Dose-related efficacy and safety of formoterol (Oxis®) Turbuhaler® compared with salmeterol Diskhaler® in children with asthma

To compare the dose‐related bronchodilator efficacy and tolerability of formoterol (Oxis^®) Turbuhaler^® with salmeterol Diskhaler^® and placebo in children with asthma. A single‐dose, randomized, double‐blind, incomplete crossover study of 68 children (7–17 years), with moderate‐to‐severe asthma, 82% receiving inhaled corticosteroids. Patients received four of six treatments [4.5, 9, 18, or 36 μg formoterol (6, 12, 24 or 48 μg metered doses), 50 μg salmeterol (metered dose) or placebo] at 12‐h visits, separated by ≥3 days. Forced expiratory volume in 1 s (FEV₁), pulse, blood pressure, electrocardiogram, adverse events and urine formoterol were assessed. The therapeutic ratio of formoterol vs. salmeterol was estimated from the efficacy and systemic effects results. All active treatments significantly improved FEV₁ compared with placebo. Formoterol 9–36 μg provided dose‐related increases over salmeterol in lung function: average 12‐h FEV₁ (increases of 4.9–8.7%, p < 0.001) and FEV₁ at 12 h post‐dose (7.0–12.2%, p < 0.001). The onset of effect of formoterol was also significantly faster than salmeterol for doses ≥9 μg. Salmeterol 50 μg was estimated to be equieffective to 3.3 μg formoterol for 12‐h average FEV₁ and the estimated equieffective dose for a variety of systemic effects was 7.8–13.5 μg formoterol. All treatments were well tolerated. Formoterol (Oxis) Turbuhaler 4.5–36 μg provided dose‐related improvements in bronchodilator efficacy in children with asthma. Formoterol ≥9 μg provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 μg with no increase in systemic effects.     

Penicillin Treatment of Scarlet Fever1

Summary
From various test series during the years 1946–51 consisting of 6,500 cases of scarlatina it appears that penicillin has an excellent effect in preventing complications. Not only in comparison with normally hospitalized patients, but also with entirely isolated patients, there is a clear difference in favor of treated cases. It is also shown that the peroral therapy given was, in spite of the low dosage, very little inferior to injection from the point of view of complications. The effect in preventing complications applied particularly to the bacterial types. A difference is also apparent, however, in regard to toxic types. The only complication of this kind which proved of any significance during the years of the tests was myocarditis. According to Levander-Lindgren's investigations of the material the frequency of myocarditis also diminished as a result of penicillin treatment. This is of particular importance in patients over 15 years, in whom myocarditis is of a more serious character.     

Altered Na+-K+ ATPase activity in uraemic adolescents

The Na⁺-K⁺ ATPase enzyme plays an essential role in the regulation of cell composition and volume. Enzyme activity itself is regulated by substrate availability and several hormones. In adult uraemic patients red blood cell Na⁺-K⁺ ATPase activity is decreased. However, it is unknown if children with uraemia exhibit the same phenomenon. Therefore, in the present study we examined whether endogenous digoxin-like factors (EDLF) and physicochemical membrane properties play a role in the regulation of erythrocyte Na⁺-K⁺ ATPase activity in uraemic children and adolescents. Healthy age-matched children were used as controls. Enzyme activity was measured in detergent-pretreated red blood cells and erythrocyte ghosts. Na⁺-K⁺ ATPase activity (2204 ± 538nmol Pi ml erythrocyte^?1 h^?1 in detergent pretreated erythrocytes; 204 ± 56 nmol Pi mg protein^?1 h^?1 in ghosts) in adolescents with uraemia was lower compared to controls (3245 ± 362 nmol Pi ml erythrocyte ¹ h^?1; 266 ± 37 nmol Pi mg protein^?1 h^?1, p < 0.001, p < 0.05, respectively). Plasma levels of EDLF were elevated in uraemic patients (0.30 ± 0.05 versus 0.21 ±0.04 ng ml^?1, p < 0.01). Furthermore, the membrane lipid component was decreased in patients with uraemia, while the cholesterol/phospholipid ratio and membrane fluidity were similar in both groups. No correlation was found between the decrease in Na⁺-K⁺ ATPase and the increase in EDLF concentration and altered membrane lipid components. Our results demonstrate, that similar to the findings of adults, the activity of Na⁺-K⁺ ATPase is diminished in uraemic adolescent patients, and that uraemia-associated elevation in EDLF and altered membrane components do not play a role in the down-regulation of Na⁺-K⁺ ATPase. Therefore other factors (presence of other inhibitors and/or reduced number of enzyme molecules) should contribute to the lower activity of the Na⁺-K⁺ pump.     

THE DIAGNOSIS OF TAY-SACHS DISEASE1

Gangliosides and neutral aminoglycolipids were determined in several organs from two subjects with classical Tay-Sachs disease. Ganglioside G_M2 was stored in all organs investigated. Of the extraneural organs, the highest concentration was found in the adrenals, spleen and liver. The rectal muscular layer had a high concentration of gangliosides. Rectal biopsy might be used for studies of the nervous ganglioside pattern. The brain tissue showed a many-fold increase of the activities of p-nitrophenylglycosi-dases. The activity of ganglioside sialidase in the brain was not increased in Tay-Sachs and some other neurometabolic diseases. Subfrac-tionation of the glycohydrolases by ultracen-trifugation showed no hexosaminidase activity in the supernatant fraction of the brain in Tay-Sachs disease compared with about 2/3 of the total activity in normal human brain. A simple agarose electrophoretic method was developed for the separation of the hexosaminidases into two fractions, A and B. Hexosaminidase A was virtually absent in Tay-Sachs disease. The known forms of gangliosidoses and their biochemical characteristics are reviewed and a scheme is given for their classification and diagnosis.     

