Effect of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--I. Growth hormone.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced growth hormone (GH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). DMI-induced GH stimulation was not significantly different after DMI i.v. alone (n = 12) than after three days' pretreatment with 12 mg methysergide p.o. in another group of subjects (n = 12). Following combined administration of DMI and propranolol (15 mg i.v.), GH secretion was significantly increased by 25 mg DMI (p less than 0.05) and 50 mg DMI (incomplete block design, n = 18). GH secretion was significantly lower (p less than 0.01) after DMI in combination with 60 mg phentolamine i.v. compared to that after administration of DMI alone in the same group (n = 12). Following 10 mg yohimbine i.v. in combination with DMI (n = 6), the DMI-induced GH increase was also significantly less (p less than 0.05) than that after DMI alone. The DMI-induced GH increase following DMI plus 1 mg prazosin p.o. (n = 12) was comparable to that after DMI alone. The results indicate that the GH-stimulating effect of DMI is primarily related to the ability of DMI to inhibit noradrenaline (NA) reuptake. Should serotonergic receptors be involved in the DMI-induced GH secretion at all, they transmit a positive stimulus. The alpha-1 receptors are most likely not (or not essentially) involved, whereas alpha-2 receptors affect the DMI-induced secretion positively, and beta receptors have an inhibitory effect.

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--II. Prolactin.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced prolactin (PRL) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). Following administration of methysergide (12 mg p.o., n = 12), a significantly lower (p less than 0.01) DMI-induced PRL secretion compared to DMI alone in another group of subjects (n = 12) was observed. Combined administration with propranolol (15 mg i.v.) significantly enhanced the DMI-induced PRL secretion compared to DMI 50 mg i.v. alone (n = 18, incomplete block design) (p less than 0.01). Neither combined administration with phentolamine (60 mg i.v., n = 12), yohimbine (10 mg i.v., n = 6), nor prazosin (1 mg p.o., n = 12) significantly influenced the DMI-induced PRL secretion compared to DMI alone in the same subjects. The results of the present study, especially the inhibitory effect on DMI-induced PRL secretion of methysergide, indicate that the primarily noradrenaline (NA) and lesser serotonin (5-HT) reuptake inhibiting antidepressant DMI stimulates PRL secretion via 5-HT neurons. Furthermore, the significantly enhanced PRL release following combined administration of DMI and propranolol suggests that a noradrenergic inhibitory effect also may be involved in the transmission of the PRL stimulus.

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--III. Hypothalamo-pituitary-adrenocortical axis.

In this report the effects of various receptor blockers on the desimipramine (DMI)-induced cortisol (ACTH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker, i.e. methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). In addition, the effect of prazosin on DMI-induced ACTH stimulation was examined. DMI-induced cortisol stimulation was not significantly different after DMI alone (n = 12) from that after three days pretreatment with methysergide (12 mg p.o.) in another group of subjects (n = 12). Neither the combination of DMI plus propranolol (15 mg i.v. n = 18, incomplete block design) nor that of DMI plus phentolamine (60 mg i.v. n = 12) had a significant influence on DMI-induced cortisol secretion. Following combined administration with yohimbine (10 mg i.v.), cortisol secretion was higher compared to that after DMI alone in the same group (n = 6). DMI-induced cortisol secretion was significantly lower (p less than 0.01) following combined administration with prazosin (1 mg p.o. n = 12), as was DMI-induced ACTH secretion (p less than 0.05) in these subjects. The findings of these trials, especially those of the prazosin trial, indicate that DMI-induced stimulation of cortisol and ACTH secretion is attributable to the noradrenaline (NA) reuptake inhibiting effect of DMI, and that the stimulus is transmitted with the aid of noradrenergic alpha-1 receptors. Alpha-2 receptors possibly exert a negative influence on this effect.

Comparison of growth hormone and prolactin stimulation induced by chlorimipramine and desimipramine in man in connection with chlorimipramine metabolism.

In order to compare the effects of chlorimipramine (CI) and desimipramine (DMI) on growth hormone (GH) and on prolactin (PRL) secretion equal doses of 25 mg CI or DMI were administered i.v. to 12 healthy subjects each. In this dose, DMI, which primarily inhibits norepinephrine (NE) uptake, induced a significantly higher GH stimulation, compared to CI, whereas CI, which primarily inhibits serotonin (5-HT) uptake induced a significantly higher PRL stimulation, compared to DMI. Following DMI administration, an increase in GH (greater than 7.5 ng/ml) was found in all subjects, after CI in only about 50% of the subjects. The varying interindividual GH secretions after CI are discussed on the basis of the different plasma levels of CI and of its metabolite desmethyl-chlorimipramine (DCI), which is a NE uptake-inhibitor.

Local experience in the diagnosis of avascular necrosis of the femoral head in adults using magnetic resonance.

We analyzed MRI results from 36 patients referred for testing to assess the degree of advancement of non-traumatic avascular necrosis (AVN) of the femoral head in adults (24 cases) or for diagnosis in difficult cases (12 cases). 32 patients were found to have AVN of the femoral head with various degree of advancement, mostly stages III and IV. In three cases the MRI did not show any pathology within the hip joint, and in one case the MRI picture was consistent with a metastatic lesion. This suggests that the value of the MRI as a sensitive diagnostic tool in the early diagnosis of AVN in adults is underestimated.

DALI-the first human whole-blood low-density lipoprotein and lipoprotein (a) apheresis system in clinical use: procedure and clinical results.

BACKGROUND: The DALI low-density lipoprotein (LDL) apheresis system is the first whole-blood apheresis system in regular clinical use. DALI stands for direct adsorption of lipoproteins, which describes the basic principle of operation of this newly developed LDL apheresis procedure. METHODS: The selective removal of LDLs and lipoprotein (a) [Lp(a)] is performed in human whole blood by adsorption onto polyacrylate-coated polyacrylamide beads in an adsorber. This article describes the results of the first open multicentre clinical trial in 14 patients in whom the safety and the efficacy of the system were tested. All patients were treated on average 17 times on a weekly basis. In total, 238 sessions were carried out during the study without severe side-effects. On average, 7675 mL of the patients' whole blood was processed in about 2 h. Anticoagulation in the extracorporeal system was carried out by first giving a heparin bolus followed by continuous addition of an acid citrate dextrose (ACD-A) infusion during the treatment. RESULTS: The processing of nearly 1.6 times the patient blood volumes resulted in a reduction in the median LDL-cholesterol level by 66-77% (dependent on the system configuration). The Lp(a) concentrations were reduced by 59-73% (dependent on the system configuration). HDL-cholesterol, blood cell count and the other clinical parameters were not significantly affected. CONCLUSION: Based on this short-term evaluation, the DALI apheresis system is a well-tolerated, effective and simple way of reducing LDL and Lp(a) in human whole blood. The system has been introduced to clinical practice. However, to use the DALI apheresis system in clinical routine, further evaluation of long-term effects is required.