Depression and cancer: an update.
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Biomedical subjects
Publications and source records attributed to F Fernandez.
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Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals and in humans. We have previously observed that the thrombolytic effect of t-PA persists beyond its time of clearance from the circulation and that wound bleeding induced by a high dose infusion of t-PA is delayed for at least one and a half hours after commencing the infusion. These observations suggest that improved thrombolysis may be obtained with t-PA by infusing a high dose over a short period of time. To test this hypothesis we compared the thrombolytic and hemorrhagic effects of t-PA infused over 240, 60, 30 and 15 minutes in the rabbit. A 4 hour infusion of 30,000 U/kg of t-PA produced 36% thrombolysis. The same dose of t-PA infused over 60, 30 and 15 minutes produced 87%, 88% and 96% thrombolysis, respectively (p less than 0.01). The 1 hour infusion of 30,000 U/kg of t-PA produced a significant increase in blood loss relative to saline infusion (p less than 0.01). The same dose infused over 30 and 15 minutes did not produce significantly more bleeding than saline. A higher dose of t-PA, 60,000 U/kg, infused over 4 hours, produced 95% thrombolysis, but was associated with a significant increase of blood loss (p less than 0.001). Our findings suggest that improved thrombolysis with t-PA with minimal bleeding side-effects is achieved in rabbits when t-PA is administered in a relatively high dose given over a short period of time.
A novel fat-soluble vitamin K like molecule was isolated from the prokaryote, Eubacterium lentum, and its structure investigated by mass spectrometry and proton nuclear magnetic resonance spectrometry. On the basis of these studies the novel quinone is shown to be 2,5 and 6- or 2,7 and 8-trimethyl-3-farnesylfarnesyl-1,4-naphthoquinone.
A percutaneous method via the brachial artery for left heart catheterization and selective coronary angiography is described. The technique uses the sheath intended for the femoral artery, continuously infused and introduced following a particular technique. The procedure was performed with minimal complications over 18 months, with multipurpose "Schoonmaker" or preshaped catheters, in all the patients (37) in whom the femoral approach was contraindicated or failed. When a catheterization must be performed from the arm, this method, without cutdown and arteriotomy and allowing a good distal flow during the procedure, appears to have some advantages over the classical Sones technique or the percutaneous arterial axillary approach.
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This study demonstrates that a low haematocrit is the main determining factor of the prolonged bleeding time often encountered in uraemic haemodialysed patients. Thirty-three patients submitted to regular haemodialysis and having a platelet count greater than 100 X 10(9)/l were investigated with the following tests: simplate bleeding time, blood cell count, platelet aggregation induced by ADP, collagen and sodium arachidonate, arachidonate induced MDA synthesis, tests for detection of an acquired storage pool disease, and factor VIII complex level. The results were compared to two other groups; one of uraemic patients not yet subjected to haemodialysis and another of healthy volunteers. The results were basically identical in the two groups of uraemic patients. The only consistent abnormality was a 30-35% reduction in the platelet MDA synthesis in comparison with control subjects. There was a negative correlation between the log bleeding time and the haematocrit (r = 0.78, P less than 0.01). Fourteen uraemic patients having a prolonged bleeding time were submitted to a red cell transfusion programme and were investigated a second time under identical conditions. There was no change in any of the platelet function tests or in the factor VIII complex level, but the bleeding time was normalized when the post-transfusion haematocrit was over 26% (nine patients). This study emphasizes the role of anaemia in the pathogenesis of the prolonged bleeding time in uraemia and suggests that red cell transfusion can be a long-term efficient therapeutic measure to stop bleeding in these patients.