Survival of Cr51-labelled Red Cells from New-born Infants1

Summary
The survival of Cr⁵¹-labelled placental red cells of 10 full-term and 6 premature infants was studied after transfusion to adult recpients. The mean apparent half-life of the red cells from full-term infants was found to be 22.8 days, and that of red cells from premature infants 15.8 days (cf. 27.5 days for red cells from adults). Results obtained by others using the differential agglutination method have indicated a longer life span than that corresponding to the Cr⁵¹ half-times above mentioned. The most probable explanation of this difference seems to be that Cr⁵¹ is eluted more rapidly from fetal red cells than from red cells of adults. This hypothesis is corroborated by the results of experiments in vitro on intact red cells.     

Interleukin-15 enhances CD4+ CD45RA+ expression on umbilical cord blood mononuclear cells

The reduced incidence of graft‐vs.‐host disease following umbilical cord blood (CB) transplantation may be related to the functional immaturity of newborn T cells expressing mainly the naive CD45RA phenotype. Expansion of CD4⁺ CD45RA⁺ T cells using cytokines may benefit neonates and infants with human immunodeficiency virus (HIV) infection, as a preferential decline in CD4⁺ CD45RA⁺ cells has been noted as HIV disease progresses. The aim of the study was to investigate the effect of interleukin (IL)‐15, a novel cytokine similar to IL‐2 in biological activities, on CD45RA/RO expression and apoptosis in umbilical cord blood (CB) and adult peripheral blood (APB) mononuclear cells (MNCs). Prior to culture, CB MNCs contained a greater number of CD4⁺ CD45RA⁺ cells and fewer CD4⁺ CD45RO⁺ cells than did APB MNCs. When incubated with RPMI‐1640 containing 10% fetal calf serum for 7 days, the percentage of CD45RA⁺ cells within CD4⁺ T cells (%CD45RA⁺/CD4⁺) significantly decreased compared to that of fresh CB MNCs. IL‐15 exerted a dose‐dependent increase of %CD45RA⁺/CD4⁺ and a corresponding decrease of %CD45RO⁺/CD4⁺ in CB MNCs, an effect not observed with APB MNCs treated with IL‐15. The percentages of CD45RA⁺ and CD45RO⁺ expression within CD8⁺ cells, however, were not influenced by IL‐15, in either CB or APB MNCs. A greater number of CB MNCs underwent apoptosis than did APB MNCs after 7 days of culture in RPMI‐1640 containing 10% fetal calf serum. IL‐15 did not inhibit apoptosis but induced proliferation comparable to that achieved in APB MNCs. The ability of IL‐15 to preferentially enhance the proliferation of CD4⁺ CD45RA⁺ cells in CB MNCs suggests a role for immunomodulative therapy in HIV‐infected newborns and infants.     

Overgrowth and Enlarged Heart in Mouse Fetuses with Maternally Inherited ThP and twLub2: An Example of Genomic Imprinting in Animals

ABSTRACT T^hp/+ mouse is known to have differing phenotypes depending on gender of the T^hP parent. In the present study, fetuses with maternally [Group A (until day 18 of pregnancy) and Group C (day 19)] and paternally [Group B] inherited T^hP were examined with particular reference to the developmental abnormalities of hearts. In addition, a small number of fetuses with maternally inherited t^wLub2 on day 19 were compared with T^hp. Group A T^hP fetuses had greater body weight, possibly larger body size, generalized edema (100%), marked enlargement of the hearts (100%) and hypoplastic pulmonary trunk (73.7%). There were no such malformations in Group B T^hP fetuses or in the controls (+/+) for both groups. The bilaterally thickened ventricular wall of fetal hearts in Group A and C T^hP fetuses bulged into ventricular cavity. The pulmonary valve was also thickened. The labeling indices of the ventricular myocardial cells by BrdU were inclined to be higher in Group A T^hP than in the control (+/+) fetuses. Fetuses of t^wLub2 had abnormalities of the cardiovascular system similar to Group C T^hp. The results suggest that cardiac lesions in fetuses with maternally inherited T^hP and t^wLub2 correspond to cardiomyopathy. Overgrowth and enlarged heart indicate the possibility of T^hP as an animal model for Wiedemann-Beckwith syndrome.     

Case report of common variable immunodeficiency with functional T-helper defect and reduced CD4+ LAM−1 T cells

A 10 year-old boy presenting with an empyema and a previous medical history of recurrent and disseminated infections was investigated immunologically. The serum immunoelectrophoresis showed hypogammaglobulinaemia. The in vitro lymphocyte proliferation to T-cell mitogens (PHA and Con A) was diminished and the response to a T-dependent B cell mitogen (PWM) was severely diminished. Phenotypic analysis of his lymphocytes with monoclonal antibodies revealed normal CD3⁺, CD4⁺ and CD8⁺ cells with a normal CD4: CD8 ratio. Double immunofluorescence with Leu 8 antibody revealed a selective deficiency of the CD4⁺ LAM 1⁻ subset. Co-culture experiments between patient's B cells and supernatants from normal T cells showed that the patient's B cells could secrete Ig in vitro. We suggest that the Leu 8 monoclonal antibody may be useful in defining abnormalities in the regulatory subsets of T lymphocytes and that these abnormalities may be relevant in the pathogenesis of common variable immunodeficiency.