Biomedical subjects
Publications and source records attributed to M J Dillon.
Seven cases of cystic fibrosis complicated by chronic salt depletion and failure to thrive were studied. After replacement of the salt deficit, the metabolic abnormalities resolved, and weight gain was rapid. This should be considered as a differential diagnosis in children who have been diagnosed as having cystic fibrosis, but who fail to thrive despite standard treatment.
Aldosterone is important in the regulation of sodium conservation by both kidney and colon. In the very preterm neonate marked urinary salt wasting occurs because of immature renal tubular function, but little is known of the ontogeny of colonic transport processes. Using an in vivo rectal dialysis technique, we have shown that in the human infant the colon has well developed salt conserving mechanisms from early in the last trimester of gestation and that aldosterone is an important regulatory hormone. Sodium transport mechanisms in the colon appear to develop before those in the kidney and it is possible that the colon is the major organ of sodium conservation in the preterm neonate.
We describe two children with multiple abnormalities, neither of whom fits neatly into a classical diagnostic category, but who show overlapping features of Ellis-van Creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia. It seems possible that these three entities form part of a disease spectrum rather than being distinct conditions.
Fetal plasma renin activity (PRA) was measured in 42 pregnancies. Compared to control fetuses, PRA was elevated in three of four hypoxemic fetuses, in two of five with hydrops and in two of five with uropathies. PRA did not change with transfusion in seven alloimmunized fetuses. This study demonstrates PRA in human fetuses and suggests that the renin-angiotensin system can respond to stimuli in fetal life.
The pharmaceutical services provided to the outpatient surgery center of a health maintenance organization (HMO) are described. The satellite pharmacy is managed by the nearby central pharmacy. The satellite pharmacist prepares and dispenses all needed medications and i.v. admixtures, maintains the inventory of all drugs and i.v. supplies, and supplies clinical and drug information. The pharmacist ensures that i.v. admixtures are made according to guidelines, that drug interactions and drug allergies are guarded against, and that each patient has access to oral pain medications and medication counseling while still in the recovery room. The tighter inventory control created by this arrangement helps to reduce costs, and the surgical nursing staff has been relieved of many medication-related activities. The presence of the pharmacist in the surgery center also allows for more accurate documentation of controlled-drug dispensing. The presence of a pharmacist in the surgery center has ensured strict control of drug use and enabled nurses to spend more time on direct patient care.
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The renal function of 12 patients with non vitamin B12 responsive methylmalonic acidaemia has been investigated. Eight patients had reduced glomerular filtration rates, but the plasma creatinine concentration was only raised in those with values of less than 40 ml/min per 1.73 m2 surface area. The reduction in glomerular filtration was a function of the age and the severity of the disease. Plasma urate concentrations were increased in four patients but this may be secondary to the renal disease rather than its cause.
Acute renal failure (ARF) is not listed as a usual form of presentation in hypoxanthine-guanine phosphoribosyltransferase deficiency, despite the gross uric acid overproduction in the defect. We found that a third of such patients may present in ARF when the urinary uric acid/creatinine ratio may be normal, not raised, and the defect may be suspected from the disproportionate increase in plasma uric acid. This is important in view of the potential confusion of uric acid with 2,8-dihydroxyadenine, the even more insoluble purine excreted in the other salvage enzyme disorder, adenine phosphoribosyltransferase deficiency. In that disorder, presentation in ARF is well recognized, the uric acid/creatinine ratio is also normal, but plasma urate is not raised. Our combined experience in these two disorders underlines the importance of early recognition and treatment with carefully adjusted doses of allopurinol, which may reverse or postpone renal failure.
Review of data from 79 children with the haemolytic uraemic syndrome (HUS) showed that the polymorphonuclear leucocyte (PMN) count at presentation in childhood HUS predicts outcome. Logistic regression analysis of several features at presentation identified only the PMN count and the presence of a diarrhoeal prodrome as having a significant effect on the outcome (P less than 0.01 and P less than 0.001 respectively). The geometric mean PMN count was significantly raised in 70 children who had typical HUS following a diarrhoeal prodrome (D+ cases) compared with that of 9 children who had atypical disease without diarrhoea (D- cases) (t-test on log-transformed data, P less than 0.005). Fifty-seven children with D+ HUS who recovered completely had a significantly lower geometric mean PMN count than D+ cases with a bad outcome (P less than 0.001). Four of these patients, who died in the acute stage of the disease, had a significantly higher mean count than the rest of the D+ patients (P less than 0.001). Multiple regression analysis demonstrated that the PMN count in D+ cases was not significantly influenced by haemoglobin concentration, platelet count, length of the prodrome, or the administration of antibiotics in the prodromal period. A high PMN count at presentation in D+ HUS indicates a poor prognosis. The data emphasise the heterogeneity of HUS and suggest that PMN participate in the pathogenesis of the disorder in typical D+ cases but not in atypical D- cases.
