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M J Dillon

Publications and source records attributed to M J Dillon.

At least 73 records · Page 4Linked to original sources
PubMed1995

Anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies are not increased in Kawasaki disease.

We studied anti-neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) in 58 children with acute Kawasaki disease (KD) before i.v. gamma globulin treatment, 35 children with infection and fever > 38.5 degrees C, and 48 healthy afebrile children. ANCA were studied by indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and by ELISA with crude neutrophil extract as antigen. AECA were studied using ELISA on resting and activated endothelial cells. ANCA IIF was weakly positive, cytoplasmic, diffuse and homogeneous in all three groups. ANCA IIF, ANCA ELISA and AECA ELISA were no higher in KD than in febrile children. There was no difference between KD with and KD without coronary artery aneurysms. AECA differences between the KD and afebrile group were not significant after correction for total IgM. In contrast with our previous findings, we conclude that ANCA and AECA are not raised in KD compared with febrile controls. It therefore seems unlikely that they are important in the pathogenesis of vasculitis in KD.

Adolescent↗
PubMed1995

Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease.

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.

Adolescent↗
PubMed1995

Sodium-lithium countertransport in children with diabetes and their families.

Abnormalities of sodium-lithium countertransport have been extensively implicated in adult primary hypertension and a relationship between sodium-lithium countertransport and family history of hypertension in children has been previously found. More recently it has been suggested that increased sodium-lithium countertransport may play a part in the pathogenesis of nephropathy in insulin dependent diabetes mellitus (IDDM). Children and adolescents with IDDM and their family members were studied. In those with IDDM (n = 36, median age 14.6 years, range 9.5-19.2 years) there was no relationship between sodium-lithium countertransport (range 0.098-0.585 mmol/l red blood cells/hour) and age, blood pressure as expressed by systolic or diastolic SD scores, glycated haemoglobin, serum lipids, or intracellular sodium concentration. A positive relationship (rs = 0.44) was found between sodium-lithium countertransport and early morning urinary albumin to urinary creatinine ratio (UA/UC), expressed as the logarithm of the geometric mean of two consecutive samples, for each individual (range 0.4-22 mg/mmol). Sodium-lithium countertransport was increased in those with IDDM compared with their non-diabetic siblings, in a paired analysis (n = 26). There was no relationship between UA/UC in the children with diabetes and sodium-lithium countertransport in their parents. These studies in this population of diabetic children indicate that increased sodium-lithium countertransport may play a part in the early stages of the development of nephropathy in IDDM.

Adolescent↗
PubMed1995

Random zero sphygmomanometer versus automatic oscillometric blood pressure monitor; is either the instrument of choice?

The Hawksley random zero sphygmomanometer was designed to eliminate observer bias and two digit preference. We have measured blood pressure (BP) in a group of 62 young adults (median age 26.1 years, range 20.2-31.3 years) with reflux nephropathy under standardised conditions (that is, in the morning, after a 2 h supine rest, before venepuncture, using a standard 12 x 23 cm adult size cuff appropriate for the machine used) utilising the random zero sphygmomanometer and the automatic oscillometric BP monitor (Dinamap 8100, Critikon). Seven consecutive recordings of right brachial BP at intervals of 2 min were taken using each instrument alternatively, and the first reading was discarded. The first instrument used to measure BP was alternated between patients to eliminate bias on instrument preference. Random zero sphygmomanometer was used as recommended by the manufacturers and Korotkoff phase V was used to measure the DBP. The observer and the equipment used were the same throughout the study period. The mean SBP and DBP were calculated to the nearest 1 mm Hg utilising the three recordings taken by each instrument. The limits of agreement and the repeatability coefficients for each method of measurement were assessed utilising the statistical method described by Bland and Altman in 1986. The correlation coefficients among random zero and automatic oscillometric BP monitor for SBP and DBP measurements were 0.84 and 0.67, respectively. The average BP (mean of random zero and automatic oscillometric BP monitor measurement) plotted against the difference between the two methods of measurement showed no relation between the difference and the average of measurement in the ranges of BP studied, that is, between 100 and 160 mm Hg systolic and 55 and 100 mm Hg diastolic. The mean of difference between random zero and automatic oscillometric BP monitor for SBP was -6.45 (s.d. 6.07) and for DBP +10.77 (s.d. 8.16) mm Hg. The limit of agreement for SBP measurement was +5.69 to -18.59 mm Hg and for DBP was +27.09 to -5.55. The repeatability coefficients of random zero and automatic oscillometric BP monitor for systolic and diastolic measurements were 8.64 and 7.04, and 9.72 and 6.62, respectively. Bland and Altman analysis indicates major differences between the two methods of measurement. The automatic oscillometric BP monitor could on average over-read the systolic by 6.45 mm Hg and under-read the diastolic by 10.77 mm Hg compared with that of random zero. Furthermore, the limits of agreement were wide enough for a normotensive to be inadvertently defined as a hypertensive on machine error alone. This clearly indicates that automatic oscillometric BP monitor and random zero BP measurements cannot be used interchangeably in clinical practice. Furthermore, the repeatability coefficients, which should ideally be zero, are too large for either instrument to be considered as the gold standard for BP measurement, although that of automatic oscillometric BP monitor was superior to that of random zero. This study highlights the importance of using nomograms generated by the same method of measurement for comparison both in paediatric and adult practice for correct interpretation of BP.

