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M J Dillon

Publications and source records attributed to M J Dillon.

At least 91 records · Page 5Linked to original sources
PubMed1993

Tissue resistance to 1,25-dihydroxyvitamin D without a mutation of the vitamin D receptor gene.

OBJECTIVE: Hereditary vitamin D resistant rickets (HVDRR) is characterized by severe rickets and is often accompanied by alopecia. Mutations in the gene encoding the vitamin D receptor have been found in this condition. In a patient with the characteristic phenotype we have investigated the functional defect and sequenced the gene to seek a mutation. DESIGN: Patient and control cell lines prepared from skin fibroblasts and peripheral blood lymphocytes were used to measure binding of 1,25(OH)2D3 and to isolate vitamin D receptor mRNA. VDR cDNA was sequenced and transfected into receptor defective cells. PATIENT: A child with alopecia diagnosed as having rickets due to resistance to 1,25(OH)2D3. MEASUREMENTS: Cytosolic binding and nuclear association of 1,25(OH)2D3 were determined in patient and control cells, and functional response to 1,25(OH)2D3 assessed by measurement of 24-hydroxylase activity. VDR mRNA was prepared, reverse transcribed, and cDNA sequenced. VDR cDNA was also transfected into VDR-deficient CV-1 cells and functional response to 1,25(OH)2D3 assessed by co-transfection with a chloramphenicol acetyltransferase (CAT) reporter plasmid. RESULTS: VDR from the patient were able to bind 1,25(OH)2D3 but showed no nuclear localization resulting in an absence of functional response to 1,25(OH)2D3. Sequencing revealed that the VDR coding region was normal. Expression studies of the patient's VDR showed functionally normal VDR as evidenced by normal transactivation in the presence of 1,25(OH)2D3. CONCLUSION: These data indicate a new cause of tissue resistance to 1,25(OH)2D3 which occurs in the absence of mutations in the coding region of VDR gene and which is characterized by defective nuclear localization of this receptor.

Alopecia↗
PubMed1993

Sodium-lithium countertransport and family history of hypertension in childhood.

We have studied the relationship between sodium-lithium countertransport, determined in childhood, and family history of hypertension. Countertransport was measured in healthy children and those with secondary hypertension. There was no significant difference in countertransport between these two groups. In the normal children (n = 52, median age 6.8 years), there was a positive relationship between body mass index and countertransport (rs = 0.34, p < 0.02). A positive relationship between family history of hypertension using a ranked scoring system, and countertransport, not related to age, body mass or blood pressure (n = 34, rs = 0.63, p < 0.001) was also found. There was no significant relationship between intracellular sodium concentration and countertransport. These data confirm that countertransport in normal children is related to body mass index and indicate that a genetic predisposition to primary hypertension marked by sodium-lithium countertransport is identifiable in childhood.

Adolescent↗
PubMed1993

Cystic fibrosis presenting as kwashiorkor with florid skin rash.

Two infants with a florid erythematous rash and generalised oedema, hypoalbuminaemia, and anaemia were found to have cystic fibrosis. This rare presentation is associated with false negative sweat tests, delays in diagnosis, and a considerable mortality. It is proposed that this presentation represents a manifestation of kwashiorkor secondary to malabsorption. The recognition that these infants have kwashiorkor provides some insight into the pathogenesis and management of their illness.

Cystic Fibrosis↗
PubMed1993

Tubular proteinuria in steroid sensitive multi-relapsing nephrotic syndrome.

