Biomedical subjects
Publications and source records attributed to B Pflug.
Rubidium (Rb+) has an antidepressive effect and shortens the circadian period in animals, whereas Li+, another alcalic metal, lengthens it. When we treated a depressive Li+ nonresponder with Rb+, we found an improvement of depression as well as a phase advance of the temperature rhythm in relation to the rest-activity rhythm.
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3 women aged 37, 44 and 53 years were examined in a long term study (4-5 months) with and without lithium carbonate medication. The subjective condition and complaints of the subjects were recorded. The body temperature was measured each night with a rectal probe and the data analysed using TIMESDIA-program. During the lithium medication, deterioration in the subjects well-being, and somatic disturbances can occur. At the same time variations in the circadian course of the body temperature were demonstrated. In addition to the 24-hour period, longer and shorter periods appear. Based on a chronobiological model a possible dissociation of the oscillator controlling body temperature is suggested.
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The antidepressant effect of rolipram, believed to be based on a new mechanism of action, was investigated in an open phase II study in 10 depressive patients, most of whom had been refractory to previous antidepressant therapy. Five patients displayed a good to very good improvement of their depressive condition. Four patients failed to show any substantial improvement, and therapy had to be withdrawn in one case due to deterioration of the condition. In most cases, the antidepressant effect of the trial preparation became noticeable after 2-4 days of treatment only. Basing on the presented cases, the tolerance can be described as excellent compared to other antidepressants. Although, on the whole the trial yielded very encouraging results, only double-blind trials can determine the true antidepressant efficacy of rolipram.
Siberian chipmunks (Eutamias sibiricus) were kept individually in small cages attached to a running wheel. Under continuous illumination of two different light intensities (0.4-0.9 lux and 400-1200 lux) the influence of Rolipram, a putative new antidepressant, on the period length tau was tested. Under both conditions Rolipram caused a lengthening of tau, a decrease of activity time alpha and an increase of rest time delta, resulting in a decrease of the alpha/delta ratio. These effects of Rolipram could be due to a slowing down of the circadian oscillatory system or an influence on the sensitivity towards light.
The effect of lithium carbonate on the circadian system of man was studied. Four out of eight volunteers living without time cues in isolated huts in the arctic showed a lengthening of the periods of the body temperature rhythm, activity rhythm, and sleep/wakefulness rhythm by c. 1 h. Four of the participants did not show a change in the periods between the placebo and lithium ingestion phases. Two subjects who did not receive lithium salt showed internal desynchronization between the temperature rhythm and the sleep/wakefulness rhythm. Extreme isolation in bunkers is not necessary to allow free running of the circadian system in man. The sleep/wakefulness rhythm, which is very easy to record, was a reliable indicator of the circadian system in the internally-synchronized state.
A 38-year old woman with a bipolar affective disorder was examined for 10 days during a serious retarded depression phase and for 10 days during the subsequent symptom -free interval. During depression the MHPG-excretion showed a significantly shorter circadian periodicity of 20.5 hours, whereas the periodicity of body temperature and VMA amounted to 24 hours. During the symptom-free interval the circadian periodicity of all parameters was 24 hours. These results indicated that the depression phase of a bipolar affective disorder in this patient is related to a desynchronization of central NA function with peripheral NA activity and body temperature.
Proceeding from the hypothesis of disturbed circadian rhythms in endogenous depression, we observed the oral temperature of four patients in a long-term study. The results showed the following: 1) Depression is linked to higher mean daily temperatures compared with normal states. In manic states, the mean daily temperature is even higher than in depressive states. Sleep deprivation as effective treatment causes a decrease in mean daily temperature. 2) The daily temperature maximum changes its position in depressive states. This is interpreted as indicating a disturbed circadian system. 3) A period shorter or longer than 24 h cannot be observed in depressive states.
In long term studies on three endogenous depressive female patients, the circadian course of body temperature has been observed during depressive and manic episodes as well as during the intervals. The patients measured their oral temperature regularly, several times a day. The mathematical analysis, carried out with methods of digital signal processing using an interactive computer program system TIMESDIA, showed the following results: A period length of 24 h, independent on the state of mood. During depression and during mania, however, a greater variability of the daily temperature pattern was found, which resulted from changes of the phase relationship of higher harmonics.
Lithium carbonate was administered during a double-blind crossover experiment lasting 8 weeks, involving 11 healthy volunteers. In psychological tests, no deterioration in mood, performance or memory could be shown. Informal diary entries made by the subjects, however, refer to complaints, particularly relating to vegetative functions, more frequently under lithium medication than during the placebo period. In the interpretation of the findings, it is important to take into account the very high motivation of the subjects.
