[Prognostic evaluation of a patient with acute anuria].
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Biomedical subjects
Publications and source records attributed to K Rasmussen.
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The effects of administration of the non-benzodiazepine anxiolytic buspirone on the spontaneous and sensory evoked single unit activity of serotonergic (5-HT) neurons in the dorsal raphe nucleus and noradrenergic (NE) neurons in the locus coeruleus were examined in freely moving cats. Buspirone (1.0 mg/kg i.p.) strongly suppressed both the spontaneous and evoked activity of 5-HT dorsal raphe nucleus neurons. The spontaneous activity of NE neurons in the locus coeruleus was non-significantly increased by drug administration, while the evoked response was unaffected. These effects occurred during a period of mild behavioral activation. It is suggested that the anxiolytic effects of buspirone administration are not achieved through an action of NE neurons, but may be mediated in part by actions on 5-HT neurons in the dorsal raphe.
One hundred ninety patients with chronic angina for an average of 2 years were followed. Forty-seven had at least 1 mm of ST deviation in response to provocation of coronary vasoconstriction by prolonged hyperventilation (group I); 143 had no ST deviation (group II). The angiographic response to this test was studied in 21 patients from group I, and revealed 25 to 100% diameter reduction; in group II 9 patients showed a 5 to 14% diameter reduction. In group I, 15 patients (32%) died (hazard rate = 0.17 deaths/patients X years) vs 18 (13%) in group II (hazard rate = 0.06) (p less than 0.01). Seven patients in group I (15%) and 3 in group 2 (2%) died while waiting for surgery (p less than 0.01). All patients who died had coronary stenoses of at least 70%. A Cox regression analysis, using 24 variables (invasive and noninvasive), showed a positive hyperventilation test (ST deviation at least 1 mm), low ejection fraction and systolic blood pressure of at least 160 mm Hg to be independent predictors of death (p less than 0.05). Considering only deaths in non-operated patients (patients waiting for surgery and patients not planned to undergo operation), a rate-pressure product/100 of 150 or less at exercise stress testing, left ventricular end-diastolic pressure of 15 mm Hg or more and duration of angina less than 1 year were also independent predictors of death. Thus, the hyperventilation test may be useful for identifying angina patients who are at high risk of cardiac death due to dynamic coronary obstructions.
Evidence from this and other laboratories has suggested that the nuclear binding sites (acceptor sites) for steroid receptors on chromatin involves chromatin protein-DNA complexes. A saturable high affinity receptor-dependent nuclear binding to these sites by isolated steroid receptor complexes has been reported. Addition of nonradiolabelled progesterone receptor from the chicken oviduct (PRov) successfully competes for the [3H]PRov binding to these acceptor sites in isolated chromatin or in nucleoacidic protein (NAP), a partially deproteinized chromatin enriched in these binding sites. This competition does not occur with pure DNA. This laboratory has isolated and enriched the chromatin proteins (acceptor proteins) involved in the nuclear acceptor sites for the avian oviduct PRov. Monoclonal antibodies against the nuclear acceptor sites for the PRov have been prepared using highly purified hen oviduct acceptor proteins reconstituted to hen DNA. Addition of the MAbs to a cell-free assay blocks PR binding to native oviduct chromatin as well as to NAP. However, the antibodies do not block PR binding to pure DNA nor do they affect the receptor itself. A partial animal species specifically was observed with the Ab inhibition of the PR binding, whereas no tissue specificity was seen. Direct binding of the antibodies to native acceptor sites was demonstrated using an ELISA system. The antibodies showed little recognition of free acceptor protein or DNA alone, indicating specificity for the protein-DNA complex. The partial evolutionary conservation of the nuclear acceptor sites for PR, as shown by the inhibition of PRov binding, was further supported by the partial crossreactivity of the MAbs with the NAPs from the same animal species using the ELISA. These data support earlier studies using PR binding assays showing that: 1) the reconstituted PR acceptor sites resemble the native sites; 2) the sites on whole chromatin and on NAP are similar; 3) the PR binding sites of chromatin and NAP are different from those of pure DNA; and 4) the nuclear acceptor sites for PR are different from those of the estrogen receptor. These results support a receptor specificity of the PR acceptor sites as reported previously using direct receptor competition studies.