The urinary excretion of N-acetyl-beta-D-glucosaminidase (UNAG) and retinol binding protein (URBP) was studied in 65 children with steroid sensitive multirelapsing nephrotic syndrome (MRNS): 28 on cyclosporin A (CyA) therapy, 22 on prednisolone (P), 15 off-treatment and in 32 normal children to assess renal tubular damage or dysfunction. The urinary protein excretion was expressed in relation to that of creatinine (UNAG/UC in mumol pnp/h/mmol; URBP/UC in microgram/mmol). There was a weak but significantly negative correlation between age and both, UNAG/UC (r = -0.38, p < 0.01) and URBP/UC (r = -0.50, p < 0.05) in normal children, but not in nephrotics. In normals and in patients off steroids an association between these two proteins was found (r = 0.38, p < 0.05; r = 0.56, p < 0.05 respectively). Geometric mean UNAG/UC was significantly higher in nephrotics on CyA therapy (26.5 +/- 4.0), and on P (37.0 +/- 7.9) as well as in those off-treatment (16.3 +/- 3.1) compared to normal children (9.3 +/- 3.4). There was a further increase in those with raised urinary albumin: creatinine ratio (UA/UC) (> 0.1 mg/mg). URBP/UC was not increased in any of the groups of children with MRNS. Raised NAG in urine may therefore indicate active nephrotic syndrome rather than being due to the drug therapy.

Acetylglucosaminidase↗
PubMed1992

Neutrophil activation in the haemolytic uraemic syndrome: free and complexed elastase in plasma.

There is evidence of neutrophil involvement in the pathogenesis of the haemolytic uraemic syndrome (HUS), and neutrophil release products are thought to cause endothelial cell damage. Elastase is the major lysosomal proteinase liberated by activated neutrophils. In this study we measured both free and complexed elastase. No free elastase activity could be detected in the plasma of patients with diarrhoea-associated (D+) HUS using a specific substrate. However, there was a marked increase in alpha 1-antitrypsin (alpha 1-AT) complexed elastase as measured by a newly developed enzyme-linked immunosorbent assay not only in D+ HUS, but also in non-diarrhoea-associated (D-) HUS. This finding is independent of either a high polymorphonuclear leucocyte count or renal failure. This increase in bound elastase together with our sequential data which demonstrate raised alpha 1-AT complexed elastase levels early in the disease process further support the theory that neutrophil activation is one of the key events in the pathophysiology of this disorder.

Adult↗
PubMed1992

Cadaveric renal transplantation in children under 5 years of age.

From March 1987 to August 1990 23 cadaveric renal transplants were performed in 19 children under the age of 5 years at the time of transplantation. The mean age of the recipients was 3.3 years (range 1.3-4.7) and the mean weight 13.0 kg (range 9.3-19.2). The mean donor age was 7.8 years (range 1.5-25). All children received triple immunosuppression with prednisolone, cyclosporin A and azathioprine, and 4 who had 2 grafts during this period also received antithymocyte globulin at the time of the second transplant. Patient survival is 100%. Actuarial first cadaveric graft survival was 57% at 1 year and remains unchanged at 3 years. There were 10 graft losses, 4 were associated with renal venous thrombosis without apparent rejection. Two were lost due to acute vascular rejection with associated renal venous thrombosis, and the remaining 4 losses followed cellular or chronic vascular rejection. The mean glomerular filtration rate +/- SD was 51.4 +/- 23.6 ml/min per 1.73 m2 (n = 11) at 1 year and 43.5 +/- 25.3 at 2 years (n = 6). The mean height standard deviation score improved from -2.2 +/- 1.1 at the time of transplantation to -1.3 +/- 1.0 1 year post transplant (n = 11). The immunosuppression was well tolerated with a low incidence of side effects. Cadaveric renal transplantation remains a difficult but rewarding undertaking in children under 5 years of age.

Age Factors↗
PubMed1992

Crescentic glomerulonephritis in children.

Data on patients with crescentic glomerulonephritis (greater than 50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7-15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR less than 30 ml/min per 1.73 m2) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%-79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m2. In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P less than 0.05). Outcome was not, however, related to the percentage of glomeruli affected (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5.

