than pure nitrogen.
- I formed a company called DMW with the two inventors.
- John Gummer, who at the time was my MP and Environment Minister, knew of the aerosol valve and he took the details to Montreal.
So did a device developed in Suffolk help push through the Montreal Protocol?
Osbourne Reynolds
I also wonder, if we had some supernatural help. At the time, I lived in the family home of Osbourne Reynolds.
- He did a lot of the early work on fluid dynamics.
- He was the first UK Professor of Engineering.
- He was professor of Engineering at Manchester University for nearly forty years.
- The Reynolds number is named after him.
- Remarkably, students are sill taught on the equipment Reynolds designed.
- Reynolds was certainly one of our great Victorian scientists.
This Wikipedia entry gives more details of his remarkable life and work.
After Montreal the aerosol valve was sold to Johnson & Johnson.
DMW continued to develop other products and we had one, who no-one had any idea about how it worked.
So I discussed it with the Reynolds’s expert at Manchester University and he said he had no idea either.
But he was absolutely certain, that Reynolds would have known.
Application Of Control Engineering Principles To The Calculation Of Pharmaceutical Drug Doses
Today, I was asked by an eminent cardiologist to give my opinion on this scientific paper in the Journal of the American Heart Association, which was entitled Personalized Antihypertensive Treatment Optimization With Smartphone‐Enabled Remote Precision Dosing of Amlodipine During the COVID‐19 Pandemic (PERSONAL‐CovidBP Trial).
This was the background to the study.
The objective of the PERSONAL‐CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID‐19 Pandemic) trial was to assess the efficacy and safety of smartphone‐enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID‐19 pandemic.
These were the methods and the results.
This was an open‐label, remote, dose titration trial using daily home self‐monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5–7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10–12)/7 (95% CI, 6–7) mm Hg, P<0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events.
These were the conclusions.
Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App‐assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long‐term care.
About Myself
I am a Graduate Control Engineer, who graduated from the University of Liverpool in 1968.
I then worked at ICI in Runcorn for eighteen months, before moving to ICI Plastics Division, because of the untimely death of my father-in-law.
One of my tasks at Welwyn, was to look at control algorithms for chemical plants. For this I often used a PACE 231-R analogue computer.
Note.
- These computers could solve up to a hundred simultaneous differential equations at one time.
- They were programmed by wiring the various amplifiers and potentiometers together to simulate the equations.
- There were only a few transistors in these powerful machines, as all electronics were thermionic valves.
- Two of these machines wired together, were used to calculate the trajectories of the Apollo missions.
They were the unsung heroes of bringing Jim Lovell and Apollo 13 home safely.
Determining Control Algorithms
In a typical problem, I would model the a section of a chemical plant and the control system around it.
This would then lead to recommendations, as to the design and operation of the plant, so that it performed as required.
It could be argued that the body of an animal, is a very complicated integrated chemical plant, with a sophisticated control system.
For instance, if sensors around the body, say you are slightly low on fluids, your brain determines you should have a drink.
Many control loops on a chemical plant are controlled by proportional–integral–derivative controllers, which are commonly known as three-term controllers.
This is the first two paragraphs of the Wikipedia entry for three-term controllers.
A proportional–integral–derivative controller (PID controller or three-term controller) is a control loop mechanism employing feedback that is widely used in industrial control systems and a variety of other applications requiring continuously modulated control. A PID controller continuously calculates an error value
PID systems automatically apply accurate and responsive correction to a control function. An everyday example is the cruise control on a car, where ascending a hill would lower speed if constant engine power were applied. The controller’s PID algorithm restores the measured speed to the desired speed with minimal delay and overshoot by increasing the power output of the engine in a controlled manner.
I wouldn’t be surprised that the app in the smartphone used in the PERSONAL‐CovidBP Trial contained a form of three-term controller.
These are some points about three-term control algorithms.
Changing Of External Factors
One that was the villain in a problem, I dealt with, also affects my body – the weather.
I was asked to look at the problem of a chemical reaction, that overheated in hot weather. But the plant operators solved it by better insulation and ventilation of the plant and the standard three-term controller adjusted itself automatically to the new conditions.
After my stroke, I am on Warfarin for life. I test my own INR with a Roche meter and I have noticed that atmospheric pressure affects my INR. I change my deose accordingly, using a simple algorithm, of my own design.
The More You Test The More Precise The Control
If you take the cruise control example used by Wikipedia, speed is monitored continuously, as I hope, it would be if you were driving yourself.
But obviously, in many systems, where you are using an input with discrete values to control a system, you can’t be as precise as the data you collect.
When my son was dying from pancreatic cancer, he was fitted with a morphine pump, that he could adjust himself to dull the immense pain he was enduring.
- His nerves and his brain ascertained the pain level.
- He then adjusted the morphine level.
- He could get very precise control of his pain, because he was measuring it continuously.
But he was only using simple one-term control (proportional).