We induced coronary vasoconstriction by hyperventilation for 6 minutes (arterial pH = 7.6 +/- 0.06) and ergometrine (0.4 mg) in 24 patients suspected of coronary vasospasm. ST deviation greater than or equal to 1 mm was induced in 12 patients by hyperventilation and in 10 by ergometrine. Using spontaneous ST deviation as the independent reference the sensitivity of hyperventilation was 86% and the sensitivity of ergometrine 77%. Ergometrine caused sinus bradycardia and hypotension in 3 patients; hyperventilation caused no untoward reactions. In 12 of the patients coronary angiogram and wedge pressure were obtained during provocative testing. A computer-assisted analysis of coronary diameters in 43 arterial segments (3-4 per patient) showed a 16 +/- 12.6% and 14 +/- 16.7% reduction after hyperventilation and ergometrine, respectively. The maximal coronary diameter reduction induced by hyperventilation and ergometrine was 26 +/- 13.9% and 28 +/- 15.0%, respectively, and showed a significant correlation between the two tests (r = 0.77, N = 12, P less than 0.01). The wedge pressure increase induced by hyperventilation correlated to the maximal coronary diameter reduction (r = 0.63, N = 12, P less than 0.05), while no such correlation was found by ergometrine testing. We conclude that hyperventilation leading to arterial pH about 7.6 has essentially the same potency as 0.4 mg ergometrine, but the hyperventilation test appears to be safer.
The precision of the Doppler method for quantitative blood flow measurement in the fetal descending thoracic aorta and in the umbilical vein and for estimation of the Pulsatility Index from the velocity curve from fetal aorta was tested in vivo by examination of six pregnant women eight times. Two investigators examined each patient twice in random order upon two successive days. The diameter of the vessel was measured using planimetry on a magnified time-motion image of the diameter variations during the heart cycle, while the angle between the ultrasound Doppler beam and the vessel of interest was measured on the hard copy image. No systematic variation was found between observers, days, repeated observations or repeated readings of curves and images. The mean coefficient of variations was 5.6% for the quantitative flow per kilogram estimated fetal weight measured in the fetal descending aorta, 6.8% for the quantitative flow per kilogram estimated fetal weight measured in the umbilical vein and 9.8% for the Pulsatility Index. When the diameter of aorta was calculated as the mean of the maximal and the minimal diameter measured on the hard copy image, the mean coefficient of variation for the flow increased to 9.4%. In vitro tests of the Doppler instrument and the real-time scanner revealed a systematic overestimation of Doppler measured flow of only 4.4% compared with the true flow, and a real-time scanner underestimation of vessel diameter of only 1.1%.
Among 400 consecutive patients undergoing conventional isolated bypass surgery, 9 patients had clinical and electrocardiographic evidence of severe ischaemia during exercise and serious exercise-induced ventricular arrhythmias. Four patients had spontaneous exercise-induced arrhythmias and two had been resuscitated for out-of-hospital cardiac arrest. Postoperatively all patients were free of angina, off anti-anginal drugs with considerably increased exercise capacity and maximal heart rate during exercise. No spontaneous or exercise-induced arrhythmias have recurred during observation periods ranging from one to four and a half years. In this subset of patients ischaemia seems to be the crucial arrhythmia-inducing factor and bypass surgery alone may therefore be therapeutic. The reduction of ischaemic exercise-induced arrhythmias may be one way by which bypass surgery reduces mortality in larger patient series.
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The response to prolonged hyperventilation (HVT) was evaluated by electrocardiography (HVT-ECG) and thallium-201 myocardial scintigraphy (HVT-Tl-Sc) in 40 patients suspected of vasospastic angina. Both tests showed ischaemic changes in 16 patients and no changes in 20 patients. Two patients had abnormal HVT-ECG and normal HVT-Tl-Sc, and the reverse combination was found in two patients. Prolonged HVT was performed in 14 patients during coronary angiography (CAG). Nine developed transient total or subtotal occlusion in one of the major coronary arteries, all of whom had ischaemic HVT-ECG and eight had abnormal HVT-Tl-Sc. In the five patients without spasm at CAG four had normal HVT-ECG and all five normal HVT-Tl-Sc. Our data suggest that HVT-ECG and HVT-Tl-Sc have essentially the same sensitivity and specificity in detecting vasospastic angina.
