Expert Breakfast Report for 21 Sept 2022: Dr Jim Faed, Dept of Pathology

Yet another fascinating presentation by a highly experienced specialist, in which he talks about, and explains, a number of cases with which he has been involved, as well as touching on his various research projects.

Dr Faed’s family were originally from the UK and Australia but settled in the Waikato and later moved to Northcote, which is an Auckland suburb, but in those days was farmland, where his father was a market gardener. His mother was a home-maker, who was constantly subjected to Jim enquiring, “Why?” Demonstrating curiosity about everything from an early age, sometimes frustrating his mother as she didn’t know all the answers! One day in the market garden he came across the remains of a dead cat, at this stage no more than a dried skeleton. He collected all the bones and glued them together to resemble in the original shape of a cat.

Together with having a ‘greenstick’ leg fracture and appendix removal, he became acquainted with hospitals -– though for him partly as a place of boredom, since there was nothing to do but lie in bed and count the number of carriages on the trains he could see passing. But these events introduced him to health, and seeded his aspirations of going into medicine.

Attending a small rural primary school, “We had a teacher who just extended me quite a lot, that was probably one of the critical things.” When he reached university age, Jim had still not studied any biology, and got hold of someone’s year 1 zoology notes, from which he learnt about “all those things from amoebae to chordates and vertebrates.” In those days, in the early 1960’s, the only Medical School in New Zealand was Otago, and Auckland Uni was assigned 20 places to fill at it. To his amazement, he was successful in his application. In 1964, travelling by train, ferry, and more trains, he arrived in Dunedin and discovered this “two-storey city.”

Medical education was a little different in those days. There was no introductory material. In week 1 on the Saturday morning, the first dissection class was scheduled. There was absolute silence as 120 students in their short white coats (to distinguish students from seniors) embarked on an activity completely strange to them. The professor was Bill Adams, a man of great gravitas, but who enjoyed baiting the students sometimes. And so they set to work on cadavers. “We have come a huge distance since those days, and most of it is for the better.”

Haematology and Blood Transfusion

Inspired by pathologist Bruce Howie, one of his teachers who specialised in blood, Dr Faed decided to do the same. It was still relatively early days in blood transfusion practice in the late 1950’s when Bruce Howie took over the blood supply soon after there had been a series of deaths due to blood transfusion. It turned out that this was due to a defective autoclavinge run. At a time when blood was stored in glass bottles, a batch of bottles had been inadequately sterilised, resulting in a number of patients being transfused with infected blood. At this point Dr Faed asked if anyone present was a blood donor, he congratulated the two who responded, and encouraged them to recruit their red-blooded fellow students to be donors.

Adam's (College's Business & IT Manager) Donor Certificate

In those days there were a few hundred donations a year, whereas now it is about 6,000 - “and it’s a very different scene”.

Dr Faed was among the first group of medical specialists to qualify in New Zealand in contrast to going overseas to qualify. As a pathologist, Jim was attempting some cancer immunology research, but the tools he needed were not available here. Consequently he spent some time in Sydney in an immunology lab, then on to the Edinburgh Transfusion Centre, where he had a “great experience”. He noted that the street plan of Edinburgh was simply imposed on the Dunedin landscape without reference to the actual terrain, which is what led to Baldwin Street being the steepest in the world, as well as so many the street names being the same in Dunedin. There he worked on cell culture growth media using liposomes, finding that all the fat soluble vitamins are essential for cell growth.

The Dunedin Child Development Longitudinal Study

Returning to New Zealand after 23 years abroad, he took up the transfusion post in Dunedin Hospital, just six months after the hospital had been opened. He had a number of small research projects going, including playing a part in Phil Silva’s Longitudinal Child Development Study, one of the top studies of its kind in the world (https://dunedinstudy.otago.ac.nz/). This group, consisting of people from many different disciplines, studied all the children born over one year at the Maternity Hospital, with the children recalled every year for further examinations. Among other things they were able to correlate all kinds of social disconnects, such as violence, criminal behaviour, etc, with early childhood factors.

