Effects of single and repeated clonidine administration on the properties of central and peripheral alpha 2-adrenoceptors in man.

The centrally acting alpha 2-adrenoceptor agonist clonidine was used to assess the sensitivity of alpha 2-adrenergic neurotransmission in man, using receptor-binding studies and clonidine-induced growth hormone response. Neither acute (2 micrograms/kg body weight) nor subchronic (3 days, 2 x 150 micrograms/kg body weight) administration of clonidine affected platelet alpha 2-adrenoceptor number in humans as judged by 3H-yohimbine and 3H-UK-14,304 binding. The same treatment also did not modify central postsynaptic alpha 2-adrenoceptor function in the same individuals as assessed by clonidine-induced growth hormone responses. Similarly, subchronic (3 days, 500 micrograms/kg body weight, i.p.) or chronic (14 days, 500 micrograms/kg, i.p.) administration of clonidine to mice failed to change 3H-yohimbine or 3H-UK-14,304 binding sites in membranes prepared from frontal cortex. On the other hand, in vitro experiments using mouse frontal cortex or human platelet membranes showed pronounced reduction of 3H-UK-14,304 but not of 3H-yohimbine binding sites after incubation with several adrenoceptor agonists. The data indicate that acute and subchronic clonidine treatment may not change alpha 2-adrenoceptor sensitivity in humans or mice as assessed both at the functional and receptor level.

The cholinergic REM induction test with RS 86 after scopolamine pretreatment in healthy subjects.

A shortened latency of rapid eye movement (REM) sleep is one of the most stable biological abnormalities described in depressive patients. According to the reciprocal interaction model of non-REM and REM sleep regulation, REM sleep disinhibition at the beginning of the night in depression is a consequence of heightened central nervous system cholinergic transmitter activity in relation to aminergic transmitter activity. A recent study has indicated that muscarinic supersensitivity, rather than quantitatively enhanced cholinergic activity, may be the primary cause of REM sleep abnormalities in depression. The present study tested this hypothesis by treating healthy volunteers for 3 days with a cholinergic antagonist (scopolamine) in the morning, in an effort to induce muscarinic receptor supersensitivity. On the last day of scopolamine administration, RS 86, an orally active cholinergic agonist, was administered before bedtime to test whether this procedure would induce sleep onset REM periods. Whereas scopolamine treatment tended to advance REM sleep and to heighten REM density in healthy controls in comparison to NaCl administration, the additional cholinergic stimulation did not provoke further REM sleep disinhibition. This result underlines the need to take a hypofunction of aminergic transmitter systems into account in attempts to explain the pronounced advance of REM sleep typically seen in depressives.

[Radiographic examination of the colon in Denmark. A questionnaire study]. / Røntgenundersøgelse af colon i Danmark. En enqueteundersøgelse.

Technical and practical routines for barium enema X-ray examinations in Denmark were investigated using of questionnaire to all hospitals and clinics. Most departments use a routine double contrast technique. In spite of the limited size of the country there are great variations in preparation and technique. Only a few departments used laxatives and increased fluid intake for one to three days. All departments send written instructions to out-patients but only a few have written instructions for in-patients. The time interval from referral to examination is short for in-patients but varies for out-patients.

A simple but highly sensitive radioreceptor assay for the determination of scopolamine and biperiden in human plasma.

Simple and sensitive methods are described for the determination of scopolamine and biperiden in human plasma. Each method consists of two steps. After extraction of scopolamine and biperiden with chloroform or n-hexane respectively and evaporation of the organic solvent, both drugs are determined by their ability to inhibit the specific binding of tritiated N-methyl-scopolamine to mouse brain homogenates. The lower limits of detection are plasma levels of about 50 pg/ml scopolamine and about 200 pg/ml biperiden.

The dexamethasone suppression test and suicide attempts.

We examined covariations between results of the dexamethasone suppression test (DST) and suicidal behaviour for 44 patients who had attempted suicide at least once; the suicide methods, diagnoses and time factors were controlled for. The control groups comprised 82 psychiatric patients and a sample of 69 patients with endogenous depression. In spite of hypotheses suggesting the contrary, there was no significant relationship between DST results and acute suicide attempts. Although patients who had used "soft" methods were often suppressors, chi-square tests using the suicide classification of the ICD-9 as well as tests employing more precise subcategories failed to reveal any significant covariation. In groups of patients with an identical diagnosis of endogenous depression, the sensitivity of the DST with regard to suicide attempts was 52%. The difference between suppressors and nonsuppressors in previous suicide attempts was insignificant. Further, the Hamilton Rating Scale for Depression profiles of DST suppressors and nonsuppressors showed no significant differences with regard to either different symptoms or the evaluation of acute suicide risk.

[Studies of the reliability and validity of the German version of the Montgomery-Asberg Depression Rating Scale (MADRS)]. / Untersuchungen zur Reliabilität und Validität einer deutschen Version der Montgomery-Asberg Depression-Rating Scale (MADRS).

In both its original and German version, the Montgomery-Asberg Depression-Rating Scale (MADRS) has proved to be efficient and practical, and the level of its interrater reliability would appear to be satisfactorily high. With regard to the detection of changes occurring during the course of a depressive phase, this scale exhibits a degree of sensitivity that is comparable to that reported for the HAMD. The concurrent validity between the MADRS and the HAMD is higher over time (.94) than in cross-section (.85). Factor analyses have demonstrated that the MADRS is capable of recording more psychological symptoms of depression than the HAMD. Thus, the MADRS should be applied in combination with other rating scales. Contrary to the intentions of the devisers of this scale, it has been found that, significantly different assessments may result when the same patient is rated by various groups (psychiatrists, psychologists, students and psychiatric nurses). These differences are of practical relevance and are greatest for the first assessment. Clearly, the selection of the time of rating as well as the length of the time period to be included in the evaluation are of particular importance. Even though it has been emphasized that the operationalization of the MADRS is very good, it would appear that also special training in the use of this rating scale is necessary.

