Michael Dillon - Profile on Academia.edu (original) (raw)

Papers by Michael Dillon

Archives of Disease in Childhood, Dec 1, 1983

A 5 month old boy died after fever, persistently raised blood pressure, and hypokalaemia. A disor... more A 5 month old boy died after fever, persistently raised blood pressure, and hypokalaemia. A disorder of cortisol metabolism caused by 11hydroxysteroid dehydrogenase deficiency was detected retrospectively. copyright.

Archives of Disease in Childhood, Dec 1, 1991

Archives of Disease in Childhood, Feb 1, 1991

We report 101 episodes of Kawasaki disease in 100 patients seen over a 12 year period. A total of... more We report 101 episodes of Kawasaki disease in 100 patients seen over a 12 year period. A total of 35 patients had cardiac involvement ranging from pericardial effusion to coronary artery aneurysms with ischaemic complications, which resulted in death in one patient. Laboratory investigations showed leucocytosis, thrombocytosis, and a raised erythrocyte sedimentation rate to be common features and the first two variables were significantly associated with cardiac involvement. Treatment regimens changed over the study period. Aspirin was used in most patients often in conjunction with dipyridamole and from 1986 intravenous immunoglobulin was given routinely to those patients seen early in the illness. Additional therapeutic measures in individual patients included prostacyclin, heparin, streptokinase, and plasma exchange/exchange transfusion. Attention is drawn to the uncertainty of the long term cardiovascular consequences in the light of adults reported with premature atherosclerotic lesions of similar appearance to those seen in Kawasaki disease.

Archives of Disease in Childhood, Jun 1, 1985

We report five children who presented with Raynaud's disease in whom we could find no clinical, h... more We report five children who presented with Raynaud's disease in whom we could find no clinical, haematological, or immunological evidence of a collagen disorder. Oral phenoxybenzamine proved useful for maintenance treatment in most, with infusions of prostacyclin, nitroprusside, and ketanserin during acute attacks.

Archives of Disease in Childhood, Oct 1, 1991

Four children (two boys and two girls) with hypoparathyroidism, renal insufficiency, and developm... more Four children (two boys and two girls) with hypoparathyroidism, renal insufficiency, and developmental delay are described. They were the products of consanguineous marriages in three related Asian families presenting over a six year period. AU the children died within the first 15 months of life despite treatment. Postmortem examination on one child showed absent parathyroid glands. We believe these children represent a previously undescribed syndrome that appears to be inherited in an autosomal recessive manner. Early onset idiopathic hypoparathyroidism is rare. It is usually a sporadic condition but familial forms have also been reported. It may occur in isolation or associated with other abnormalities. We report four children from three related families who presented in infancy with hypocalcaemia due to hypoparathyroidism. They also had evidence of renal insufficiency, failure to thrive, and developmental delay. This combination has not previously been described and appears to be inherited in an autosomal recessive manner.

The Journal of Clinical Endocrinology & Metabolism, 1999

Two heterozygous PTH/PTH-related peptide (PTHrP) receptor missense mutations were previously iden... more Two heterozygous PTH/PTH-related peptide (PTHrP) receptor missense mutations were previously identified in patients with Jansen's metaphyseal chondrodysplasia (JMC), a rare form of short limb dwarfism associated with hypercalcemia and normal or undetectable levels of PTH and PTHrP. Both mutations, H223R and T410P, resulted in constitutive activation of the cAMP signaling pathway and provided a plausible explanation for the abnormalities in skeletal development and mineral ion homeostasis. In the present study we analyzed genomic DNA from four additional sporadic cases with JMC to search for novel activating mutations in the PTH/PTHrP receptor, to determine the frequency of the two previously identified missense mutations, H223R and T410P, and to determine whether different mutations present with different severity of the disease. The H223R mutation was identified in three novel JMC patients and is, therefore, to date the most frequent cause of JMC. In the fourth patient, a novel

Archives of Disease in Childhood, Sep 1, 1983

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma fr... more Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that there may be at least 2 different pathogenetic mechanisms in epidemic and sporadic haemolytic uraemic syndrome and that the reduced PGI2 production observed in the sporadic type is due to an inhibitor of PGI2 production rather than a deficiency of stimulating factors. copyright.

BMJ, Nov 8, 1975

M J DILLON, MRCP, research fellow (present appointment: consultant physician, Hospital for Sick C... more M J DILLON, MRCP, research fellow (present appointment: consultant physician, Hospital for Sick Children, London WC1) JENNIFER M RYNESS, Bsc, biochemist other salt-wasting states. The findings emphasise the need to relate data from patients to age-matched control values before attempting interpretation and suggest that sodium depletion is a more potent stimulator of renin-aldosterone release than renovascular disease or renal scarring in children. Plasma renin-aldosterone profiles were also valuable in discriminating between renal and adrenal causes of salt loss in childhood.

