Archive for the ‘medication’ Category
A bit about schizophrenia – a very bizarre ailment
Having, for a book group, read a strange novel written a little over 50 years ago, by Doris Lessing, Briefing for a descent into hell, the title of which may or may not be ironic, and being reasonably interested in the brain, its functions and dysfunctions, I’ve decided to use this post to update my tiny knowledge of schizophrenia, a disorder I’ve had some acquaintance with.
Lessing’s book may or may not be about schizophrenia, because it doesn’t concern itself with labeling any mental disorders, or with the science of brain dysfunction in any way. The focus is upon the imaginative world of an Oxbridge academic, a lecturer in classical mythology or some such, who, having been found wandering about in some Egdon Heath-type landscape, with no identification papers or money, and a lack of proper lucidity, is brought into a psychiatric facility for observation and treatment. The vast bulk of the book is told from this individuals’s perspective. Not that he tells the story of his illness, he simply tells stories – or Lessing tells stories on his behalf. Somehow the reader is allowed to to enter the main character’s inner landscape, which includes a voyage around the Pacific Ocean, another voyage around the solar system (conducted by classical deities) and harrowing, but fake, war-time experiences in the Balkans. Along the way we’re provided with the occasional dazzling piece of insight which I think we’re asked to consider as the upside, or mind-expanding nature, of ‘madness’ – somewhat in the spirit of Huxley’s Doors of Perception and Timothy Leary’s psychedelia. At the end of the book the professor is returned to ‘normality’ via electric shock treatment, and becomes, apparently, as uninteresting a character as most of the others in the book, especially the doctors responsible for his treatment, only known as X and Y.
So, there are problems here. First, Lessing’s apparent lack of interest in the science of the brain means that we’re at a loss to know what the academic is suffering from. Madness and insanity are not of course, legitimate terms for mental conditions, and Lessing avoids using them, but offers nothing more specific, so we’re reduced to trying to deduce the condition from what we know of the behaviour and ramblings of an entirely fictional character. I’ve come up with only two not very convincing possibilities – schizophrenia and brain tumour. A brain tumour is a useful literary device due to the multifaceted nature of our white and grey matter, which constitutes the most complex organ in the known universe, as many an expert has pointed out. A benign tumour – one that that doesn’t metastasise – may bring on a multiplicity of neurons or connections between them that increase the ability to confabulate – though I’ve never heard of such an outcome and it’s more likely that our ‘imagination’ is the product of multiple regions spread throughout the cortex. Schizophrenia only really occurs to me here because the professor was found wandering ‘lonely as a cloud’, far from home, having had his wallet presumably stolen, so that it took some time to identify him. This reminds me of a friend who has from this condition, and has suffered a similar experience more than once.
One of the symptoms of schizophrenia is called ‘loss of affect’, which means that the sufferer become relatively indifferent to the basics – food, clothing and shelter – so caught up is he in his mental ramblings, which he often voices aloud. It’s rare however, for schizophrenia to make its first appearance in middle-age, as appears to be the case here. Another reason, though, that my thoughts turned to schizophrenia was something I read online, in reference to Briefing for a descent into hell. I haven’t read any reviews of the book, and in fact I had no idea when the book was published, as I’d obtained a cheapie online version, which was undated. So in trying to ascertain the date – 1971, earlier than I’d expected, but in many ways illuminating – I happened to note a brief reference to a review written when the book came out, by the US essayist Joan Didion. She wrote that the book presented an ‘unconvincing description of mental illness’ and that the book displayed the influence of R D Laing. A double bullseye in my opinion.
I read a bit of R D Laing, the noted ‘anti-psychiatrist’ in the seventies, after which he went decidedly out of fashion. His focus was primarily on schizophrenia – as for example in his 1964 paper ‘Is schizophrenia a disease?’ – though he treated other psychoses in much the same way as ‘a perfectly rational response to an insane world’. This is doubtless an oversimplification of his views, but in any case he seems to have given scant regard to what is actually going on in the brain of schizophrenics.