Tissue-type plasminogen activator (t-PA) is a promising thrombolytic agent because it can produce thrombolysis without inducing a plasma proteolytic state. It is uncertain if this potentially important feature renders t-PA less hemorrhagic than other plasminogen activators. We have compared the hemorrhagic and thrombolytic effects of t-PA and streptokinase in rabbits. Streptokinase, 4000 U/kg/hr over 4 hr, failed to produce significant thrombolysis and 8000 U/kg/hr streptokinase over 4 hr produced only 28 +/- 6% thrombolysis. Both streptokinase regimens were associated with a plasmin-mediated plasma proteolytic state and both streptokinase regimens produced a significant increase in hemorrhage that was evident within 15 min of beginning the infusion and was progressive over the 4 hr of drug administration. In contrast, t-PA in a dose of 7500 U/kg/hr produced 35 +/- 6% thrombolysis, but it did not produce a plasmin-mediated plasma proteolytic state or a significant increase in hemorrhage over the 4 hr of infusion. t-PA in a dose of 15,000 U/kg/hr produced 85 +/- 4% thrombolysis but was associated with a plasmin-mediated proteolytic state and produced significant bleeding which, in contrast to streptokinase-induced bleeding, was delayed in onset. Therefore, t-PA induced less hemorrhage than streptokinase at doses that produced more effective thrombolysis. Bleeding with both thrombolytic agents was associated with a plasmin-mediated proteolytic state.
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The M mode echocardiographic recordings of 52 normal mitral bioprostheses (NMB), 7 pathological mitral bioprostheses (PMB), 30 normal aortic bioprostheses (NAB) and 10 pathological aortic bioprostheses (PAB) were reviewed. In normal bioprostheses a significant correlation was observed between the echocardiographic and the "specified" diameters, the diastolic and systolic slopes and the amplitude of anterior motion of the support. In NMB, the end-systolic diameter of the left ventricular outflow tract depended on the "specified" diameter of the bioprosthesis. Paradoxical septal motion was observed in 78 p. 100 of cases. In PMB, the velocity of anterior leaflet opening was significantly increased (p less than 0.001). The end-diastolic internal left ventricular dimension was also increased (p less than 0.01). A significant correlation was found between left ventricular fractional shortening and maximal leaflet separation (p less than 0.05). Normal septal motion was more common (p less than 0.05). In 5 cases of prosthetic valve dysfunction with mitral regurgitation the maximal leaflet separation was greater than normal (p less than 0.001), the diastolic slope of the support was increased (p less than 0.05) and diastolic vibrations of thickened irregular leaflets were observed. Systolo-diastolic vibrations with chaotic leaflet motion were characteristic of cusp tear and/or eversion. Stratified echos behind a support with reduced leaflet excursion was observed in one case of partial thrombosis: a thickened systolic echo with reduced diastolic excursion was observed in a case of degenerative stenosis. The review of 10 PAB showed a reduced amplitude of systolic excursion of the anterior support in cases of aortic regurgitation (p less than 0.05). Systolic vibrations of the cusp were not specific and were observed in normal cases. In severe valvular regurgitation mitral and/or septal diastolic fluttering was observed. Systolic excursion of the cusps was reduced in cases of relative stenosis due to an inappropriately small sized bioprosthesis. Thickening of the diastolic cusp echos was observed in cases of degenerative stenosis. Ventricular dilatation and reduced septal and free wall motion were dysfunction.
Twenty-five patients with hypertrophic obstructive cardiomyopathy confirmed by clinical, echocardiographic and haemodynamic investigations were treated with high dose propranolol (320 to 800 mg/day, average 420 mg/day) and assessed after an average follow-up period of 25 months. The effects of treatment were assessed by interrogation in all patients and by exercise testing before and after propranolol in 19 cases. Comparative echocardiographic (21 patients) Holter (20 patients) and catheter studies (14 patients) were also performed. The cardiovascular mortality rate during the study period was nil. All patients were symptomatic before treatment; 9 became asymptomatic and 13 patients were improved, the average functional score decreasing from 5.16 +/- 2.15 to 2.28 +/- 1.49 (p less than 0.001). The persistence of severe symptoms led to withdrawal of the beta-blocker in 2 cases. There was a parallel improvement in maximal work capacity during exercise stress testing (96 +/- 27 watts vs 117 +/- 30 watts, p less than 0.01). A resting intraventricular pressure gradient was recorded in 12 of the 14 patients undergoing repeat catheter study which decreased after propranolol from an average of 66.75 +/- 32.72 mmHg to 42.75 +/- 37.6 mmHg (p less than 0.05). Left ventricular end diastolic pressures remained unchanged. The change in pressure gradient did not correlate with the symptomatology and there were no associated echocardiographic changes. The Holter monitoring did not show any improvement of ventricular hyperexcitability under propranolol: the number of patients with complex ventricular arrhythmias remained unchanged (7 patients).(ABSTRACT TRUNCATED AT 250 WORDS)
Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t-PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
A simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient's platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient's platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.
