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disorders including one of the two original patients described by Dent and
Friedman. Wrong had already been 'retired' for 6 years when this was published. It became clear that several similar clinical conditions were, on the basis of genetic analysis, the same as that which Wrong had originally termed 'Dent's Disease' in honour of his late mentor. This disease is variously termed
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in a quite different gene OCRL1. This gene had been identified earlier as mutated in patients with 'Lowe
Syndrome'. Wrong's discoveries had led to the identification of two new 'new' hereditary diseases, each based on one of Dent and Friedman's original patients, and one 'Dent Disease Type 1' due to CLCN5 mutation and the other, 'Dent Disease Type 2' due to OCRL1 mutation.
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41:(UCH), London. Though academic in his leanings, he was a compassionate physician who established a warm rapport with patients (though not with his students), a link he regarded as the keystone of his research. He belonged to a generation of idealistic young doctors responsible for the establishment of the UK's
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clinical syndrome very similar to that reported some 20 years earlier by Dent (his predecessor as
Professor of Medicine at UCH) and Friedman in 1964. Dent and Friedman originally reported two unrelated patients with the condition they termed 'Hypercalcuric Rickets' without identifying any hereditary
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made this paper a 'Citation
Classic'. Reviewing his time at Manchester, Wrong noted: 'I realise what an excellent education provided by giving me time to tackle my own problems under a benign yet critical supervision. Because of earlier marriage and the rigidity of our postgraduate medical training
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seven years earlier, was working on his final paper when admitted to
Intensive Care Unit at UCH, the hospital at which he had spent most of his professional life. The paper, published posthumously, describes a variant of autosomal dominant distal RTA, due to SLC4A1 mutations, originally found in SE
251:
Wrong's identification of Dent and
Friedman's second patient as having 'clinical' Dent Disease was expanded when, in 2005, Scheinman's group identified this patient and his family as having mutations not in CLCN5, the gene mutated in most of the families with Dent disease originally identified, but
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Wrong was unusual in the breadth of his medical interests. His 1981 reference book, The Large
Intestine: Its role in Mammalian Nutrition and Homeostasis, summarised research into a part of the human anatomy he felt was neglected due to unprofessional squeamishness on the part of the scientific
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inheritance. It was further shown that there were three forms of recessive RTA distinguished clinically and on the basis of molecular generics divided into disease due to SLC4A1 mutation and either the B1 or a4 subunits of the kidney H+-ATPase due to mutation of the ATP6V1B1 andATP6V0A4 genes
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A very similar hereditary clinical syndrome was reported by
Scheinman and colleagues. This clinical work was put on a very firm basis by Thakker, Scheinman and Wrong and colleagues who determined that mutation of the chloride channel gene CLCN5 was the cause of many, though not all, of these
181:. Furthermore, the paper identified a subset of patients with 'incomplete' RTA. In large part due to Wrong's work, it is now recognized that classical 'distal' or 'Type 1 RTA', due to the disease of the distal tubule, is only one form of the disease. 'Proximal' or 'Type 2 RTA' is another.
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Asia. In that final paper, Wrong presented a novel hypothesis to explain the frequency of the mutations in the tropics despite their adverse clinical effects. He suggested that changes in red cell metabolism might protect against malaria, a major killer in the region.
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respectively. Hereditary 'Proximal' or 'Type 2 RTA' may be caused by mutation of the SLC4A4 gene and yet a further 'Type 3 RTA' with combined features of proximal and distal RTA is due to mutation in the CA2 gene for carbonic anhydrase II. These developments in the
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in salt and water balance and developed much of his own experimental work into a short monograph published in 1981. However, it was his renal work, based initially on the urine acidification test which he developed with Davies, for which Wrong is best known.
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Wrong, OM; Norden AG; Feest TG (1994). "Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance".
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Wrong, OM; Norden AG; Feest TG (1994). "Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance".
219:'s hidden workings. These were rolled-up ribbons of semi-permeable tubing which could be eaten at breakfast and examined on retrieval distended with faecal fluid allowing comparison of gastrointestinal solute transport in normal subjects and those with
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establishment. "There is a curious reluctance in the medical profession to handle faeces," he said. He began a 1965 paper on the electrolyte content of human waste with the characteristically playful: "Stool is the
Cinderella of electrolyte studies."
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was a subject on which Wrong was an international expert and he wrote the relevant chapter on this subject for one of the standard nephrology textbooks. It is a summary of his experience of this finding based on almost his entire professional life.