Since the sixties and seventies, though, and especially since the nineties and the advent of PET scanning, MEG, fMRI and other technologies, the field of neurology has advanced exponentially, and the mental ailments we suffer from are being pinpointed a little more accurately vis-à-vis brain regions and processes. I’ve noted, though, that there’s still a certain romantic halo around the concept of ‘madness’, which after all human society has been ambivalent about since the beginning. The wise fool, the mad scientist and the like have long had their appeal, and it may even be that in extremis, insanity may be a ‘reasonable’ option. As for schizophrenia, maybe we can live with our ‘demons’, as was apparently the case for John Nash after years of struggle, but it’s surely worth trying to get to the bottom of this often crippling disorder, so that it can be managed or cured without resort to disabling or otherwise unhealthy or inconvenient dependence on medication.
Schizophrenia is certainly weird, and its causes are essentially unknown. There’s a genetic element – you’re more likely to suffer from it if it runs in the family – but it can also be brought on by stress and/or regular drug use, depending no doubt on the drug. It’s currently described as affecting a whopping one in a hundred people (with enormous regional variation, apparently), but perhaps if we’re able to learn more about the variety of symptoms we might be able to break it down into a group of affiliated disorders. There is no known cure as yet.
One feature of the ‘neurological revolution’ of the last few decades has been the focus on neurotransmission and electrochemical pathways in the brain, and dopamine, a neurotransmitter, was an early target for understanding and treating the disorder (and may others). And that’s still ongoing:
Current research suggests that schizophrenia is a neurodevelopmental disorder with an important dopamine component.
That’s from a very recent popular website, but research is of course growing, and pointing at other markers. A reading of the extensive Wikipedia article on schizophrenia has a near-paralysing effect on any attempt to define or describe it in a blog post like this. Glutamate, the brain’s ‘most abundant excitatory neurotransmitter’, has been a major recent focus, but it’s unlikely that we’ll get to the bottom of schizophrenia by examining brains in isolation from the lived experience of their owners. Genetics, epigenetics, stress, living conditions and associated disorders, inter alia, all appear to play a part. And due to its strangeness, its apparent hallucinatory nature, its modern associations of alienation and dystopia – think King Crimson’s ’21st century schizoid man’ and much of the oeuvre of Bowie (mostly his best work) – it’s hardly surprising that we feel something of an urge to venerate the schizoid personality, or at least to legitimate it.
Meanwhile, research will inevitably continue, as will the breaking down of intelligence and consciousness into neurotransmission pathways, hormone production, feedback loops, astrocytes etc etc, and ways of enhancing, re-routing, dampening and off-on switching neural signals via increasingly sophisticated and targeted medications… because a certain level of normality is optimal after all.
Meanwhile, I’m off to listen to some of that crazy music….
References
https://www.verywellmind.com/the-relationship-between-schizophrenia-and-dopamine-5219904
https://www.verywellmind.com/what-is-dopamine-5185621
Covid 19: corticosteroids, inflammatory markers, comorbidities
Canto’s bronchiectasis – a relatively mild case, thank dog
Canto: So update 87, in late June, reflects a period when daily cases were just starting to rise, but deaths were apparently reducing – and various reasons were being given for this.
Jacinta: And interesting to note all the skepticism around Oxford University’s dexamethasone trial, which has led (the trial, not the skepticism) to a huge demand for the steroid. Dr Paul Sax of Harvard Medical School has expressed some dismay at the negativity, as this was a randomised controlled trial (RTC) of a widely available drug by a highly reputable, government-funded institution.
