Clinical Trial with Authentic Recombinant Somatropin in Japan

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.16 to 1.08 ± 0.12 mEq/litre (mean SEM) at 4 hours after the first injection (p<0.001). Plasma IGF-1 levels increased from 0.80 ± 0.14 units/ml to 1.72 ± 0.50, 3.22 ± 1.02, 3.17 ± 1.20 and 3.63 ± 0.78 units/ml at 24 hours after each daily injection for 4 days (p<0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 ± 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2–5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4–10.0 cm/year with a mean growth rate of 7.4 ± 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.     

A Case of Periodic Somnolence Whose Sleep was Induced by Glucose

A case of a 29-year-old man who exhibited periodic somnolence for periods ranging from 2 to 10 days from the age of 18 onward and whose 3 family members had similar episodes of somnolence is reported. The main symptoms of this case were somnolence and depressive state. The specific manifestations were paraesthesia in the limbs, alteration of body schema, exceptional liking for sweets previous to somnolence, difference in the amount of serum potassium between the interval stage and somnolence stage, and the inducement of sleep by glucose. Carbamazepine plus phenobarbital with an addition of imipramine were effective in the treatment.     

Mononucleosis-like illness in an infant associated with human herpesvirus 6 infection

Illnesses resembling mononucleosis, hematologically characterized by atypical lymphocytosis in the peripheral blood, are caused by other viral infections as well as by a primary Epstein-Barr virus infection. Human herpesvirus 6, a newly isolated member of the herpesvirus group, can also cause a mononucleosis-like illness. Illness associated with human herpesvirus 6 infection mostly occurs in immunocompetent adults. We observed a 3 month old infant who presented with marked atypical lymphocytosis and liver dysfunction. We examined serum samples to detect viral antibodies related to mononucleosis-like illness. Only the titers of antibody against human herpesvirus 6 were elevated. Primary human herpesvirus 6 infection cannot only cause exanthem subitum or present in an inapparent form but can also cause an illness like mononucleosis, even in an infant.     

Determination of Protein Binding of a Highly Lipophilic Drug,Isocarbacyclin Methyl Ester (TEI-9090), Using a Polydimethylsiloxane-coated Glass Beads Assay

Abstract— An adsorption technique with polydimethylsiloxane-coated glass beads (PDMS-GB) was developed to determine the protein binding of a highly lipophilic and hydrophobic drug. The present assay method is based on the quantitative adsorption of unbound drug to the PDMS-GB. This method of batch separation in a glass assay tube has an advantage of simplicity and rapidity. To evaluate the reliability of PDMS-GB assay, we compared the protein binding of diazepam in serum in-vitro measured by ultrafiltration and PDMS-GB assay. There was no significant difference between the extent of binding measured by each method. Using PDMS-GB assay, we determined the protein binding of the prostaglandin I₂ (PGI₂) analogue isocarbacyclin methyl ester (TEI-9090), whose binding cannot be measured by commonly employed techniques (equilibrium dialysis, ultrafiltration, gel filtration or ultracentrifugation) because of a high degree of adsorption to membranes, resins or tubes. The percentage of TEI-9090 bound in human serum, 4% human serum albumin (HSA, fatty acid-free) and dog serum were ～98, ～87 and ～95%, respectively, and these values were independent of TEI-9090 concentration up to 10 ng mL^?1. The binding of isocarbacyclin (TEI-7165) to serum protein in man, dogs, rabbits and rats, determined by ultrafiltration, was also high (>90%). While the displacement of TEI-9090 and TEI-7165 binding to HSA by aspirin, salicylic acid and indomethacin was not observed, clofibric acid and free fatty acids significantly inhibited the protein binding of both compounds. These results indicate that the binding site of TEI-9090 and TEI-7165 on HSA could be identical with the possible binding site of PGI₂.     

THE EFFECT OF α ADRENERGIC RECEPTOR BLOCKADE ON THE GLUCAGON-INDUCED GROWTH HORMONE RESPONSE

The effect of a a adrenergic blockade (phentolamine) on glucagon-induced growth hormone response was tested in five normal men. There was no significant difference in growth hormone concentrations between the glucagon test and the glucagon-phentolamine test (mean maximum level, 23.4 ± 3.7 ng/ml and 23.1 ± 5.9 ng/ml, respectively). Insulin secretion was significantly higher (P < 0.025) 30 and 60 min after an injection of glucagon in the glucagon-phentolamine test. The results suggest that the stimulation of growth hormone secretion by glucagon is not mediated through an a adrenergic mechanism.     