Adult↗
PubMed1995

Vasculitis in children and adolescents.

Vasculitis can present in childhood. There is a wide spectrum of disease in vasculitis, with Henoch-Schönlein purpura and Kawasaki disease occurring most commonly; however, macroscopic and microscopic polyarteritis, Wegener's granulomatosis, Takayasu's disease, cutaneous polyarteritis, hypersensitivity angiitis; vasculitis associated with connective tissue disorders, such as dermatomyositis, and a number of other miscellaneous vasculitides are seen. With the current range of investigative and therapeutic tools, it is possible to diagnose and treat the majority of patients although morbidity and mortality is not inconsequential.

Adolescent↗
PubMed1995

Bartter's syndrome associated with severe retinopathy and presenting as pseudohypoaldosteronism in a newborn.

Various pathophysiological explanations for Bartter's syndrome have been put forward since the condition was first described in 1962. It is currently thought that reduced reabsorption of sodium chloride in the distal tubule of the loop of Henle and the collecting ducts leads to secondary hyperkaluria and hypokalaemic metabolic alkalosis. We describe a 9 1/2-year-old boy with Bartter's syndrome and severe retinopathy whose features may be those of a previously unrecognized disorder.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Long-term cyclosporin A treatment of minimal-change nephrotic syndrome of childhood.

We evaluated the efficacy of long-term cyclosporin A (CyA) treatment in the maintenance of remission in 40 children with steroid-dependent minimal-change nephrotic syndrome (MCNS). CyA was given in an initial dose of 5 mg/kg per day, adjusted to maintain a trough whole blood level of 50-150 ng/ml. All the 40 children received CyA for 1 year. In 18 patients, CyA was continued for a further period of at least a year without interruption; 9 patients had a second course of CyA therapy after an interval of at least 1 month. Of the 40 children 29 (72%) had one or more relapses during treatment with CyA, with 16 (40%) relapsing during the 1st year. During the second period of CyA, 10 (56%) of the 18 children treated continuously relapsed, whereas all the 9 children who had an interrupted course of therapy relapsed. CyA was discontinued at one time in 27 patients, all of whom subsequently relapsed, with a median time to relapse of 26 days. Long-term prednisolone in addition to CyA was required to maintain remission in 16 (40%) of the whole group. The results suggest that the long-term use of CyA is able to maintain remission of MCNS, although 40% of the patients also required low-dose alternate-day steroids; patients appeared to fare worse if the CyA course was interrupted; no patient experienced a long-term remission after CyA was stopped.

Adolescent↗
PubMed1994

Effect of cyclosporin A on glomerular filtration rate in children with minimal change nephrotic syndrome.

Cyclosporin A (CyA) is now commonly used in the management of children with steroid-dependent nephrotic syndrome. In order to assess nephrotoxicity related to CyA therapy, we measured glomerular filtration rate (GFR) on 123 occasions in 24 children with minimal change nephrotic syndrome receiving CyA. GFR was estimated from the plasma clearance of 51chromium-EDTA every 3 months during CyA therapy of up to 27 months duration. There was a significant reduction in GFR after 3 months of CyA therapy [118 +/- 33 (SD) to 93 +/- 24 ml/min per 1.73 m2] but no further fall thereafter, although the reduction in GFR was sustained for the duration of CyA therapy. This reduction in GFR appeared to be reversible upon cessation of CyA, but careful monitoring of renal function is necessary in such patients to prevent the development of longer term nephrotoxic sequelae.

Adolescent↗
PubMed1994

Serum intact parathyroid hormone and ionised calcium concentration in children with renal insufficiency.

We report our experience of the use of an immunoradiometric assay for intact parathyroid hormone (i-PTH) and the measurement of plasma ionised calcium concentration (PCa2+) in 73 children with chronic renal insufficiency (CRI); plasma creatinine concentration (PCr) 52-856 mumol/l. There was a poor correlation between i-PTH and PCr (r = 0.10, n = 552) compared with that for C-terminal PTH and PCr (r = 0.60, n = 248), suggesting that the i-PTH assay is independent of renal function in this group of treated children. A clear response of i-PTH to a low total plasma Ca (tPCa) and PCa2+ was observed. There was a significant positive correlation between both tPCa and PCa2+ (r = 0.50, n = 389) and the fraction of Ca2+ (the fraction of tCa which was ionised) and PCa2+ (r = 0.50, n = 389). The finding of a low or normal PCa2+ with a low calculated fraction of Ca2+ was frequently observed, i.e. the measured tPCa was unexpectedly high, suggesting complexing of Ca2+ by accumulated anions in CRI. There was a poor relationship between the plasma albumin concentration and both bound plus complexed Ca (tPCa minus PCa2+) and the fraction of Ca2+ (r = 0.15 and -0.17, respectively). The positive predictive value for a raised i-PTH of a tubular reabsorption of phosphate of less than 80% was 0.87, and of an alkaline phosphatase greater than 800 U/l was 0.37.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome.

Abnormal T lymphocyte function and reduced interleukin-2 (IL-2) production have been implicated in the pathogenesis of the nephrotic syndrome (NS). We investigated: (1) lymphocyte subpopulations and expression of IL-2 receptor (IL-2R) on T cells using two-colour flow cytometry, (2) serum IL-2 and (3) the soluble component of IL-2R (sIL-2R) in serum, using enzyme-linked immunosorbent assay, in 38 children with NS. All children, except those in remission, had marked proteinuria. They were divided into groups according to renal pathology: (1) steroid-sensitive NS (SSNS) not receiving prednisolone therapy, (2) SSNS on prednisolone, (3) focal segmental glomerulosclerosis (FSGS), (4) SSNS in remission and not receiving prednisolone therapy, (5) congenital NS (CNS). Results were compared with 26 age-matched controls. Total T lymphocytes (CD3) were reduced in groups 1 and 2; CD4 count was reduced in groups 1-4; CD8 count increased in groups 2 and 3; CD8 and CD19 (B lymphocytes) were significantly reduced in group 5. Increased IL-2R expression (CD25) on CD4 lymphocytes was noted in groups 1, 2 and 3 implying activation of these cells. In patients with SSNS, increased serum sIL-2R was recorded during relapse (1,273 +/- 497 U/l vs. 913 +/- 401 U/l in remission, P < 0.005) but free serum IL-2 was not detectable at any stage. The specific alterations in lymphocyte subpopulations in SSNS and FSGS would imply an involvement of the immune system distinct from that in CNS.

Acute Disease↗
PubMed1994

Antiendothelial cell antibodies can be cytotoxic to endothelial cells without cytokine pre-stimulation and correlate with ELISA antibody measurement in Kawasaki disease.