Canto: Yet it seems that the website on this trial has since been taken down, so maybe there are some issues…
Jacinta: Okay, so let’s move on. Dr Seheult talks about raised ‘inflammatory markers’ in patients he observes coming in with covid-19. He names them, and I want to do a shallow dive into what they are and what they mean: Ferritin, C-reactive protein (CRP), CPK (to do with muscle breakdown), erithrocyte sedimentation rate (ESR), and d-dimer levels. So, ferritin is an iron-containing protein. It stores the iron and releases it when needed. Ferritin is mostly concentrated in the liver cells (hepatocytes) and in the reticuloendothelial cells of the immune system. That endothelial word again. As for CRP, this abstract from a 2018 paper Frontiers in Immunology tells me that ‘C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation….CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes’. Need I say/quote more? And on CPK, this from the Johns Hopkins Lupus Center:
Creatine phosphokinase (a.k.a., creatine kinase, CPK, or CK) is an enzyme (a protein that helps to elicit chemical changes in your body) found in your heart, brain, and skeletal muscles. When muscle tissue is damaged, CPK leaks into your blood. Therefore, high levels of CPK usually indicate some sort of stress or injury to your heart or other muscles.
And the US website medicineplus.gov has this to say on ESR:
An erythrocyte sedimentation rate (ESR) is a type of blood test that measures how quickly erythrocytes (red blood cells) settle at the bottom of a test tube that contains a blood sample. Normally, red blood cells settle relatively slowly. A faster-than-normal rate may indicate inflammation in the body.
So, a fast ESR is an inflammation marker. High levels of CPK in the blood are too, presumably, as are high levels of CRP, wherever. And ferritin. Lastly, d-dimer levels, which are also related to clotting. This Australian site, healthdirect, tells me that ‘D-dimer is a type of protein your body produces to break down the blood clot’. So, a d-dimer test is ‘a blood test usually used to help check for or monitor blood clotting problems. A positive test means the D-dimer level in your body is higher than normal and suggests you might have blood clots’.
Canto: With all that let’s continue with the update. In Seheult’s hospital they started using dexamethasone as soon as the Oxford results came out and they’ve seen a reduction in all these rising inflammation markers. He recognises issues here though. Is this just anecdotal? Is this just a drop in the markers without real-life effects? Could it be recall bias? We know how conveniently inaccurate memory can be.
Jacinta: My impression is that’s not going so well, though there’s no doubt still a varied use of dexamethasone and other corticosteroids throughout the USA. We’re at the point with the updates where they’re still thinking deaths in particular are reducing. We now know better. So the update next looks at a Chinese study from mid-June entitled ‘clinical and immunological assessment of asymptomatic SARS-CoV2 infections’. This small study looked at 37 asymptomatic patients and found that viral shedding (the release of virus from an infected person into the environment – the period of contagiousness) was 19 days, presumably on average. This compared with 14 days for symptomatics. A pretty significant finding. Immunoglobulin G (IgG) levels – essentially antibodies – were about six times higher in the symptomatic cases. That seems unsurprising I think, because it’s the antibodies that largely create the symptoms – the inflammation and clotting, the cytokine storm. Another finding was that, eight weeks after being discharged from hospital, the asymptomatic cases were 40% seronegative (having no antibodies) against SARS-CoV2, compared to 12.9% for the symptomatic cases. This suggests that neutralising antibodies may be ‘disappearing’ over time, though other immune cells, such as T cells may have a mitigating effect. Overall, though, the study advises extreme caution:
Together, these data might indicate the risks of using covid19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups and widespread testing.
Canto: Not suggestions the current Trump administration would be likely to pay attention to.
Jacinta: Well the question here is one of re-infection, and I don’t know if there are any clear answers to that. Anyway update 87 goes on to look again briefly at vitamin D, and research in the UK, where vitamin D deficiency is more of a problem, and is associated with viral chest infections and with covid19 outcomes, with people of colour being disproportionately affected. They’re looking to people to sign up with a study called ‘covidence UK’. Dr Seheult also looks at a ‘Research Letter’ from the JAMA network entitled ‘prone positioning in awake, non-intubated patients with covid19 hypoxemic respiratory failure’. Prone positioning – lying on your tummy – was highlighted in one of the earliest of these covid19 updates as improving the symptoms of patients with ARDS. The findings from this JAMA are instructive:
In this small, single-centre cohort study, we found that the use of the prone position for awake, spontaneously breathing patients with covid19 severe hypoxemic respiratory failure was associated with improved oxygenation. In addition, patients with an SPo2 [pulse oximetry, a measure of blood oxygen level] of 95% or greater after one hour of the prone position was associated with a greater rate of intubation.
