Exogenous interleukin-2 can rescue in-vitro T cell activation and proliferation in patients with a novel capping protein regulator and myosin 1 linker 2 mutation.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; aged 2·5-10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-base pairs deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with the addition of IL-2 in different concentrations. CD25 and interferon (IFN)-γ levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8+ and CD4+ T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8+ T cells from all patients demonstrated significantly reduced IFN-γ production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFN-γ production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.

Allergic enterocolitis presenting as recurrent necrotizing enterocolitis in preterm neonates.

An uncommon clinical entity mimicking necrotizing enterocolitis (NEC) is allergic enterocolitis secondary to cow's milk protein allergy. Although milk protein allergy is the most common food allergy among infants and young children, the incidence and prevalence of this disease entity presenting as enterocolitis in neonates is not well documented. We report this case of milk protein-associated allergic enterocolitis to highlight the unusual recurrent presentation as NEC, (with recurrent pneumatosis, bloody stools) managed successfully with modification of milk formula.

Measuring interface pressures in mattresses.

This evaluation compared the pressure support qualities of three mattresses by measuring the interface pressures using 20 subjects. The results indicate that the Pegasus Airwave mattress had significantly higher readings than Quattro DC2000 (p = 0.021, 95% confidence level) and the Nimbus II (p = 0.009, 99% confidence level) but that there is no significant difference between interface pressures for the Quattro DC2000 and the Nimbus II.

Evaluating pressure-relieving mattresses.

In this study, three mattresses were evaluated to assess their effectiveness in relation to the pain and discomfort experienced by 40 patients with neurological disorders who had Waterlow scores > or = 15 and required pressure support. The results indicate that one mattress (the Quattro DC2000) performed significantly better than the other two (Nimbus II and Pegasus Airwave).

Letters.

ALTERNATING-PRESSURE MATTRESS REPLACEMENTS.

Recurrent ventricular tachycardia responsive to verapamil.

We describe five young patients with recurrent ventricular tachycardia in the absence of organic heart disease. In all patients tachycardia could be terminated or prevented with verapamil. Tachycardia in four patients was very similar, with a QRS pattern of right bundle branch block and left axis deviation. Electrophysiology studies in two patients showed that VT was inducible in one patient (rapid atrial or ventricular pacing, ventricular extrastimuli) but not in the other. The clinical and electrocardiographic similarities in these patients suggest that their ventricular tachycardias may share a common pathophysiology and may be dependent on slow channel activity.

Steady-state serum quinidine concentration: role in prophylactic therapy following acute myocardial infarction.

Steady-state serum quinidine concentrations were monitored in 24 patients with acute myocardial infarction who were on a 1,300-mg daily dosing regimen. Mean serum concentrations spanned the therapeutic range, from 2 to 6 microgram/ml in 21 patients. In no patient was the level of 7 microgram/ml exceeded. Mean levels were similar in patients with congestive heart failure [3.6 +/- 1.5 (SD) microgram/ml] as in those free of failure (3.2 +/- 1.3 microgram/ml), and did not vary with impairment of renal function. There was a significant correlation between mean individual serum quinidine concentrations and the rate-normalized QT interval prolongation (r = 0.54, P less than 0.01); however, variability of the response was high. Variability of the mean serum quinidine levels among individuals was 41%. Variability within individual patients was only 18%. In the individual patient receiving prophylactic oral quinidine therapy, monitoring serum quinidine levels appears to be an accurate, reproducible and pharmacologically significant guideline to therapy.

Value of serum digoxin concentration measurement in the control of digoxin therapy in atrial fibrillation.

The association between steady-state serum digoxin concentrations and control of ventricular response rate (VRR) was studied in 53 consecutive patients with atrial fibrillation. Decreases in VRR were significantly correlated with serum digoxin (rs = -0.22, P less than 0.05). Clinical responses were appropriate to serum digoxin concentrations in 37 patients (69.8%) and were inappropriate in 16 (30.2%) (P less than 0.05). Complicating clinical factors were present in all eight patients with inappropriate responses to therapeutic serum digoxin (0.5 to 2.0 ng/ml) (P = 0.046), but were also found in many patients with appropriate responses and thus could not serve to differentiate between the two categories. Digitalis intoxication occurred in one of the three patients with a concentration of serum digoxin greater than 2 ng/ml (P = 0.056). In 30% of our patients with atrial fibrillation, monitoring of serum digoxin was of value in identifying inappropriate therapeutic responses indistinguishable by clinical means and in defining the subgroup of refractory cases, which allows the prevention of digitalis intoxication.

Steady state serum concentrations and renal clearance of digoxin in neonates, infants and children.

Steady state serum concentrations of digoxin were determined repeatedly in 34 infants with congenital heart disease. Simultaneous measurements of renal clearances of digoxin, creatinine and urea were obtained in 29 of the subjects. Serum digoxin concentrations were markedly higher in children under the age of 3 months than in those over this age, despite equal weight--adjusted 24 h doses. This finding was explained by a very rapid increase in renal digoxin clearance in the first 3 months--32 +/- 7 ml/min/1.73m2 at 1 week to 65.6 +/- 30 at 3 months. The subsequent increase in digoxin clearance was much slower, e. g. to 87.7 +/- 43 ml/min/1.73m2 at 12 months. Renal clearance of digoxin was equally well correlated with creatinine clearance (r = 0.87) as with urea clearance (r = 0.83), but it exceeded that of creatinine in all age groups. The findings indicate that both glomerular and tubular function is involved in the renal elimination of digoxin in young children, and that development of renal elimination of the drug parallels that of the maturation of renal function in the early months of life. The neonate and infant with congestive heart failure display impaired ability to eliminate digoxin. The impairment lessens rapidly with the development of renal function over the first 3 months of life. Diminished doses of digoxin should be advocated in this age group if therapeutic serum concentrations of the drug are to be maintained and toxicity avoided.

Steady state serum digoxin concentration in relation to digitalis toxicity in neonates and infants.

Steady state serum digoxin concentrations were determined in 34 neonates and infants receiving standard maintenance doses of the drug. Digitalis intoxication, diagnosed by ECG criteria, occurred in four of 13 patients with a serum concentration above 2 ng/ml and not in any of 21 subjects with a serum digoxin concentration below this level. This association was found to be significant. It seems that the concept of increased tolerance to digoxin hitherto ascribed to infants is not tenable and that the monitoring of serum digoxin concentration is essential to treatment in this age group.