Dr Faed’s involvement was with a range of blood studies. One of these was the heavy metal lead – lead exposure is assessed by the amount in red blood cells. Painters who sanded down old buildings to repaint them exposed themselves to fine dust containing lead from the original paint. Those working with batteries are another vulnerable group, and anyone exposed to lead can become very ill. 

Basophilic stippling of red cells in lead poisoning — Image by: John Cross

Jim described a case of a young woman who was cleaning down an old house for repainting, two days before Christmas, who felt very, very tired, and he suspected lead poisoning, telling her to “get a test tomorrow “. When the test results became available, she was rushed off to Christchurch hospital for treatment on the day before Christmas. “Keep your eyes open for the odd things that come past you, and try and ‘stitch it together’, and then you’ll start to make developments.”

Meningococcal Meningitis and Protein C

Moving on to 2002, Dr Faed then talked about the extensive meningococcal meningitis epidemic that hit New Zealand. Neisseria meningitides is a gram-negative organism which causes meningitis, but is most dangerous when a blood infection (septicaemia) develops. It is mainly young children and young adults that suffer from it, older folk having developed immunity to the organism. “We had some young folk come in with overwhelming sepsis. They were going into septic shock, developing a dreadful bleeding problem, lung injury, and dying - and about half of them did die.” Although a high dose of the antibiotic ceftriaxone will kill the organisms, their bacterial metabolic products - notably endotoxin - remains in the patient’s circulation. Endotoxin triggers a massive shock reaction, affecting the lining of blood vessels to the extent of producing DIC (disseminated intravascular blood coagulation). A major player is Protein C, which is involved in preventing blood coagulation. As the level of protein C falls, DIC gathers pace. Following up pilot studies in Ireland, they tried exchanging the patients’ plasma for fresh normal plasma, a process called plasmapheresis. In this way the level of protein C, as well as other clotting inhibitors, was raised in the patients, and most of those treated in this way survived. The ones who did not were already too severely affected before the treatment was begun. In theory they could be put on a heart-lung machine so the lungs are rested while they recover, but no-one has tried that, as it would lead to other very serious difficulties. Uppermost in those is that the lungs would become so fibrosed that a quick lung transplant would be needed. However, that is not possible, lungs being “the hardest organ in the whole body to transplant.”

The Bleeding Patient

One of his other ‘small research projects’ involved the improvement of a blood product called cryoprecipitate, which at that time came in 40 ml lots, requiring the anaesthetist to administer perhaps 12 of them to a patient who was losing blood, while at a time when they also needed to be working on other tasks. By improving the precipitation process to improve the yield of the blood protein fibrinogen, the precursor of the fibrin strands that forms the framework of a clot, they were able to reduce the number of cryoprecipitate bags needed down, sometimes as low as 2 bags. Another issue is that blood coagulation (which is quite a complex process) was poorly understood by anaesthetists at that time, and they would rely on blood tests which took at least an hour to perform, by which time the results were most probably irrelevant. That was much improved by Dr Faed, with his in-depth knowledge of coagulation, being in the operating theatre and able to assess the haemorrhagic state of the patient very rapidly and “design a replacement programme for the individual patient.” The result was a considerable reduction in such incidents. “So I had a very close working relationship with the surgeon and anaesthetist in that team” such that, as Dr Faed approached the end of his career, one anaesthetist said, “What’s going to happen when Jim retires?” But he hasn’t yet! Jim did recommend buying a machine called a thromboelastograph which, by giving a dynamic assessment of clot formation is much quicker than the old lab tests for indicating the appropriate therapy.

The problems with bleeding are most commonly seen in cardiac surgery due to such factors as:

1. Blood is being pumped by a machine outside the body, so extra blood volume is needed, maybe doubling the fluid volume. The clotting factors are therefore halved in concentration.

2. Because the body is cooled down generally for a substantial period, the liver is not synthesising replacement coagulation factors as quickly as normal.