Dynamic Stabilization for Degenerative Spondylolisthesis and Lumbar Spinal Instability

Lumbar interbody fusion is a widely accepted surgical procedure for patients with lumbar degenerative spondylolisthesis and lumbar spinal instability in the active age group. However, in elderly patients, it is often questionable whether it is truly necessary to construct rigid fixation for a short period of time. In recent years, we have been occasionally performing posterior dynamic stabilization in elderly patients with such lumbar disorders. Posterior dynamic stabilization was performed in 12 patients (6 women, 70.9 ± 5.6 years old at the time of operation) with lumbar degenerative spondylolisthesis in whom % slip was less than 20% or instability associated with lumbar disc herniation between March 2011 and March 2013. Movement occurs through the connector linked to the pedicle screw. In practice, 9 pairs of D connector system where the rod moves in the perpendicular direction alone and 8 pairs of Dynamic connector system where the connector linked to the pedicle screw rotates in the sagittal direction were installed. The observation period was 77–479 days, and the mean recovery rate of lumbar Japanese Orthopedic Association (JOA) score was 65.6 ± 20.8%. There was progression of slippage due to slight loosening in a case with lumbar degenerative spondylolisthesis, but this did not lead to exacerbation of the symptoms. Although follow-up was short, there were no symptomatic adjacent vertebral and disc disorders during this period. Posterior dynamic stabilization may diminish the development of adjacent vertebral or disc disorders due to lumbar interbody fusion, especially in elderly patients, and it may be a useful procedure that facilitates decompression and ensures a certain degree of spinal stabilization.     

Which blood gas caused the brain damage?

In order to analyse the effects of various physiological parameters including blood gas data on the cerebral oxygenation, we developed a model to enable us to estimate PtO₂ (tissue PO₂) from these physiological parameters. This model was applied successfully to a set of blood gas data of a patient who had brain damage after cardiac surgery. Contrary to the original impression, we concluded that a very low PaCO₂ of 13 mmHg towards the end of CPB was the most likely cause of his damage.     

Beneficial effects of the prone position on the incidence of barotrauma in oleic acid-induced lung injury under continuous positive pressure ventilation

Background: Factors that contribute to ventilator-induced barotrauma are not well defined. This study investigates the effects of posture on ventilator-induced barotrauma, as well as arterial oxygenation. Methods: Twelve dogs with oleic acid lung injury, lying in the prone position (n=6) and right lateral position (n=6), were mechanically ventilated with continuous positive pressure ventilation for 24 hours. The incidence of pneumothorax and arterial oxygenation were investigated in each position. Results: All animals lying in the lateral position developed pneumothorax in the nondependent thorax, while only one animal in the prone position developed pneumothorax in the left thorax (P < 0.05). Postmortem examination revealed that in the lateral group, the nondependent lung consisted of large areas of emphysematous regions and neutrophil infiltration regions, while the dependent lung was composed of extensive atelectasis and neutrophil infiltration. Lung ruptures occurred in the non-dependent lung at the regions of either emphysematous change or severe neutrophil infiltration. In the prone group, in contrast, both lungs were inflated fairly homogeneously with only small areas of atelectatic and emphysematous changes. In the dog in whom pneumothorax developed, lung ruptures were limited to the regions of severe neutrophil infiltration in the left lung. No animal in either group had a peak airway pressure more than 20 cmH₂O. The peak airway pressures were 17.5 ±1.3 cmH₂O in the lateral group and 16.6±2.1 cmH₂O in the prone group (P>0.05). Tidal volume was comparable between the lateral group (13±2 ml/kg) and the prone group (12±1 ml/kg) before pneumothorax occurred (P>0.05). Arterial oxygenation was much better in the prone group than in the lateral group during the experiment (P < 0.05). Conclusion: It was concluded that in lung injury dogs, the prone position has beneficial effects on the incidence of ventilator-induced barotrauma and arterial oxygenation when compared with the lateral position. Ventilator-induced barotrauma may occur at lower airway pressure.