The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline,l-deprenyl and pargyline

The kinetics of inhibition of rat liver mitochondrial monoamine oxidase by clorgyline, l-deprenyl and pargyline are consistent with a mechanism whereby a reversible interaction between the inhibitor and the enzyme active site under conditions of thermodynamic equilibrium is followed by a time-dependent formation of the covalently-bound enzyme-inhibitor adduct. The K_i value for the reversible interaction between clorgyline and monoamine oxidase A is about 1000 times lower than that towards the B-form of the enzyme, and this difference is sufficient to account for most, but not all, of the selectivity of the inhibition caused by this compound. The K_i value of the monoamine oxidase B selective inhibitor l-deprenyl towards that form of the enzyme is only about 40-fold lower than that towards the A-form. However, in this case, the rate of formation of the irreversible adduct is considerably faster for the B-form than for the A-form and this makes a major contribution to the selectivity of this compound. Pargyline shows a K_i value towards monoamine oxidase B that is only 8 times lower than that towards the A-form and in this case the rates of formation of the enzyme-inhibitor adducts are similar. The significance of these results are discussed in terms of the selective inhibition of monoamine oxidase.     

Prolactin and cortisol responses to the experience of low back pain

Demographic, clinical and psychological characteristics of 92 patients with low back pain were correlated with prolactin and cortisol levels in cerebrospinal fluid (CSF). Somatization and depression scores correlated statistically significantly with the CSF serum ratio of prolactin both in men and in the total group. An increased CSF/serum ratio of cortisol was slightly associated with somatization scores in the total group. Multiple stepwise regression, furthermore, revealed that somatization, anxiety and one of the pain indices contributed to the variance in the CSF prolactin level, which was mostly dependent on the respective serum level. Sex and electromyographic findings (EMG) accounted for 12 and 7%, respectively, of the variance in the afternoon cortisol levels. Women reported more somatization and depression feelings than did men. Most of the data support our earlier assumption that male and female pain patients have different coping mechanisms. In spite of the common underlying endocrine responses to distress in men and women, gender differences in psychological response appear to modify endocrine responses to the experience of low back pain.     

The experimental production of a persistent ductus arteriosus for testing catheter closure devices

An experimental model was constructed to simulate a persistent ductus arteriosus (PDA) in infants. In 21 beagles (mean weight, 8.2 kg), a piece of subclavian artery was interposed between the main pulmonary artery and the aorta, thereby creating a large left-to-right shunt across the short, straight arterial pathway. There were no intraoperative complications. Three animals died postoperatively of stenosing tracheitis, pneumothorax, or bronchopneumonia. The model proved suitable for the serial testing of a new transvenous catheter closure procedure. Occlusion of the shunt was mandatory within a day after placement or severe heart failure would occur. Twelve animals with a released silicone double-balloon plug inside the vascular connection had a long-term follow-up of up to three years. Autopsy findings after the death of the animals at specified intervals revealed smooth ingrowth of the anastomoses and occlusion, by endothelialized fibrous tissue, of the pulmonary and aortic sides of the plugged experimental PDA within a month.     

Studies of some characteristics of molecular dissolution kinetics from rotating discs

The maximum mass transfer from solid to liquid phase i.e. the intrinsic rate of dissolution has been shown to be experimentally accessible with good precision using a generalized rotating disc method in combination with extrapolation to infinite speed of revolution and/or infinite distance from the disc to the center of rotation. The method has with very good result been applied to the determination of dissolution rates from non-disintegrating discs of sulfamethizole and alaproclate hydrochloride in water. In the present paper assumptions for the theory of such experiments are reviewed and compared with numerical values for a number of characteristic kinetic parameters applying simple mathematical models. This comparison supports the assumptions made. The modified rotating disc method described in this paper could therefore be recommended as part of a preformulation program for new solid drug compounds.     

Iron overload in cardiac valvular disease and pure red cell aplasia: treatment with desferrioxamine

A patient was noted to have mitral stenosis in 1969, which by 1982 had progressed to grade III severity. In 1980 she was found to have pure red cell aplasia which was treated by transfusion. In this report we describe the control of iron overload using desferrioxamine and discuss the role of this drug in the treatment of hemosiderosis.     

Modifications in the psychopathologic definition of schizophrenia—Alterations during the last two decades: Expectations for the future

Since Kraepelin,¹ at the end of the last century, compounded some distinct psychiatric disorders already described by others into a nosological entity that was subsequently named “schizophrenia” by Eugen Bleuler,² discussion on the psychopathological criteria to be employed in diagnosis of this disease has not ceased. The diagnostic guidelines in practice up to the 1960s have, during the last two decades, been subjected to increased questioning, out of which new psychopathological concepts seem to be emerging.     

Hematomyelia during anticoagulant therapy

An unusual case of hematomyelia during anticoagulant therapy is reported in a patient after cardiac surgery. A review of the pertinent literature is presented. After medical and surgical treatment, the transverse symptoms largely subsided with rehabilitation of the patient.