So, though there’s a need for RCTs etc etc, Dr Seheult has found dramatic improvements in oxygenation in his own patients through prone positioning.
Canto: Who are we to argue? And this update 87 ends on a positive note due to these combined findings about treatment. Prone positioning, remdesivir, dexamethasone, vitamins D and C, zinc, and maybe convalescent plasma, which needs to be explored further..
Jacinta: That’s blood plasma from recovered covid19 patients, with of course the antibodies to go with it, and I’ve looked at the National Covid19 Convalescent Plasma Project website to see if there are recent studies on this, but there’s nothing since March – small studies from China, which seem promising.
Canto: Update 88 starts again with dexamethasone, the cheap and widely available steroid, which – and this is back in late June – the British government got behind after the Oxford study was published, authorising its use ‘for patients hospitalised with covid19 who required oxygen, including those on ventilators’. It’s interesting that clinical views have changed on corticosteroids for covid19 over time, and there are still concerns about dosage and time periods on the drugs.
Jacinta: Yes, short courses of corticosteroid treatment seem to be recommended, and not just dexamethasone. And many studies showed this before the release of the Oxford data.
Canto: So the Oxford data itself is fascinating, especially for comorbidities or previous conditions. Especially interesting to me as I have such a condition, one that fits under their heading ‘chronic lung disease’, in my case bronchiectasis. They’re finding that people with such conditions are ending up on ventilators far less than those with diabetes or heart disease. So that’s good news for me. The disease, as they’ve been finding, is that covid19 is essentially an inflammatory disease of the vascular system. However, it seems that Dr Seheult’s hopes, at the end of update 88, that the greater introduction of short-term corticosteroids, and the use of other medications that might be efficacious, would reduce the mortality rate, have been dashed. We’ll be interested to find out why in upcoming posts.
References
Coronavirus Pandemic Update 87: More on Dexamethasone; Do COVID-19 antibodies last?
Coronavirus Pandemic Update 88: Dexamethasone History & Mortality Benefit Data Released From UK
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908901/
My current health condition 2: searching for a diagnosis
It is easier to find men who will volunteer to die, than to find those who are willing to endure pain with patience.
Julius Caesar (and I’m willing to volunteer)
I haven’t been much in the mood for writing. You could say I’m feeing sorry for myself, or indulging in the pain I’m experiencing, but truth to tell, my current condition doesn’t make it so easy to ‘rise above myself and grasp the world’. I’m hoping at least to rise above my own pain and grasp the world of pain in general! But before I look at the ‘philosophy of pain’ I should update my situation.
The pain – shooting down from the left shoulder – first became acute on February 29. On that Saturday I arrived in an ambulance at Royal Adelaide Hospital, was examined, questioned and released without a diagnosis. Panadol, administered by the paramedic in the ambulance, had relieved the worst of the pain. I bought over the counter medication, ibuprofen and paracetamol, and using them at the upper limit of, and perhaps beyond, what was recommended, I was able to work at Eynesbury College on the following Monday and Tuesday. On Wednesday I visited my GP. I was referred to St Andrews Hospital for an ultrasound and an x-ray. The GP told me that if the pain subsisted or worsened the hospital could give me a corticosteroid injection in the shoulder, which he thought would do the trick, painwise.
Meanwhile I was doing my own research. It seemed that bicipital or biceps tendinitis was the best fit. There was also bursitis and some kind of rotator cuff damage. I couldn’t think of an obvious cause, the only ‘different’ activity I’d been engaging in was lawn bowling, generally associated with geriatrics and hardly recognised as strenuous activity. However, when Sarah, who was also doing some research, noted that one line of enquiry led to ‘dangers and injuries from lawn bowling’, I felt less dismissive.
