Long-Lasting Catch-up Growth under Bio-Methionyl Growth Hormone Treatment in an Infant with Isolated Growth Hormone Deficiency Type 1A1

ABSTRACT. This case report concerns a 7-month-old infant with severe height retardation (–5.0 SD), typical growth hormone (GH)-deficient phenotype, and undetectable GH serum levels in response to three pharmacological stimuli. Diagnosis of isolated GH deficiency type 1A was confirmed by restriction endonuclease analysis of genomic DNA which pointed out GH-N gene deletion. The introduction of bio-methionyl-GH therapy in this patient was followed by a transient and clinically irrelevant appearance of low binding capacity GH antibodies as well as by a long-lasting catch-up growth (42.2 cm) which is continuing 44 months after beginning of treatment. This atypical pattern confirms that immune and growth response to exogenous GH in isolated GH deficiency 1A may be very heterogeneous.     

Different Trends of Changes in Heart Rate Variability in Patients with Anterior and Inferior Acute Myocardial Infarction

Modifications in heart rate variability (HRV) parameters occur after acute myocardial infarction. The aim of this study was to evaluate the trend of HRV change during the acute phase and the first month after myocardial infarction, and establish whether they were affected by the anterior or inferior location of the infarction. The time-domain HRV measures of 59 patients with a first uncomplicated acute myocardial infarction were computed from 24-hour ECG recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and the root mean square successive difference of NN intervals (RMSSD) were lower in the patients with anterior myocardial infarction. Although the parameters were similar in all of the patients at day 28, their behavior over time was different (P = 0.01): the SDNN in the patients with inferior myocardial infarction had decreased to the values found in anterior myocardial infarction patients by day 2 but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had diminished in both groups by day 2, but at day 10, had increased in the patients with anterior, but not in those with inferior myocardial infarction. These findings suggest that (1) in the very early phase of myocardial infarction, HRV is different in the two locations, (2) during the first hours of myocardial infarction patients with inferior location showed a greater vagal activity than patients with anterior location that became lower at day 10, and (3) the recovery of HRV is an early phenomenon in both groups, being already evident by the second week after myocardial infarction.     

Comparative study of the effects of nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) on adenosine-induced bronchoconstriction in asthmatic subjects

The effect of nedocromil sodium (4 mg; 7.8 × 10⁻⁶ m ) on adenosine-induced bronchoconstriction was compared with that of a higher dose of sodium cromoglycate (10 mg; 24.1 × 10⁻⁶ m ). Eleven allergic asthmatic patients (mean age 26.28 ± 12.21 years) were studied. Adenosine (0.03–4.00 mg) was administered as nebulized aerosol. The dose of adenosine producing a 20% change in FEV₁(PD₂₀) was calculated from the individual semi-logarithmic dose-response curves. Patients were studied on 4 separate days. On the first day the adenosine challenge was performed; on subsequent days patients were pretreated (20 min before challenge) with either placebo or test drug (nedocromil sodium 2 × 2 mg or sodium cromoglycate 2 × 5 mg) administered by pressurized aerosol in a randomized, double-blind manner. Statistical analysis was performed by two-way analysis of variance. Neither sodium cromoglycate nor nedocromil sodium showed a significant bronchodilator effect. In patients treated with placebo, inhalation of adenosine produced a dose-related bronchoconstriction with a geometric mean PD₂₀ of 0.42 mg. After drug administration the mean PD₂₀ values were 1.29 mg with sodium cromoglycate and 2.30 mg with nedocromil sodium. Both drugs produced a significant increase in mean PD₂₀ value in comparison with placebo and baseline ( P < 0.01). These results demonstrate that nedocromil sodium (4 mg) is significantly more potent than a larger dose of sodium cromoglycate (10 mg) in inhibiting adenosine-induced bronchoconstriction ( P < 0.05).     

Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients

Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects.