Cystitis unmasked
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Cystitis unmasked

Malone-Lee MD FRCP, James

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Cystitis unmasked

Malone-Lee MD FRCP, James

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Modern science has shown that the widely held beliefs of clinicians about urinary tract infection (UTI) are wrong. A large body of meticulous, rigorous data, from different centres around the world makes this point. How can it be that doctors continue to practise in contradiction of what we now know? A few clinicians are now changing their approach with gratifying results so it is timely to encourage others to do likewise. Clinical guidelines have achieved such influence that most doctors feel compelled to follow them and may face censure if they do not. Regrettably the guidelines are mistaken and contradict the known science. The inertia of bureaucracy and the fear of antimicrobial resistance (AMR) do not help to encourage reflection. However, things are changing and the future should see new and better informed advice. It is a tragedy that these circumstances are leading to widespread suffering amongst many women, some men and children who experience untreated or inadequately treated infection that may plague them for years. This situation has to change. This book sets out the truth about this neglected field and explains the many errors that haunt the topic. The style makes the message accessible to all clinicians. The story is convincing, because the clinical stories that illustrate the text will be so familiar to practising clinicians, who have been baffled by their experiences. Above all, this book will help you and your patients by detailing an accessible, practical approach to resolving this difficult clinical problem in common practice. The scope of the book will cover: the history of the medicine of urinary tract infection (UTI); the urinary microbiome and what the microbes are really up to; the battles between the pathogens and the innate immune system; the truth about the tests and the criteria used to define UTI; antimicrobial resistance and the importance of Darwinian evolution; the science and ground-breaking research on UTIs; the use of antibiotics; successful treatment; supportive and other related treatments; ethics; the future; and, above all, the experiences of the patients. James Malone-Lee is an Emeritus Professor of Medicine at University College London (UCL). For 37 years as a clinical scientist at UCL he studied lower urinary tract symptoms. His research group made discoveries that challenged numerous strongly held beliefs about lower urinary tract disease, particularly infection. For many years this new knowledge was rejected by many, but in the wake of corroborative evidence from others around the world, this new thinking is becoming more widely accepted.