We report two unusual cases in which mesangiocapillary glomerulonephritis occurred in association with meningococcal infection. C3 nephritic factor, an autoantibody to alternate pathway C3 convertase, was present. Low serum complement C3 and C5 levels were also noted. The depressed complement levels, in conjunction with terminal complement complexes at the upper limit of normal, suggest activation of the early and late complement cascade. We suggest that children presenting with meningococcal infection should have a regular urine examination, as well as full complement measurements performed, in view of the association with hypocomplementaemic mesangiocapillary glomerulonephritis. Similarly, prophylactic penicillin should be prescribed for patients with mesangiocapillary glomerulonephritis and persistently low C5 levels to prevent meningococcal complications.

Adolescent↗
PubMed1992

Renovascular disease in childhood.

Fifty-four children referred for investigation of hypertension had renovascular disease. In eight patients it was associated with neurofibromatosis, in three with idiopathic hypercalcemia of infancy, and in five cases it followed an arteritic illness. Fibromuscular dysplasia was the underlying abnormality in the majority of cases (46%). Twenty-six patients (48%) were first seen with accelerated hypertension; 38 children (70%) had bilateral renal arterial disease, and in 41 (76%), disease of the small intrarenal vessels was found. Renal vein renin ratios indicated unilateral disease in 31 cases; the results correlated with arteriography findings in 32 (62%) of 51 patients. Eleven children also had the middle aortic syndrome, and 9 of 16 patients, investigated by cerebral arteriography because of cranial bruits or focal neurologic signs, had cerebral vascular abnormalities. Twenty patients were treated surgically--10 by reconstructive procedures, 11 by nephrectomy or heminephrectomy, and 6 by transluminal angioplasty. Of these, 9 (45%) are normotensive with no treatment, 10 have a decreased requirement for antihypertensive drugs, and 1 had no improvement. Thirty-four patients were treated medically because of the extent of their disease; two patients have died of hypertensive complications. We conclude that renal vascular disease in children is often widespread, may be associated with intracerebral vascular disease, frequently affects both kidneys, including both intrarenal and extrarenal vessels, and is therefore not always amenable to surgical intervention and cure.

Adolescent↗
PubMed1992

Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood.

Polymorphoneutrophil leucocytes (PMNLs) are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D+ HUS). We investigated mechanisms of PMNL involvement by measuring tumor necrosis factor alpha (TNF alpha) and the novel cytokine, interleukin-8 (IL-8), a potent activator of neutrophils, together with alpha 1- antitrypsin-complexed elastase (alpha 1-AT-E) as a marker of neutrophil degranulation, and anti-neutrophil cytoplasmic antibodies (ANCA). IL-8 was not detected in the 17 normal children, but was significantly elevated in 20 of 25 D+ HUS children (P less than 0.005), and in three of nine children with non-diarrhea-associated (D-) HUS. Sequential data showed that IL-8 peaked transiently in the circulation, reaching a maximum just before a more protracted burst of alpha 1-AT-E. The IL-8 levels correlated significantly with circulating alpha 1-AT-E concentrations (r = 0.50, P less than 0.05). In D+ HUS IL-8 levels also correlated with the PMNL count (r = 0.63, P less than 0.005), and the highest values were seen in those children who died in the acute phase of the disease. TNF alpha was raised in only 1 of 16 D+ HUS children and in no patients were ANCA detected. The data suggest that PMNLs in HUS are recruited by IL-8, that this cytokine plays a key role in the PMNL activation which occurs, and that agents which suppress this recruitment and activation might play a therapeutic role in this disorder.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

A measles virus isolate from a child with Kawasaki disease: sequence comparison with contemporaneous isolates from 'classical' cases.

We examined the relationship between a measles virus isolate from a child with Kawasaki disease and two contemporaneous wild-type isolates from children with 'classical' measles and the Schwarz vaccine strain. Sequence analysis of 3118 bp from the nucleoprotein, matrix, fusion and haemagglutinin genes of each virus revealed that the isolate from the child with Kawasaki disease was not related to measles vaccine strains and did not contain any of the marked abnormalities previously found in subacute sclerosing panencephalitis isolates, but was more akin to wild-type isolates currently circulating in the U.K. A comparison of our sequences with those obtained from earlier wild-type U.K. isolates suggests significant evolution of measles virus in the U.K. over the last decade.

