CHANGES IN SERUM INSULIN CONCENTRATION DURING PUBERTY AND THEIR RELATIONSHIP TO GROWTH HORMONE

In 40 tall and short children we have demonstrated using oral glucose tolerance tests that there is an increase in serum insulin concentration during puberty with no change in blood glucose concentration. Fasting serum insulin concentration rose from a pre-pubertal value between 4.0 and 5.7 mU/l to values between 11.0 and 14.6 mU/l during puberty. This rise in both fasting serum insulin concentration and the incremental area under the insulin curve is probably due to changes in circulating GH concentrations. In 16 tall girls a rise in serum GH concentration was observed during pubertal growth and the rise was accompanied by a two- to three-fold increase in fasting serum insulin concentration. In 13 children in whom 24 h growth hormone profiles were recorded higher insulin concentrations were seen in those who secreted the most growth hormone. These data suggest that during pubertal growth in diabetic children the standard dosage of insulin administered (0.9 units/kg per day) should be doubled or possibly tripled to maintain good metabolic control and maximize pubertal growth.     

Chronic Amiodarone Reduces Transmural Dispersion of Repolarization in the Canine Heart

Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. In addition to its β-blocking properties, amiodarone is known lo block the sodium, potassium, and calcium channels in the heart. Its complex electropharmacology notwithstanding, the reasons for the high efficacy of the drug remain unclear. Also not well understood is the basis for the low incidence of proarrhythmia seen with amiodarone relative to other agents with Class III actions. The present study was designed to examine the effects of chronic amiodarone in epicardial, endocardial, and M cells of the canine left ventricle. Methods and Results: We used standard microelectrode techniques to record transmembrane activity from endocardial, epicardial, mid-myocardial, and transmural strips isolated from the canine left ventricle. Tissues were obtained from mongrel dogs receiving amiodarone orally (30 to 40 mg/kg per day) for 30 to 45 days or from untreated controls. Chronic amiodarone produced a greater prolongation of action potential duration in epicardium and endwardium, but less of an increase, or even a decrease at slow rates, in the M region, thereby reducing transmural dispersion of repolarization. In addition, chronic amiodarone therapy suppressed the ability of the I_kr, blocker, d-sotalol, to induce a marked dispersion of repolarization or early afterdepolarization activity. Conclusion: Our data demonstrate for the first time a direct effect of chronic amiodarone treatment to differentially alter the cellular electrophysiology of ventricular myocardium so as to produce an important decrease in transmural dispersion of repolarization, especially under conditions in which dispersion is exaggerated. These results may contribute to our understanding of the effectiveness of amiodarone in the treatment of life-threatening arrhythmias as well as to our understanding of the low incidence of proarrhythmia attending therapy with chronic amiodarone in comparison with other Class III agents.     

Limitations and Potentialities of Doppler Echocardiography in the Evaluation of Mitral Flow

Doppler ultrasound has improved the evaluation of mitral valve diseases. There are, however, some limitations to its use. We describe a case of mitral valve disease in which an unusual concomitant rhythm disturbance highlights the limitations of the Doppler-derived pressure half-time method in evaluating the valve area, and the different behavior of the diastolic regurgitation across the two atrioventricular valves.     

Internal Cardioversion of Chronic Atrial Fibrillation in Patients

Transvenous internal cardioversion of chronic AF using a right atrium (RA) coronary sinus (CS) vector requires more energy than cardioversion of paroxysmal AF. Chronic AF is not terminated in 25% of patients using biphasic shocks up to 10 J. We therefore evaluated efficacy, safety, and tolerability of internal cardioversion using a "unipolar' configuration (RA to skin patch) and biphasic shocks in patients with long-lasting AF and different heart disease. In each patient, biphasic R have synchronous shocks were delivered between a large defibrillating surface area electrode in the RA and a skin patch in the left prepectoral position. Defibrillation protocol started with a test shock of 0.4 J. Shocks were repeated and increased until termination of AF or a maximum of 34 J. Sedation was used when the patient described the shock as painful. This study included 11 patients with a mean age of 67 ± 8 years (range 56–83). AF duration was ± 1 month in all patients with a mean duration of 11 ± 11 months (range 2–36). Underlying heart disease was present in all patients and the mean left atrial dimension was 43 ± 9 mm (range 26–57). AF was terminated in 10 of 11 patients (91 %) with a mean delivered energy of the successful shocks of 18.7 ± 8.7 J (median energy 16.9 J; range 7.3–32.5) and a mean leading edge voltage of 564 ± 129 V. The mean shock impedance at the defibrillation threshold was 71 ± 13 Ω, (range 59–103). A total of 131 shocks were delivered without any complication and proarrhythmia episodes. We conclude that low energy "unipolar" internal cardioversion is a simple, safe, and effective technique for termination of chronic AF in patients with heart disease. The procedure is often tolerated under light sedation.     