Archives of Disease in Childhood, Sep 1, 1992

Between 1975 and 1985, 454 patients with hypertension were admitted to the Renal Unit of the Hosp... more Between 1975 and 1985, 454 patients with hypertension were admitted to the Renal Unit of the Hospital for Sick Children. A total of 110 (24%) patients presented with severely raised blood pressures deemed to require emergency management. At presentation 84/110 had symptoms and signs of long standing hypertension with neurological involvement. Between 1975 and 1980 bolus intravenous injections of diazoxide and/or hydralazine were used with the aim ofreducing the blood pressure to within the normal range for age in the first 12-24 hours after admission. Of 57 patients treated in this way 13 developed hypotensive complications and four, whose blood pressures returned to normal within 24 hours of admission, suffered irreversible neurological damage. Subsequently the management changed to the use ofintravenous infusions of labetalol (1-3 mg/kg/hour) and/or sodium nitroprusside (0-5-8 g/kg/min) to enable a more gradual controlled reduction of blood pressure over the first 96 hours of admission. Between 1980 and 1985, 53 patients were treated using this regimen. In all cases blood pressure reduction was achieved in a more controlled manner without further neurological impairment or serious irreversible side effects. From our experience, the use of labetalol and sodium nitroprusside by incremental infusion in the critical early phase of management has resulted in improved control of accelerated hypertension without the sudden hypotensive episodes seen when bolus injections are used.

British Journal of Ophthalmology, 1981

Four cases of anterior ischaemic optic neuropathy occurred in children with accelerated hypertens... more Four cases of anterior ischaemic optic neuropathy occurred in children with accelerated hypertension. The cause may have been a sudden relative fall in arterial pressure which reduced the perfusion of the optic disc, whose circulation was compromised by long-standing hypertensive vascular disease. The term anterior ischaemic optic neuropathy (AION) introduced by Hayrehl emphasises that ischaemic optic neuropathy is essentially a condition affecting the optic nerve head. In extensive studies on the blood supply to this region Hayreh and others2-4 have shown that the prelaminar portion of the optic nerve head and the peripapillary choroid are supplied on an approximately segmental basis from the posterior ciliary arteries. The intraocular distribution of these arteries, and particularly that to the optic nerve head and peripapillary choroid, is much more susceptible to obliteration through a fall in perfusion pressure than is the central retinal artery.5 6 AION is predominantly a disease of the elderly,7 and this is thought to reflect at least in part an inability to adjust to changes in perfusion pressure due to pre-existing vascular disease.8 9 Very few cases of AION have been reported in persons before late middle age. Pitcher and Curry'0 recently reported 2 cases of presumed ischaemic optic neuropathy in women of 30 and 32 years receiving treatment for malignant hypertension, and some details of 3 of our cases were recently published." This paper reports the occurrence of AION in 4 children with accelerated hypertension. Case reports CASE 1 An 11-year-old boy, was admitted to the Hospital for Sick Children,

Journal of the Tennessee Medical Association, 1975

The Journal of clinical endocrinology and metabolism, Jul 16, 2018

Five different activating PTH/PTHrP receptor (PTHR1) mutations have been reported as causes of Ja... more Five different activating PTH/PTHrP receptor (PTHR1) mutations have been reported as causes of Jansen metaphyseal chondrodysplasia (JMC), a rare disorder characterized by severe growth plate abnormalities and PTH-independent hypercalcemia. Assess the natural history of clinical and laboratory findings in twenty-four JMC patients and characterize the disease-causing mutant receptors in vitro. The H223R mutation occurred in 18 patients. T410P, I458R and I458K each occurred in single cases; T410R was present in a father and his two sons. Laboratory records were analyzed individually and in aggregate. Postnatal calcium levels were normal in most patients, but elevated between 0.15-10 years (11.8±1.37 mg/dL) and tended to normalize in adults (10.0±1.03 mg/dL). Mean phosphate levels were at the lower end of the age-specific normal ranges. Urinary calcium/creatinine (mg/mg) was consistently elevated (children: 0.80±0.40; adults: 0.28±0.19). Adult heights were well below the 3rd percentile ...

Current Paediatrics

Autoimmune diseases of children are on the whole, rare, but can be associated with not inconseque... more Autoimmune diseases of children are on the whole, rare, but can be associated with not inconsequential morbidity and mortality when they occur. Moreover, they pose major diagnostic and therapeutic challenges for the paediatrician, and the decision to treat such diseases with corticosteroids and in some instances cytotoxic immunosuppressant drugs must balance morbidity from the underlying disease against significant toxicity and injury from therapy. A number of novel therapies including anti-tumour necrosis alpha therapy, and monoclonal antibodies against B cells are beginning to be used in children, although their efficacy and safety remains to be fully elucidated.

Pediatr Nephrol 24 2225 2232, Jul 15, 2009

The clinical characteristics and outcomes of children with mid-aortic syndrome (MAS) and the effe... more The clinical characteristics and outcomes of children with mid-aortic syndrome (MAS) and the effectiveness of different therapeutic approaches in reducing hypertension are still debated. We conducted a single-centre retrospective review of the records of children with MAS over 30 years. Children with angiographic evidence of a narrowed abdominal aorta were included. Therapeutic approaches included medical management, percutaneous transluminal angioplasty and/or surgical intervention. Thirty-six children had presented at a median age of 2.7 years (10 days-10 years). Thirteen (36%) patients had associated syndromes, and 44% had been diagnosed with cerebrovascular disease. All patients had involvement of multiple arteries. The mortality rate was 8% after a median follow-up period of 4.5 (range 1.1-19.7) years. Among the children who survived, 90% had obtained a reduction in their blood pressure (BP). Of the patients, 76% had had a normal estimated glomerular filtration rate (eGFR) at the last follow-up examination. Seventeen percent (six of 36) had renal dysfunction at presentation. Although MAS is a severe and widespread disease, in most cases it can be effectively treated with a combination of medical, angioplasty and surgical interventions.