Amino Acid Sequence↗
PubMed1992

Management of hypertensive emergencies.

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 of reducing 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 of intravenous infusions of labetalol (1-3 mg/kg/hour) and/or sodium nitroprusside (0.5-8 micrograms/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.

Adolescent↗
PubMed1991

Long term renal outcome of childhood haemolytic uraemic syndrome.

OBJECTIVE: To evaluate the long term outcome of renal function in infants and children after diarrhoea associated haemolytic uraemic syndrome. SETTING: The Hospital for Sick Children, Great Ormond Street, and the Royal Free Hospital, London. SUBJECTS: 103 children with the syndrome who presented between 1966 and 1985; 88 attended for follow up investigations (40 male, 48 female) with a mean age 11.6 (range 5.2-22.6) years and a mean duration of follow up of 8.5 (range 5.1-21.3) years. MAIN OUTCOME MEASURES: Blood pressure, ratio of early morning urine albumin to creatinine concentration, glomerular filtration rate, and plasma renin activity. RESULTS: The mean (SD) systolic blood pressure standard deviation score was 0.38 (0.67) and diastolic blood pressure SD score was 0.10 (0.76). The geometric mean ratio of overnight urine albumin to creatinine concentration was 1.27 (range 0.03-48.2), significantly higher than the value observed in 77 normal children (0.32 (0.05-1.95), p less than 0.0001). Glomerular filtration rate estimated from the plasma clearance of chromium-51 EDTA was 95.1 (22.7) ml/min/1.73 m2 surface area, and 16 children had a rate of less than or equal to 80 ml/min/1.73 m2. Significant negative correlations were found between glomerular filtration rate and urinary albumin to creatinine ratio (r = -0.41, p less than 0.0001) and glomerular filtration rate and systolic blood pressure SD score (r = -0.48, p less than 0.0001). A significant positive correlation was found between urinary albumin to creatinine ratio and systolic blood pressure SD score (r = 0.25, p = 0.02). CONCLUSIONS: After an acute episode of diarrhoea associated haemolytic uraemic syndrome 31% (27/88) of children had an increased albumin excretion, 18% (16/88) had a reduced glomerular filtration rate and 10% (9/88) had both, in association with a higher systolic blood pressure, indicating considerable residual nephropathy in this group.

Adolescent↗
PubMed1991

Anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies.

Anti-neutrophil cytosolic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) have been identified in a wide variety of disorders, but their pathophysiological role remains unclear. ANCA appear to be particularly associated with various forms of vasculitis including Wegener's granulomatosis. Kawasaki disease and microscopic polyarteritis. Cytoplasmic staining (cANCA) on indirect immunofluorescence is associated with extrarenal disease and a perinuclear pattern (pANCA) with renal limited disease. The cANCA antigen appears to be proteinase 3 and that for pANCA myeloperoxidase. AECA have been detected in systemic lupus erythematosus, scleroderma and dermatomyositis but are also found in systemic vasculitis, Kawasaki disease, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura and renal allograft recipients at the time of rejection. Their presence appears to be correlated with disease activity and they may be directed against epitopes on as yet unidentified infective agents that precipitate some of the diseases in which they are found that cross-react with antigenic sites exposed on endothelial cells. Measurement of these antibodies has a diagnostic role, facilitates monitoring of disease activity and may prove valuable in understanding the pathogenesis of the diseases in which they are found.

Autoantibodies↗
PubMed1991

Renal tubular dysfunction in methylmalonic acidaemia.

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.

Acidosis, Renal Tubular↗
PubMed1991

Autosomal recessive hypoparathyroidism with renal insufficiency and developmental delay.

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. All 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.

Child, Preschool↗