HIGH LEVEL OF A NERVE GROWTH FACTOR IN THE SERUM OF A PATIENT WITH MEDULLARY CARCINOMA OF THE THYROID GLAND

The serum of a patient with a familial medullary thyroid carcinoma showed levels of a factor, active in the nerve growth factor (NGF) bioassay and cross-reacting immunologically with mouse NGF, 20-1000 times higher than sera from normal controls or from patients with unrelated tumours. Variations of the level of this factor in the serum closely correlated with the progression of the disease. One of the patient's sons, apparently clinically normal, also showed high levels of this factor in the serum, raising the possibility that abnormality in the production of this factor could be present at an early stage of the disease.     

Cyclols,cyclodepsipeptides, and N-acyl-diketopiperazines from linear precursors: Synthesis and crystal structure of 10-membered cyclodepsipeptides

In order to investigate the relative formation tendency of different tautomeric ring systems (cyclols, cyclodepsipeptides and corresponding N -acyl-diketopiperazines), two linear peptide precursors containing proline as C -terminal residue, have been synthesized and subjected to cyclizing conditions. Boc-Ser-Phe-Pro-ONp (I) gave three isomeric cyclic compounds: Boc-Ser-Phe-Pro-(IV), N -(Boc-Ser)-cyclo -(Phe-d -Pro) (III) and the corresponding aza-cyclol (II). Starting from Hyb-Phe-Pro-ONp (V) two epimeric N (3-hydroxybutyryl)diketopiperazines (VI) and (VII) and the corresponding 10-membered cyclodepsipeptide (VIII) could be isolated. Crystal and molecular structure of VIII is reported. Crystals of VIII are orthorhombic, P2₁2₁2₁ with a = 9.684, b = 22.985, c = 7.841, z = 4. The two peptidic bonds are cis with ω values of 6.6° and — 18.1°, whereas the lactonic bond is of transoid type. The pyrrolidine ring has C₂—Cγ-exo conformation.     

A novel algorithm for the coupling control in solid-phase peptide synthesis

This paper describes a new method for the evaluation of conductimetric data collected during the in-line monitoring of the coupling step in solid-phase peptide synthesis. The control scheme relies on a feed-forward artificial neural network algorithm which can predict the final yield of the reaction within its initial 5 min by analyzing the conductivity signal profile. The yield values predicted by the artificial neural network algorithm result in good accordance with the data obtained by the commonly used ninhydrin test. © Munksgaard 1997.     

SPPS of difficult sequences

The H-Ala-Arg-(Ala)₆-Lys-OH sequence is a biologically interesting ‘difficult sequence’ presenting N^α-Fmoc deprotection and coupling problems. Different chemical conditions and synthetic strategies have been tested in order to overcome the problems due to sequence-dependent interactions. In particular, it was confirmed that different solvents in the deprotection step did not provide any significant improvement, but the use of a more efficient base in the deprotection mixture avoided insufficient unblocking of N^α-protecting group; problems due to partial coupling in the last steps of the synthesis were solved by double coupling techniques. Moreover, the synthesis of the model peptide was carried out using both ‘continuous flow’ and ‘batch’ techniques. The present results demontrate that on-line monitoring of the deprotection step by absorbance measurements represents a very effective tool to detect the onset of internal aggregations during the synthesis. © Munksgaard 1997.