Eur J Pediat, 1994

The prevalence and antigen specificity of anti-neutrophil cytoplasmic antibodies (ANCA) in sera f... more The prevalence and antigen specificity of anti-neutrophil cytoplasmic antibodies (ANCA) in sera from 23 children with active systemic lupus erythematosus (SLE) were studied utilizing indirect immunofluorescence and IgG and IgM ELISA using crude neutrophil extract and purified proteinase 3, myeloperoxidase, lactoferrin, cathepsin G and elastase. ANCA were present in 69% of SLE children and consisted of IgM and IgG antibodies of variable specificities, but did not correlate with organ involvement or disease activity. It remains unclear whether they have pathogenic significance or are epiphenomena in the category of polyclonal B-cell activation. However, their presence is entirely compatible with SLE even though they have hitherto been commonly associated with other systemic vasculitides. Key words Systemic lupus erythematosus. Anti-neutrophil cytoplasmic antibodies 9 Cathepsin G Elastase Abbreviations ANCA antineutrophil cytoplasmic antibodies C-ANCA ANCA measured by IIF showing a cytoplasmic staining pattern 9 CATH cathepsin G CATH-IgG or IgM IgG or IgM ANCA reacting with cathepsin G CNE crude neutrophil extract 9 ELAS elastase 9 ELAS-IgG or IgM IgG or IgM ANCA reacting with elastase IIF indirect immunofluorescence microscopy 9 LACT lactoferrin LACT-IgG or IgM IgG or IgM ANCA reacting with lactoferrin MPO myeloperoxidase 9 MPO-IgG or IgM IgG or IgM ANCA reacting with myeloperoxidase-P-ANCA ANCA measured by IIF showing a perinuclear staining pattern 9 PR3 proteinase 3 9 PR3-IgG IgG ANCA reacting with proteinase 3 9 SLE systemic lupus erythematosus

Inherited disorders of sodium and water handling

In Johnson Rj and Feehally J Comprehensive Clinical Nephrology Mosby International London, 2000

Investigation and management of hypertension in children: a personal perspective

Pediatric Nephrology, 1987

The prevalence of hypertension in children is of the order of 1%-3%. Of these children, 10% will ... more The prevalence of hypertension in children is of the order of 1%-3%. Of these children, 10% will have severe hypertension and in the majority the increased blood pressure will be secondary to renal disease. Nephrologically orientated investigation is therefore important. The most helpful investigations are: peripheral plasma-renin activity, 99mTc dimercaptosuccinic acid (DMSA) scan, main and segmental renal vein renin measurements and renal angiography plus 123I metaiodobenzyl guanidine (MIBG) scan in suspected phaeochromocytoma. Drug treatment of accelerated hypertension is most successfully undertaken by intravenous labetalol or sodium nitroprusside; sustained moderate-to-severe hypertension by a beta-blocker plus a vasodilator or an angiotensin-converting enzyme inhibitor with or without a diuretic; mild hypertension by diet, diuretic and if necessary by more powerful hypotensives. Surgical treatment by revascularization or nephrectomy and percutaneous transluminal angioplasty can be successful. Utilizing the current range of investigational and therapeutic tools the aetiology and appropriate management of hypertension can be effectively and safely undertaken in the majority of hypertensive children.

Rare vasculitic syndromes : Special section: Paediatric rheumatology

Annals of Medicine, 1997

Pediat Nephrol, 1993

Renal tubular dysfunction in methylmalonic acidaemia

Eur J Pediat, 1991

Renal tubular function was assessed in seven patients with methylmalonic acidaemia not responsive... more Renal tubular function was assessed in seven patients with methylmalonic acidaemia not responsive to vitamin B12. Five patients failed to concentrate their urine normally and in these patients the glomerular filtration rate was also reduced. Fractional excretion of sodium was increased in four patients, fractional excretion of potassium in one patient and in three there was a decreased tubular reabsorption of phosphate. Although possibly representing primary tubular damage these findings were thought to be consistent with adaptive changes secondary to the reduced glomerular filtration rate. Two patients had evidence of a defect of urinary acidification and several had a degree of hyporeninaemic hypoaldosteronism suggesting type 4 renal tubular acidosis. In one patient with a mild variant no renal disease was detected. Decreased renal function and tubular abnormalities were common in patients with methylmalonic acidaemia. It is likely that they are linked and essentially secondary to the tubulo-interstitial nephritis that is histologically demonstrable on renal biopsy. The failure of urinary concentrating ability and the disturbed urine acidification will contribute to the metabolic derangement during episodes of decompensation.