Dr Faed described a case in Wellington involving replacement of all four heart valves with the surgical team involved for a total of 16 consecutive hours on a day when he was on national call. The anaesthetist called him at 2 am next morning as the patient’s bleeding was not under control. He felt the biggest problem was that they had been “on the go for 16 hours”, “You can’t work well in those circumstances, not even on those crazy swot sessions students have before an exam. Am I right?” For the surgery patient, he prescribed a mix of four clotting support products, which sorted out the bleeding problem, “and everyone was happy!” Jim also pointed out to the Wellington anaesthetist that this patient would be further down the track to recovery than usual under the circumstances, and they must not delay with the usual post-op. anticoagulant therapy. The surgical team were initially puzzled by this, as it had not occurred to them, no doubt due to their exhausted state! Any event involving substantial inflammation, such as surgery or a major car-accident increases the risk of thrombosis and it is routine to give an anti-clotting medicine - an anticoagulant, for a short period after surgery.

“You can solve problems if you’ve got the integrated knowledge, and you can help people on the fly - and it works.”

The Immunoglobulin Story

Another case involved an elderly woman affected by an auto-immune disease which was attacking her nerves and stopping nerve impulse conduction. Already very weak, she would soon reach the stage of being unable to breathe. The neurologist asked if it was possible to carry out plasma exchange to reduce the auto-antibody level. This would be risky in a frail old lady, and Dr Faed instead suggested they try giving her a high dose of immunoglobulin as this works in a different auto-immune condition where the platelets are very low (ITP - idiopathic thrombocytopaenic purpura). “So we did. And ‘hey presto!’ she started to improve.” Five days later she was out of bed and starting to walk. “That was a huge discovery for a neurologist” - because most often treatment for serious neurological disorders was no more than palliative care. A group in Holland had done a similar study at the same time, and published their results first. “So they get most of the credit . . but the Dunedin paper has been cited about 80 times.” Now high dose immunoglobulin - which is made from the blood of healthy donors - is used much more commonly for a wide variety of conditions.

Another similar case was a lady from Nelson, who was treated here (in Dunedin) then returned to Nelson. She wrote to the neurologist saying: ”Today I walked, danced, sang and skipped along the beach at Nelson, and it was all because of the treatment I received.” Jim said, “When you have done something like that to a patient’s life, you know you have done at least one good thing.”

Stem Cells

Another area of research is stem cells, currently badly affected by lack of funding. Dr Faed feels that much more work is needed on the use of autologous stem cells (stem cells harvested from the patient themselves), rather than cells from another person, as autologous (your own) cells remove the need for immunosuppressive drugs with their sometimes severe side effects.

The Massive Importance of Iron - and Keep Saying “Why?”

Dr Faed first pointed out that every living creature, from animals to plants and microbes, needs iron to survive. Iron is not only a key component of haemoglobin for carrying oxygen, but is a key element in many enzymes, which “without that an iron cluster is a piece of non-functioning protein junk.” The generation of the source of energy in cells, ATP, in mitochondria is dependent on iron, and tiredness can be a result of iron deficiency. Causes of iron deficiency include menstruation, blood donation by females in particular, and also pregnancy. “Unless you are a red meat eater you may not succeed as a blood donor - vegetarians and vegans often fail as blood donors.” Iron is very difficult to absorb from food. Only around 2% of iron in vegetables is absorbed, and around 10% in red meat is absorbed.

Iron is particularly important in the development of the fetus. Cognitive disorders such as Attention Deficit/Hyperactivity Disorder (ADHD), autism and intellectual disability can result from iron deficiency in the foetus. While these are often mainly genetically determined disorders, the risk for them conditions is much higher if a fetus is iron deficient. There are some parts of the brain where the iron level is ‘set’ in foetal life and it becomes impossible to increase that level later. “That’s not known by many in the medical profession, so I’m telling you something that’s quite hot knowledge.” “I believe one of the things we must focus on as a key public health issue is the iron status of women of childbearing age, because women who might become pregnant must have an adequate iron status to provide for that fetus.”

Asked how he maintains his passion over such a long career (he gained his specialist qualification in 1976), Jim said, “It’s seeing things and making a difference. There are always interesting things. As a young child I kept asking that question ‘Why?’, and I keep on asking ‘Why’”

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Posted: Wednesday October 5, 2022