Radiologic findings and weight loss following gastroplasty for morbid obesity.

Gastroplasty aimed at treatment of morbid obesity creates a small proximal pouch and a narrow stoma to the remainder of the stomach. In 11 consecutive obese patients subjected to gastroplasty radiologic examinations of the stomach were performed before operation and one week, 3 and 12 months postoperatively. All stomachs were normal before operation. A significant decrease in pouch area and increase in stoma diameter were registered over the observation period. There were no statistically significant correlations between postoperative weight loss and stoma diameter or pouch area. Nor was retention in the pouch one week after gastroplasty related to weight loss. Radiographic evidence of gastroesophageal reflux was present in only one patient. The described method of follow-up is evidently not suited to predict the outcome of gastroplasty.

Clinical investigations into antidepressive mechanisms. II. Dexamethasone suppression test predicts response to nomifensine or amitriptyline.

This prospective study investigates the possibility of a central noradrenergic-cholinergic imbalance in subgroups of depressed inpatients using the dexamethasone suppression test (DST) as one peripheral indicator. The DST was performed in 43 depressed inpatients. Subsequently, a group (n = 20) of DST suppressors (DST-) and a group (n = 23) of DST nonsuppressors (DST+) were treated under double blind conditions with either nomifensine (NOM) a noradrenaline potentiating drug, or amitriptyline (AMI) a noradrenaline potentiating and strong anticholinergic compound. DST+ depressives responded favorably to AMI, but not to NOM. Conversely, DST- depressives responded favorably to NOM but less well to AMI. Together with other biochemical findings this data suggests: 1) a hypofunction of the noradrenergic system in DST- patients who may, from a clinical point of view, usually show minor or 'neurotic' depressions; 2) a hypofunction of the noradrenergic and a hyperfunction of the cholinergic system in DST+ patients who may present a more severe or 'endogenous' depression. These data suggest a biochemical heterogeneity of depression and offer an aid for a more specific antidepressive drug therapy.

Minute rhythm of electrical spike bursts of the small intestine in different species.

Electrical activity of propagating spike bursts recurring at minute intervals was recorded from the small intestine by chronically implanted electrodes in the rabbit, cat, dog, sheep, and pig. This "minute rhythm" has been recorded previously from the intact human small intestine. It occurs in the jejunum with a period duration of 0.5-2.0 min in all species examined. The minute rhythm was accompanied by pressure waves propagating over a short distance, and the activity was most prominent before the onset of phase III of the myoelectric complex. The minute rhythm was activated by the infusion of saline in the jejunum, and it may possibly reflect a normal mechanism for the transport of fluid content.

Congenital cholesteatoma. Preservation of cochlear function after extensive labyrinthine destruction.

A patient with a large congenital cholesteatoma of the left temporal bone is presented. The case is unique in that, although the cholestetoma invaded all three semicircular as well as the basal coil of the cochlea, the patient retained normal hearing. She had an almost complete left-sided facial paralysis, yet she retained sensori-neural hearing postoperatively, in spite of removal of the superior part of the labyrinth (semicircular canals and utricle). The possible mechanisms behind such an unusual event are discussed together with the possible function of the utriculo-endolymphatic valve.

Urinary kallikrein in normotensive subjects and in patients with essential hypertension.

Basal 24 hour urinary kallikrein excretion of 20 patients with uncomplicated essential hypertension did not differ significantly from that of 18 normotensive age-matched control subjects. 4 of the 20 hypertensive patients, however, had low kallikrein excretion. Furosemide (40 mg i.v.) caused an increase of urinary kallikrein excretion in the normotensive subjects and in most of the patients with essential hypertension. The stimulating effect of furosemide was less pronounced or even absent in 7 hypertensives. No circadian rhythm of urinary kallikrein excretion was observed. There were weak correlations between 24 hour kallikrein excretion and urinary volume (r=0.59; p < 0.05), and potassium excretion (r=0.51; p < 0.05) in the normotensives. In the hypertensives correlations were found between 24 hour kallikrein excretion and potassium excretion (r=0.51; p < 0.05), aldosterone excretion (r=0.57; p < 0.01), and creatinine clearance (r=0.59; p < 0.01). Our findings do not support the concept that the renal kallikrein-kinin system might play a primary role in the pathogenesis of essential hypertension.

Urinary kallikrein in normotensive subjects and in patients with essential hypertension.

1. Excretion of urinary kallikrein was normal in 13 out of 15 patients with uncomplicated essential hypertension. 2. Frusemide increased urinary kallikrein excretion in normotensive subjects and in patients with essential hypertension. The stimulating effect of frusemide on urinary kallikrein was significantly diminished in patients with essential hypertension. 3. No correlations of urinary kallikrein with sodium, potassium, and aldosterone excretion were found. 4. The results do not support the idea that urinary kallikrein plays a primary role in the pathogenesis of essential hypertension.

Migrating electrical spike activity in the fasting human small intestine.

The purpose of the present investigation was to describe characteristics of migrating electrical phenomena in the human small intestine. A specially designed probe with several bipolar electrodes was placed in the upper small intestine of 5 normal, fasting volunteers for continuous registration of electrical spike potentials. A migrating myoelectric complex was observed resembling observations made previously in animal experiments. The active phase consisted of regular spike potentials propagating distally at a mean velocity of 12 cm/min, and a duration of about 5 min. In addition a "peristaltic rush" was observed consisting of spike potentials with a high amplitude, propagating distally at a mean velocity of 2 cm/sec and a duration of about 5 sec.