My appointment at St Andrews was for Friday (March 6), but on Thursday a felt increase in pain had me asking Sarah to ring the GP for stronger medication. I was prescribed ibuprofen plus codeine, which I started taking, again pushing beyond the recommended limits. However, my subjective sense told me that paracetamol was more effective than ibuprofen. Yet ibuprofen was an anti-inflammatory, paracetamol was not. It was all very confusing. Did I have pain without inflammation? How could this be?
I was driven to St Andrews hospital next morning, where I was given, first an X-ray, then an ultrasound test. This was a first for me, and I was able to watch the screen as the young woman administering the test slowly moved the scanner across my shoulder region. From her silent response and my own observation of a kind of softly rolling ocean of muscle disappearing into the distance, I got the strong impression that there was nothing untoward, no sign of damage or dysfunction.
Meanwhile, the pain continued, together with difficulty sleeping, and a general lethargy, which might just be a sort of depression at the sense of restricted movement. I noted that I felt physically at my best when lying still, on the sofa or my bed. Just getting up resulted in shooting pains. Reading, holding a book, was a pain. All of this was on my left side, and I’m very left-handed.
And so it went, until something dramatic happened, I think it was on Sunday (March 8). I experienced severe constipation, certainly unlike anything I’d ever experienced before, and I won’t go into the shitty details, though it did make me think of my mortality (as has this experience of pain in general). How many people have died on the toilet seat? A dirty little secret, no doubt. In any case, I recovered, and, upon further desperate research (and noting that, before this bout, I hadn’t done a ‘number two’ for days – how had I missed that?), I dropped the ibuprofen plus codeine medication and went back to paracetamol.
I work part-time at Eynesbury College, currently two days a week (Monday and Tuesday), barely enough to live on, as a teacher of academic English to foreign students. It’s the most poorly paid job in the teaching profession. I’m paid as a casual, and work from five-week contract to five-week contract. It’s anything but ideal. For example during this current contract, which ends tomorrow (Friday), there were two public holiday Mondays, for which I wasn’t paid. I was offered another five-week contract starting next week, but I’ve made a decision to decline the offer, hoping to get on top of this pain situation once and for all.
I won’t go into my parlous financial situation, but it’s important due to my status vis a vis subsidised health care. More about that anon.
So I worked on Tuesday, and it was something of a struggle. Yesterday (Wednesday March 11) I returned to my GP and received the report from St Andrews Hospital. So I’ll now present the findings together with my comments.
X-ray and ultrasound left shoulder with subacromial bursal injection
subacromial bursitis has to do with inflammation of the bursa that separates the upper surface of the supraspinatus tendon (one of the rotator cuff set of tendons) from the overlying coraco-acromial ligament, the acromion, and the coracoid. To be explored further. A bursa, or synovial bursa, is a fluid-filled sac which cushions connections between bones, tendons, ligaments etc in joints.
X-ray – no bony injury. Alignment is normal. Subacromial space is preserved. No subacromial calcification.
Nothing to see here.
ultrasound- biceps tendon intact. No fluid in the sheath. The tendon does not sublux during internal/external rotation
Nothing again. Subluxation is a partial or incomplete dislocation of a joint or organ.
supraspinatus and other rotator cuff tendons are intact. No tear or tendinopathy. The subacromial bursa does not appear thickened and no bursal drag with abduction is identified.
So there are four rotator cuff tendons or muscles (not too sure of the difference); supraspinatus, infraspinatus, teres minor and subscapularis. The subacromial bursa is as described above.
The AC joint is normal in appearance and remained stable during forward flexion.
This is the acromioclavicular joint, at the top of the shoulder. It feels to me that the pain comes from ‘inside’ and lower than the shoulder, but it’s actually difficult to locate precisely. It may be a problem with the acromion, however. Or the Glenoid cavity or labrum. It may be a SLAP lesion (symptoms include ‘trouble localising a specific point of pain’. SLAP stands for ‘superior labrum, anterior to posterior’.
I’ll no doubt have to see a specialist, and the worry now is money