The clinical features of 55 cases of autosomal recessive polycystic kidney disease (ARPCKD) have been reviewed. Each had evidence of ARPCKD. The outcomes of 87% were known; 24 had died. Twenty-four of 31 were seen between 1980 and 1986; 7 could not be traced. Forty-five percent presented under 1 month; 38% between 1 month and 1 year; and 9 cases over 1 year. Hyponatraemia occurred in 15 out of 19 aged less than 3 months; hypertension occurred in 65%; splenomegaly in 47% of those surviving more than 3 months. Portocaval shunts were done in 5 aged 2-12 years. Thirteen died of renal failure, 6 under 1 year, and 7 between 1 year and 13 years. Life-table survival rates calculated from birth revealed that 86% were alive at 3 months, 79% at 1 year, 51% at 10 years, and 46% at 15 years. Calculations based on patients who survived to 1 year of age showed that 82% were alive at 10 years and 79% at 15 years. These results reveal an improved prognosis for a condition once assumed to be fatal.
An 8-month-old infant presented with a 1 month history of protracted diarrhea, vomiting, and weight loss. Small intestinal biopsy showed a flat mucosa and there was no clinical improvement with gluten, cow's milk protein, and disaccharidase-free diet. Serial testing for autoantibodies revealed persistent autoantibodies to gut epithelial cells and to renal brush borders; on two occasions, atypical liver-kidney microsomal antibodies were detected. Treatment with steroids produced clinical improvement but the patient finally succumbed with a combination of gut and renal dysfunction. The widespread nature of the antibodies, with clinical involvement of gut, liver, and kidney, suggest an underlying autoimmune mechanism for the pathogenesis of the condition. Serial autoantibody measurements may provide a means to monitor the disease progress and may be a guide to treatment.
The following measurements were made in normal children, children with primary hypertension, and children with secondary hypertension: erythrocyte intracellular sodium concentration, total sodium efflux rate constant, and maximum binding of ouabain to erythrocytes reflecting the number of sodium/potassium adenosine triphosphatase pump sites. Children with primary hypertension had a significantly higher mean erythrocyte intracellular sodium concentration (8.2 compared with 6.6 and 6.7 mmol/l cells), and significantly lower total sodium efflux rate constant (0.5071 compared with 0.6983 and 0.6197) and maximum binding of ouabain to erythrocytes (9.1 compared with 11.7 and 11.0 nmol/l cells) than normal children and children with secondary hypertension, respectively.
Twenty three children aged from 5 to 16 with mild to moderate hypertension were investigated using the orally active angiotensin converting enzyme inhibitor captopril. Falls in both systolic and diastolic blood pressure after a single dose of captopril were significantly correlated with initial plasma renin activity. In addition, some information about the aetiology of hypertension was deduced from the renin response to captopril. The blood pressure response to captopril is a useful screening test for renin dependent hypertension in childhood.
Autoantibodies against components of neutrophil cytoplasm develop during adult vasculitic diseases such as Wegener's granulomatosis and microscopic polyarteritis, and they are predominantly of the IgG class. Similar but distinct antibodies have been described in children with Kawasaki disease and both IgM and IgG class antibodies are represented. This adds another clinically distinct childhood form of vasculitis to the adult forms in which autoantibodies to neutrophil cytoplasmic antigens have been detected.
Two male siblings presented in infancy with hyponatraemia. Levels of plasma renin activity and aldosterone were elevated. Sodium supplementation was necessary to maintain normal sodium balance. Urinary sodium concentration and renal epithelial exchange between sodium and potassium were normal; however, salivary sodium concentrations were markedly elevated with sweat sodium levels being in the upper normal range. Excess salivary sodium loss accounted for sodium depletion in these cases who present a new variant of pseudohypoaldosteronism associated with normal renal sodium transport.
After a rectal biopsy, a 3-week-old boy developed centripetally progressive distal limb gangrene. This was accompanied by transient hypertension and high levels of circulating immune complexes. The ischemia was reversed by prostacyclin infusion, oral corticosteroids and multiple exchange transfusions.
Systemic necrotizing vasculitis in children is a rare but serious disorder. During the past 25 years, 121 children within this disease category have been referred to the Hospital for Sick Children, London (HSC). Classification is difficult but the largest subgroups identified were polyarteritis nodosa (PAN)--29 children and Kawasaki syndrome (KD)--42 children. In spite of modern therapy including steroids, cyclophosphamide, anti-platelet medication, plasma exchange, prostacyclin, high dose gamma globulin and cyclosporin, mortality remains high. Overall mortality for HSC patients was 12% (66% for pulmonary vasculitis, 21% for PAN, and 2% for KD). Recent advances are beginning to shed some light on the etiology and pathogenetic mechanisms involved in PAN and KD. There is now good evidence to support roles for platelet immune complex interactions, anti-neutrophil cytoplasmic antibodies, and anti-endothelial cell antibodies in the pathogenesis. It seems likely that, in KD at least, retroviruses may have an etiological role either by directly infecting endothelial cells or indirectly via T-cells, antibody, or immune complex formation.