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The original paper by Wrong and Davies examined the effect of the 'short ammonium chloride loading test' on acid excretion by the kidney. A key insight was that in the group of diseases termed 'Renal
Tubular Acidosis' (RTA), urinary excretion of
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At UCH over the following years, and following retirement in 1990, Wrong developed major insights into the physiology and pathophysiology of the human kidney. Wrong had a parallel interest in the role of the
109:
Oliver Wrong studied Medicine at Magdalen and completed his clinical studies at the Radcliffe Hospital, Oxford. His 'National Service' – military conscription - was spent with the Royal Army Medical Corps in
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component. Wrong, based on his own additional clinical work, discovered that this was a new hereditary disease and with his co-workers Norden and Feest reported it as a form of the renal 'Fanconi Syndrome'.
122:, he was appointed University Tutor in Medicine at Manchester Royal Infirmary. Leaf was a formative influence and an important paper was jointly produced on the role of Anti-Diuretic Hormone and the kidney.
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or Dent disease. Wrong's insights, which made this previously relatively neglected disease well-known, have prompted the suggestion that the disease should more properly be termed 'Dent-Wrong' disease.
36:
of the human kidney. Wrong himself contributed to much of the molecular work after his own "retirement". He dictated amendments to his final paper during his final illness in his own teaching hospital,
223:. Wrong manufactured 5,000 of these "bags" in his laboratory, and while colleagues and family members were recruited as experimental subjects, he swallowed most of them himself.
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118:. This was a geographical region to which he would return several times in his research. After internships in Toronto and at Massachusetts General Hospital with
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programme, few of our present graduates feel able to afford such self indulgence'. After an appointment at UCH, Wrong became senior lecturer in medicine at the
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85:, A.L. Smith. Murray died of heart disease at the age of 38 and Oliver wrote an account of his father's illness, including consultations with
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The identification of several hereditary forms of RTA was developed by Wrong and co-workers and forms the basis of many of the advances of
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In a major medical insight, Wrong realised that a number of the patients he was seeing in one of his clinics at UCH had an apparently
32:, he made detailed clinical observations and scientifically imaginative connections which were the basis of numerous advances in the
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and Rosalind Smith. Murray Wrong was a history lecturer and later vice-president of Magdalen, and his own father was the historian
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A great believer in self-experimentation, Wrong invented the "Wrong bags", which allow precious "in vivo" insights into the
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Lloyd, SE; Pearce SH; Fisher SE; et al. (1996). "A common molecular basis for three inherited kidney stone diseases".
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in this area. By rigorous phenotypic classification, Wrong and other workers showed that 'Type 1 RTA' could have either
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specialist) and one of the founders of the speciality in the United Kingdom. From a background as a "salt and water"
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of the kidney may be traced back in large part, though not exclusively, to Wrong's original 1959 paper.
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with two of his sisters and was raised by his grandfather, George MacKinnon Wrong. Another sister was
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Oliver Wrong married Marilda Musacchio, a primary school teacher from the
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led to a split in the upbringing of the six children. Oliver was sent to
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was relatively well preserved. This was unlike the situation in chronic
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Wrong, O; Davies HE (1959). "The excretion of acid in renal disease".
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Wrong, O; Davies HE (1959). "The excretion of acid in renal disease".
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The large intestine: its role in mammalian nutrition and homeostasis
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Hoopes, RR Jr.; Shrimpton AE; Knohl SJ; et al. (2005).
759:"Hypercalcuric Rickets Associated With Renal Tubular Damage"
138:. His clinical analysis of this process and the impact of
577:"Back to the future: renal tubular acidosis then and now"
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in 1969 and a return to UCH in 1972 to succeed Professor
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Khositseth, S; Bruce LJ; Walsh SB; et al. (2012).
808:"X-linked recessive nephrolithiasis with renal failure"
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Khositseth, S; Bruce LJ; Walsh SB; et al. (2012).
693:. Oxford: Oxford University Press. pp. 1257–1280.
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Fry, AC; Karet FE (2007). "Inherited renal acidoses".
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Fry, AC; Karet FE (2007). "Inherited renal acidoses".
1053:"Wellcome Library Western Manuscripts and Archives"
704:Wrong, Oliver M.; CJ Edmonds; VS Chadwick (1981).
533:Wrong, O (1978). "This Week's Citation Classic".
518:Wrong, O (1978). "This Week's Citation Classic".
442:Leaf, A; Bartter FC; Santos RF; Wrong O (1953).
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