Derivative Control Can Be Difficult To Get Right And Can Even Go Unstable
Derivative control is mainly to stop overshoot, but sometimes you will find that it can go unstable, so two-term(proportional+integral) controllers will be used.
How I Control My INR
As I said earlier, I am on Warfarin for life and test my INR with a Roche meter.
The NHS typically tests patients about once every six weeks, which in my opinion as a Control Engineer is too infrequent.
I usually test myself a couple of times a week.
But every so often, I evaluate what daily dose gives me an equilibrium INR level of 2.5.
For the last three years, I have found a dose of 3.75 mg keeps me more or less on 2.5.
- As Warfarin comes in 1, 3, 5 and 10 mg. tablets, I alternate 3.5 and 4 mg.
- Warfarin tablets are easily cut in half using a sharp knife.
- I record INR and dose in a spreadsheet.
I have been doing this now for over ten years.
Is This A Unique Property Of Warfarin?
In this time, I have had five medical procedures, where surgeons were worried, that as I was on Warfarin, I might bleed too much.
For the first, which was to remove a lump from my mouth, the private surgeon wanted to charge extra for an anaesthetist. In the end, I asked what INR he wanted and he said 2.1 should be OK!
- So I reduced the Warfarin level and tested every day.
- I judged it correctly and had an INR of 2.1 on the day of the operation.
- The operation went incredibly well and I went home on public transport.
- The lump turned out to be benign.
- I’ve not had another lump.
After the operation, I increased the Warfarin level and tested every day, until it regained a level of 2.5.
On analysing my doses through the date of the operation, I found that the total amount of Warfarin, I didn’t take to reduce my INR to 2.1, was the same as I took to bring it back up again to 2.5.
Is this a unique property of Warfarin?
Since then I’ve had two cataract operations performed in a private hospital, where the NHS paid. Interestingly, they wouldn’t trust my own INR readings, so I had to get my GP to take the measurement.
I’ve also had gallstones removed by endoscopy at the local Homerton NHS hospital.
- For cases like mine, the hospital hire in a surgeon from the posh Wellington private hospital for one day a week, who brings the specialist tools needed.
- I wrote about this in Goodbye To My Gallstones.
- As it was a more serious procedure, I reduced my INR to a requested 1.0.
Interestingly, I still have my gall bladder, but the surgeon put it on notice to behave.
Conclusion
I would totally agree with the conclusion given in the PERSONAL‐CovidBP Trial.
Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App‐assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long‐term care.
I would add some conclusions of my own.
- The app used in the PERSONAL‐CovidBP Trial, seems to have had a good algorithm.
- I suspect the app could also be Internet-based.
These are some general conclusions.
- If you are on Warfarin and have access to a Roche meter, it is possible to lower your INR to the value required by a surgeon for an operation or a procedure.
- Since starting to take Warfarin, I have had four operations or procedures, where others would have had anaesthetic or a sedative.
- In those four operations, I was able to go home on public transport. If I still drove a car, I could have driven home afterwards.
- Private hospitals like to use an anesthetist, as it pumps up the bill.
- Avoiding anaesthesia must save hospitals money.
Well designed apps, based on Control Engineering principles, that help the patient take the best dose of a drug will become more common.
Coeliac Journey Through Covid-19 – Coeliac Diagnosis
Coeliac Diagnosis
My health was very variable as a child.
I would often have months off school and my health only really improved, when my parents bought a second home in Felixstowe, where we spent most of our holidays.
Perhaps it was the sea air, as going to Liverpool University didn’t seem to adversely affect my health.
I had been having gut problems for years and then in Autumn 1997, I didn’t see my GP, but a very elderly locum, who as I had recently had my fiftieth birthday, gave me a present of my first blood test.
It turned out that I was very low on B12 and a course of B12 injections was arranged.
As the injections didn’t raise my levels, an appointment was made to see a consultant at Addenbrooke’s Hospital in Cambridge.
It was a Monday, when I went to the appointment and after a quick chat and no examination, the consultant said that they would take some blood. Which they did!
Within forty-eight hours a letter arrived on my door-mat saying that I was probably coeliac and it would be confirmed by endoscopy.
Two endoscopies without sedative or anaesthetic were performed and I was confirmed as coeliac.
The first was performed by Dr. Richard Hardwick and the second by Dr. Rebecca Fitzgerald.
My gut health has been better since, I’ve been on a gluten-free diet, backed up by three-monthly B12 injections.
A few years later, I was talking to a gastroenterologist in Cambridge and he told me that he thought he had more coeliac patients than any other in England.
The manager of Carluccio’s in the city, also told me that they sold a very high percentage of gluten-free food.
Were Cambridge testing a genetic test for coeliac disease or was it just a Whack-A-Coeliac policy?
They certainly had everything geared up for high-speed diagnosis. They even did the endoscopies without a sedative, so they didn’t need any recovery beds.
The Anonymous Widower 