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Chapter1
The intriguing history of urinary tract infection
The history of medicine is full of cautionary tales relevant to modern practice, but we keep reoffending, returning enthusiastically to the mistakes of the past. Why should this be? Perhaps this story of cystitis may shed some light on this bizarre mystery.
Cystitis is one of our most common bacterial diseases. It is much assumed to be a simple, uncomplicated condition which resolves easily. In 70% of cases that is true, but when unchecked it proves itself an appalling affliction, devastating lives and wreaking untold misery. Regrettably, the 30% who prove unresponsive are frequently the victims of intolerance. Science tells us how to respond to the 30% but modern guidelines, which just address the 70%, insist on rejecting what science suggests. There is worse to come since the ill-considered use of ‘big data’ threatens to average exceptional patients out of consideration.
Sumerian clay tablets from Mesopotamia (3000 BCE), Babylonian tablets (1700 BCE), and Egyptian hieratic writing in the Ebers Papyrus of circa 1500 BCE describe uroscopy, the contemplative examination of the urine. These civilisations recognised three groups of healers: physicians, priests and sorcerers. For urinary tract infection (UTI), the Egyptians prescribed rest and herbs, prayers, incantations and spells, and hence the necessity for a multidisciplinary team. As this book develops we shall see that we do not appear to have advanced much on that.
Prayer remained an important intervention for many centuries. The Greeks invoked Asklepios in seeking health, but it is unknown whether there was a god for UTI. However, come Christianity and the Middle Ages, the hermit St. Vitalis of Assisi (1295 to 1370) became the patron saint of bladder and genital afflictions. Should you consider a pilgrimage, his relics are preserved at San Vitale, a small village near Assisi in Italy, where today our patients gather to pray for deliverance from the torment that has defied our protocols; there’s a huge problem with crowd-control.
A secular approach to health care came with the Greeks, notably Hippocrates (460 to 377 BCE). The Hippocratics rejected prayers, spells and potions insisting on natural responses to disease: promoting rest, nutrition, healthy lifestyles and herbal supplements. The Hippocratic oath is a laudable declaration, albeit including some trade-guild protectionism. One sentence, “I will not use the knife, not even, verily, on sufferers from stone, but I will give place to such as are craftsmen therein”, fosters the separation of physicians from surgeons; a principle most relevant to this tale. The axiom “First do no harm” is not Hippocratic; it derives from a phrase used by Auguste Chomel (1788-1858), a Parisian pathologist, but we raise it here because it is important, if misattributed.
In The Aphorisms 1, the Hippocratics (there were more authors than Hippocrates) wrote 19 axioms on urine and they are shrewdly perceptive. “If a patient passes blood, pus, and scales, in the urine, and if it has a heavy smell, ulceration of the bladder is indicated” is a good evocation of cystitis and “When bubbles settle on the surface of the urine, they indicate disease of the kidneys, and that the complaint will be protracted” may describe the surface tension effects of proteinuria, a hallmark of nephritis, not UTI. These Greeks recognised the antiseptic properties of urine which they applied to burns and other skin lesions. Urine does indeed contain numerous antimicrobial substances, which we sabotage through dilution by recommending increased fluid intake when treating cystitis.
It was the Hippocratics, borrowing from the Sumerians and Babylonians, who fashioned the theory of the four humors: black bile, yellow bile, phlegm, and blood, with disease being attributed to an imbalance in these. The associated temperaments occur in common parlance; melancholic, choleric, phlegmatic and sanguine. These reflect our obsession with categories, which, as we shall see, is folly because biological systems abhor categorisation. Humorism came to dominate medical thinking, largely unchallenged, for the next 2000 years. Humoral thinking was adaptable, persuasive, mouldable to different circumstances and self-validating. Similarly today, plausible explanations, lacking empirical evidence, abound in medicine, so that imaginative invention, wrapped in jargon, is often used to answer inconvenient questions.
The medical superstar of the classical world was Galen; the Greek physician to the households of the emperors Marcus Aurelius, Commodus and Severus. He was a graduate of Pergamon and Alexandria, and a Hippocratic. Galen was a deeply studious man who had absorbed all of Greek medicine, including humorism. He was a disciplined anatomist, a teacher, prolific writer and a brilliantly effective surgeon. He understood the importance of cleanliness, sterility and disinfection, as well as the holistic Hippocratic principles of rest and nutrition. He emphasised the causes of disease over their effects. In a classical physiological experiment Galen demonstrated that urine was manufactured by the kidney. We should pity the poor primate that provided the evidence.
Galen’s achievements were extraordinary and his influence dominated the Middle Ages and Renaissance. Regrettably, he was too prolific for the transcribers of his writing so they penned abstractions that omitted many of his intellectual reflections. This precious, classical wisdom journeyed from the Greek scripts to Arabic texts of the Mediterranean Muslim culture, to Latin written in translation schools, particularly in Spain. This knowledge was modified through a scribal, transcription chain influenced by local opinion. These abstracts formed the core of university medieval medical education from the twelfth to the sixteenth century. Ultimately, the sophisticated scientific analyses of the Hippocratics and Galen were reduced to didactic recipes, foreshadowing modern-day guidelines.
Table 1.1. Herbal remedies for the urinary tract 2.
Linnaean taxonomyVernacular name
Urinary complaints
Agrimonia eupatoriaAgrimony
Arctium spp.Burdock
Arctostaphylos uva-ursiBearberry
Elytrigia repensCommon couch
Euphorbia spp.Spurge
Linum catharticumFairy flax
MalvaceaeMallow
Persicaria bistortaBistort
Pilosella officinarumMouse-ear hawkweed
Ruscus aculeatusButcher’s broom
Stellaria mediaChickweed
Vaccinium myrtillusBilberry
Veronica beccabungaBrooklime
Cystitis
Achillea millefoliumYarrow
From the fifth century, much health care was provided by the monastic hospitals. Hippocratic principles of cleanliness, rest and nutrition were combined with humorism through blood-letting and herbs. It might be hoped that a 1000 years of trial and error, with monastic knowledge exchanged through monastic networks, might have evolved a herbal grail, buried in some ancient library. The selection pressure was not very specific since the monks understood herbs to provide general humoral treatment, as was the view in folk practice. David Allen and Gabrielle Hatfield 2 spent 16 years documenting the herbal folk remedies of the British Isles and Table 1.1 describes their relevant data for the urinary tract. The vernacular names evoke magical powers; sadly, this is not to be.
Figure 1.1. Uroscopy fabricates the illusion of percipience — the sagacious physician contemplates the qualities of the urine and in applying his esoteric learning, discerns what is ailing the patient. Is this so different today when we dipstick and culture the urine? Illustration courtesy of Alex Wilby.
During the sixth century, Theophilus Protospatharius published a treatise De Urinis, which introduced the medieval world to Greek views on uroscopy ( Figure 1.1). Theophilus described a complex chromatic scale for thick and thin urine. He provided instructions on how to interpret appearances. De Urinis was a popular work being a source of pseudo sagacious knowledge for impressing clients. The matula, a bladder-shaped glass vessel specific to uroscopy, was a badge of expertise. Come the Renaissance, physicians were diagnosing by uroscopy alone, without taking a history or examining the patient as may happen today with a dipstick test or culture. Uroscopy provided lucrative opportunities for charlatans, some inventing uromancy for divination. Eventually, in 1637, Thomas Brian published Pisse Prophet which exposed this nonsense. Sadly, there were plenty of phonies ready to move in to replace uroscopy. Today, tests abound, few properly verified, and in later chapters we shall have long-overdue confrontations with urinalysis, urodynamics and cystoscopy. Beware! An investigation can be invented and used to define a disease, detectable only by the same investigation — it is a meaningless, self-validating imposter with urodynamics being an excellent example.
At the beginning of the eighteenth century, Antonie Philips van Leeuwenhoek, a Dutch draper and scientist, ground his own lenses to produce an effective, simple, single-lens microscope which he used to discover “animalcules”, which we understand to be microbes. The early compound microscopes, with two or more lenses, whilst increasing magnification, suffered from spherical and chr...

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