To confirm the presence of antiendothelial cell antibodies (AECA) and study the clinical value of their measurement in Kawasaki disease (KD), sera from patients with KD were assessed for binding to human umbilical vein endothelial cells (HUVEC) using a cellular based ELISA, and for complement-mediated cytotoxicity using 111In-labelled HUVEC. In the ELISA assay, IgM AECA were detected in 16/22 sera, whereas IgG AECA were only present in one out of 19 sera. There was a significant difference in IgM AECA titres when comparing patients with controls. Eight out of 16 sera showed cytotoxicity against HUVEC, and this was significantly enhanced when HUVEC were pretreated with tumour necrosis factor (TNF). IgM AECA titres measured by ELISA were positively correlated with their cytotoxicity. The findings suggest that IgM class AECA in sera from patients with KD are detectable by ELISA method, and that some of these antibodies, 50% in this study, can mediate complement-dependent cytotoxicity against endothelial cells.

Adolescent↗
PubMed1994

Alternative treatment to corticosteroids in steroid sensitive idiopathic nephrotic syndrome.

A review was undertaken of the use of alternative immunosuppressive treatment in addition to corticosteroids in a cohort of 429 children with steroid sensitive nephrotic syndrome (SSNS) treated between 1980 and 1994. Two hundred and twenty two children (52%) received at least one course of alternative treatment, 98 (23%) two, and 43 (10%) three. Cyclophosphamide was administered to 196 children (46%); in 181 it was the first course of alternative treatment and in 104 (57%) of those it was also the last ('final course'). Levamisole was given to 56 children (13%) and cyclosporin to 53 (12%). Fifteen children in whom cyclosporin failed were treated with chlorambucil. A few patients received azathioprine or vincristine. Ten children developed secondary steroid resistance, of whom five progressed to chronic renal failure. Acute complications included reversible renal failure, septicaemia, peritonitis, convulsions, and cerebral thrombosis. There were three deaths. It is concluded that half of the referred children with SSNS were deemed to require at least one course of alternative immunosuppressive treatment, and that side effects of the treatment and complications of SSNS are infrequent but occasionally fatal.

Adrenal Cortex Hormones↗
PubMed1994

Renovascular hypertension.

Renovascular disease constitutes approximately 10% of cases of secondary hypertension in childhood. It is associated with neurofibromatosis and a number of other syndromes. Fibromuscular dysplasia is the commonest histopathological finding. Bilateral and intrarenal disease is common and is associated with extrarenal arterial disease in a significant proportion of cases. Utilizing currently available investigative procedures, the nature of the disease can be defined and decisions made regarding appropriate treatment. However, although there is the potential for surgical cure, a substantial number of children still require medical therapy probably due to the high incidence of bilateral and small intrarenal arterial involvement that is not amenable to surgical or angioplasty treatment.

Aneurysm↗
PubMed1993

Atypical (non-diarrhea-associated) hemolytic-uremic syndrome in childhood.

We describe the clinical and laboratory features of 20 children who were seen during the past 20 years with idiopathic nondiarrhea-associated hemolytic-uremic syndrome. There was no seasonal variation in time of onset; a genetic pre-disposition seemed likely in two of the cases. The prodromal illness was nonspecific and by definition did not include diarrhea. Hypertension was a major problem in the majority of the patients. Five died, three during the initial illness; four are in end-stage renal failure, and all but two of the survivors have residual nephropathy. Eleven patients had a "relapsing" course; up to eight additional documented episodes of hemolytic-uremic syndrome occurred in individual patients. Of the nine children treated before 1980, three died shortly after onset, two never recovered function after the initial illness, one had a relapsing course and died later, and one had residual nephropathy. Plasma exchange was introduced for the management of non-diarrhea-associated hemolytic-uremic syndrome in 1980; since then, all of the 11 patients have recovered function after the initial episode, but 10 of them had relapses. It appears that with the introduction of plasma exchange there has been an improved outcome in the initial phase, but the survivors tend to have relapses. Atypical (non-diarrhea-associated) hemolytic-uremic syndrome is a heterogeneous yet distinct subgroup of hemolytic-uremic syndrome that differs from diarrhea-associated hemolytic-uremic syndrome on epidemiologic, clinical, laboratory, histologic, and prognostic grounds.

Blood Transfusion↗