Left ventricular aneurysmectomy was performed on 45 men and 12 women (mean age 57 years) during a 12-year period. The hospital mortality was 14% and the cumulative 5-year survival 57% +/- 9 (SE). Of 35 survivors, 33 underwent a follow-up study (mean 28 months post-operatively). The mean cardiothoracic index fell from 0.58 +/- 0.08 (SD) to 0.51 +/- 0.04 and the mean left ventricular ejection fraction (EF) improved from 0.30 +/- 0.08 to 0.38 +/- 0.01 (both changes significant). Echocardiographic parameters showed no significant improvement in left ventricular function. The NYHA classification was I or II in 85% of the patients at follow-up, but in only 23% preoperatively. Preoperative EF greater than or equal to 0.30 was associated with 76% +/- 16 (SE) cumulative 5-year survival as compared with 31% +/- 12 when EF had been less than 0.30. In view of these results, left ventricular aneurysmectomy should be recommended for all symptomatic patients.
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Quantitative blood flow in the fetal descending thoracic aorta and in the umbilical vein was measured both in a longitudinal study where each of 13 fetuses was examined three times and in a cross-sectional study where 45 fetuses were examined once only in the last trimester of normal pregnancy. The waveform of the velocity curves from fetal descending aorta was examined and the Pulsatility Index, the A/B ratio and the least diastolic velocity were calculated. The longitudinal study showed that all these parameters and the fraction of the flow in the fetal descending aorta, which was distributed to the placental circulation, were constant during the last trimester. The problems of longitudinal inference from cross-sectional studies are discussed. For all 58 fetuses the flow in the descending thoracic aorta was 234 ml/min/kg and in the umbilical vein 127 ml/min/kg. The Pulsatility Index was 1.83, the A/B ratio 4.75, the least diastolic velocity 9.9 cm/s. The fraction of blood flow in the descending aorta distributed to the placental circulation was 55%.
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The haemodynamics of fetuses of 15 pregnant women who developed hypertension during the last trimester of pregnancy were investigated before and after antihypertensive treatment using the ultrasound-Doppler method for non-invasive measurements of blood flow, and the results were compared to those from investigations of fetuses from normal pregnancies. In the untreated condition, significant reduction of blood flow was demonstrated in the fetal descending aorta (p less than 0.01) and in the umbilical vein (p less than 0.02). The resistance to flow, expressed as the Pulsatility Index, was significantly elevated (p less than 0.001). A significant correlation was shown between Pulsatility Index and maternal diastolic blood pressure (p less than 0.001) and a significant negative correlation between blood velocity in fetal aorta and maternal diastolic blood pressure (p less than 0.01). Treatment resulted in significant reduction of resistance to flow, which remained normal for the rest of the pregnancy. It is concluded that fetal haemodynamics are affected by maternal hypertension during pregnancy. The results suggest that the fetus also suffers from hypertension. Therapy with oral alpha-methyldopa and labetalol combined with volume expansion with human albumine normalised fetal circulation and kept it normal for the remainder of the pregnancy.
The rank order of potency for the physiological effects of three phenethylamine hallucinogens in the locus coeruleus (LC) was identical to that previously shown for their 5-HT2 binding affinity [-) DOB greater than DOM greater than ( + )DOB). The behaviorally inactive positional isomer of DOB, SL-7161, did not significantly affect LC unit activity. These results offer insight into structure-activity relationships at 5-HT2 receptors and support earlier findings that the actions of hallucinogens displayed in the LC are mediated via 5-HT2 receptors.
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As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) (20-80 micrograms/kg) was found to have similar effects. Systemic administration of the selective 5-HT2 antagonists LY 53857 (0.02-0.8 mg/kg) and ritanserin (0.1-0.3 mg/kg) completely reversed both actions of the hallucinogens on the LC. In contrast, LY 53857 did not reverse the effects of (+)-amphetamine (0.5 mg/kg) on the spontaneous or sensory-evoked activity of the LC. These results suggest that the common actions of indoleamine and phenethylamine hallucinogens displayed in the LC are mediated via 5-HT2 receptors; however, these receptors appear to be located outside the LC itself.