Five groups of two volunteers lived during four weeks under arctic summer conditions (Spitsbergen) isolated in huts, without time information. They received lithium carbonate or placebo. All showed free-run of their circadian temperature and activity/rest rhythms with periods longer than 24 hours. Under lithium carbonate, a period-lengthening effect can be shown. This could help to understand theprophylactic effect of lithium salts in manic-depressive episodes.
Out of 102 patients suffering from endogenous depression, it was possible to ascertain the duration of episodes in the case of 60 patients. Intraindividual comparisons among patients with unipolar depression show that sleep deprivation therapy causes a tendency to shorter depressive episodes. This tendency is related to the time of application of sleep deprivation: the sooner sleep deprivation is applied within an episode, the better the effect. Younger patients react better than older ones.
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Oral calcium tolerance and urinary cyclic AMP testing was used in the evaluation of 61 unselected patients with stones. The oral calcium tolerance test was easy to perform and was useful in defining several distinct metabolic abnormalities contributing to calculous formation. Oral calcium tolerance testing is more precise than twenty-four-hour urinary calcium determination and should provide a means of determining proper medical treatment of urolithiasis. Urinary cyclic AMP was disappointing as a measure of parathormone activity.
Doppler ultrasound was used to determine the viability of ischemic small intestine and to select the optimum point for resection of nonviable bowel. Twenty ischemic segments of small intestine were produced in dogs by ligating the vascular supply. The Doppler ultrasound probe then was used to determine the last point of arterial flow within the bowel wall. The dogs were reexplored after 24 hours. Histological examination of full-thickness biopsies showed the intestine to be normal in all 20 segments at the last audible Doppler signal, and in 19 of the 20 segments at 1 cm distal to the last signal. Progressive degrees of necrosis were observed at 2 and 3 cm distal to the last signal. Twenty-five segments of ischemic intestine were resected in baboons. All resections performed at the last Doppler signal or 1 cm distal to it were normal 1 month later. Of 15 resections performed at 2, 3, and 4 cm distal to the last signal, 10 showed evidence of stricture or anastomotic disruption. Doppler ultrasound is a reliable method for determining the viability of ischemic intestine and for selecting the optimum point for resection of nonviable bowel.
Cardiovascular risk factors in 566 patients with peripheral arterial disease undergoing major vascular operations were analyzed by chi-square analysis. There were 37 postoperative deaths, for a mortality rate of 8.5%. Cardiovascular complications were responsible for 23 deaths (62%). Five risk factors--congestive heart failure, prior myocardial infarction, prior stroke, arrhythmia, and abnormal electrocardiogram--showed significant individual associations with postoperative cardiovascular complications. A multivariate analysis of these five risk factors and angina led to the development of an equation which predicts the probability of a postoperative cardiovascular complication. The number of complications observed corresponded closely to that predicted by the equation. There was a significantly higher incidence of complications in patients predicted to be at high risk than in those at low risk.
Staging of bilateral carotid endarterectomies 1 to 6 weeks apart has been recommended because of presumed excessive morbidity chiefly related to respiratory problems, hypertension, and neurological deficits. Since data regarding the timing of the second procedure are lacking, an analysis of 79 consecutive patients undergoing bilateral endarterectomies staged from 6 days to 34 months apart (median interval, 52 days) was performed. In addition to postoperative neurological deficits, however, transient perioperative mean systolic and diastolic blood pressures (SBP and DBP) were compared after each side and were correlated with the time interval between the two procedures. No significant difference existed between the two sides in terms of preoperative hypertension, administration of steroids prior to clamping, intraoperative clamp time, the use of shunts, and the duration of operation (P greater than 0.05). Seven temporary neurological deficits occurred after operation, six after the first and one after the second endarterectomy. One permanent deficit following operation on the second side led to the only death (0.6%) in this series. Both neurological deficits (one temporary and one permanent) following the second endarterectomy occurred after procedures staged more than 60 days apart. No differences in mean SBP and DBP existed between patients with and without neurological deficits. Statistical analysis of SBP and DBP recordings during and 6, 12, 24, and 36 hours after operation when the two were staged 7 days (nine patients), 8 to 14 days (five patients), 15 to 30 days (10 patients), 30 to 60 days (17 patients), and more than 60 days (38 patients) apart revealed significantly higher readings after the second procedure, only in patients staged greater than 60 days (P less than 0.05). Therefore, in our experience, neurological deficits were less common after the second endarterectomy, and, although postoperative blood pressures were higher after the second side, these were significant only in patients staged more than 60 days apart. We find no evidence to suggest that increasing the waiting period between bilateral procedures will lower the incidence of undesirable neurological sequelae.