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Three-hundred-and-thirty lateral skull-films obtained from apparently healthy normocephalic Jamaican children between the age of one month and five years were studied, using bony reference points nasion (N), tuberculum sellae (Ts), internal occipital prominence (IOP), inion (I), bregma (B) and lambda (L). Cranial-base length was measured between N-Ts, Ts-IOP and N-I. Calvarial height was measured between Ts-B (anterior calvarium) and Ts-L (posterior calvarium). All the measurements showed an increase with age and were higher in boys. Significant correlations were seen between N-Ts and Ts-IOP, N-Ts and N-I, N-Ts and Ts-B, N-Ts and Ts-L and N-I and Ts-L at all the ages and in both sexes. Ratios between lengths of anterior and posterior cranial-base, as well as between cranial-base lengths and anterior cranial heights, were nearly constant at all the ages and in both sexes. These observations support the view that there is definite proportionality between the growth of anterior and posterior cranial-base lengths, and between anterior calvarial height and cranial-base lengths. On the other hand, a significant increase with age was seen in the ratios N-Ts/Ts-L, N-I/Ts/L and Ts/B/Ts-L, suggesting a progressive decrease in growth of posterior calvarial height. A comparison of the data with previously published figures for Indian and Norwegian populations suggests a racial difference in the various cranial-base and calvarial ratios.
Forty-nine cases of Wolff-Parkinson-White syndrome (WPW) were diagnosed out of 10 750 patients with cardiac disease (0.45 p. 100), 24 cases out of 3 761 congenital malformations and 25 cases in the 6 989 patients with acquired heart disease. Right ventricular pre-excitation was recorded in 31 cases; 13 in the lateral zone, 12 in the posterior paraseptal zone and 6 in the anterior paraseptal zone. Left ventricular pre-excitation was recorded in 18 cases: 8 in the lateral zone, 5 in the anterior paraseptal and 5 in the posterior paraseptal zones. WPW and congenital heart disease: Out of 20 cases of Ebstein's anomaly, 5 cases of WPW were observed: 4 right posterior and 1 right lateral pre-excitations. Out of 218 cases of hypertrophic obstructive cardiomyopathy, 7 cases of WPW were observed, 4 of which were congenital. Three cases of WPW were recorded in 699 patients with ventricular septal defects. Out of 1 348 cases of atrial septal defect, 5 cases of pre-excitation were recorded, including 3 right posterior pre-excitations associated with an ostium primum defect. Pre-excitation was also observed in isolated cases of corrected transposition of the great arteries, supravalvular aortic stenosis, aortic incompetence and patent ductus arteriosus. Pre-excitation and acquired heart disease: Five cases of pre-excitation were recorded out of 305 cases of dilated cardiomyopathy (1.62 p. 100). Eleven cases of pre-excitation were recorded in a total of 3 471 cases of valvular heart disease (0.31 p. 100): 9 in rheumatic valve disease and 2 in mitral valve prolapse. Nine cases of pre-excitation were observed in 2 850 cases of coronary artery disease. Intermittent Wolff-Parkinson-White syndrome: Ventricular pre-excitation masks the ECG changes of complete right bundle branch block in Ebstein's anomaly, complete left bundle branch block in aortic incompetence and dilated cardiomyopathy, and the in-complete right bundle branch block often seen in mitral valve prolapse. The characteristic appearances of WPW depend on the zone of pre-excitation. Right ventricular hypertrophy observed in ventricular septal defect with pulmonary stenosis and mitral stenosis may be masked by right lateral pre-excitation. Changes of inferior wall myocardial infarction may be masked by left anterior wall pre-excitation. On the other hand, the effects of WPW on left ventricular hypertrophy are variable, high amplitudes of the resultant forces seeming to depend on late and isolated activation of one of the left ventricular walls.
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