The development and evolution of polyembryonic insects.
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Biomedical subjects
Publications and source records attributed to M Grbic.
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THe polyembryonic wasp Copidosoma floridanum produces up to 2000 individuals from a single egg. During the production of individual embryos the original anteroposterior axis of the egg is lost and axial patterning must subsequently be reestablished within each embryo. The mechanism by which this occurs is unknown. In most insects, egg polarity is established during oogenesis and early development takes place in a syncytium. In Drosophila melanogaster, the syncytium is considered essential for establishing the morphogenetic gradients that initiate segmental patterning. However, we found that development of C. floridanum occurs almost exclusively in a cellularized environment. To determine whether the D. melanogaster patterning cascade is conserved in the absence of a syncytium, we analyzed the expression of Even-skipped, Engrailed and Ultrabithorax/Abdominal-A during polyembryonic development. Here we show that in spite of the absence of a syncytium, the elements of the D. melanogaster segmentation hierarchy are conserved. The segment-polarity gene Engrailed and the homeotic genes Ultrabithorax/Abdominal-A are expressed in a conserved pattern relative to D. melanogaster. However, we detect an alteration in the expression of the Even-skipped antigen. Even-skipped is initially expressed in segmentally reiterated stripes and not in the pair-rule pattern as it is in D. melanogaster. We also observe that the expression of these regulatory proteins does not occur during the early proliferative phases of polyembryony. Our results indicate that a syncytium is not required for segmental patterning in this insect.
OBJECTIVE: To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. DESIGN: Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. PATIENTS: 20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. RESULTS: The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). CONCLUSIONS: Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.
Left atrial (LA) function was studied in 32 patients during percutaneous transluminal coronary angioplasty of the proximal left anterior descending artery with a dual micromanometer positioned transseptally in the left atrium and in the left ventricle. In 10 patients LA and left ventricular (LV) cineangiography was performed 30 minutes before percutaneous transluminal coronary angioplasty and 30 seconds after the occlusion of the left anterior descending coronary artery. Thirty seconds after left anterior descending occlusion, LV peak systolic pressure decreased from 135 +/- 12 to 106 +/- 9 mm Hg (p less than 0.05) and LV maximum dP/dt decreased from 1,634 +/- 136 to 1,137 +/- 127 mm Hg/s (p less than 0.01). Simultaneously, LA mean pressure increased from 11 +/- 2 to 29 +/- 1 mm Hg (p 177 +/- 13 to 381 +/- 21 mm Hg (p less than 0.001). There was a difference between LV end-diastolic pressure and LA mean pressure of 1.5 mm Hg at rest and 7.8 mm Hg during ischemia and LA pulse pressure increased from 16 +/- 3 to 26 +/- 3 mm Hg (p less than 0.05) together with increase of LA A and V waves peak pressure. LV stroke volume index decreased from 46 +/- 5 to 43 +/- 3 ml/m2 (difference not significant). The LA maximal volume increased from 18 +/- 2 to 29 +/- 3 ml/m2 (p less than 0.001). LA volume before LA contraction increased from 29 +/- 2 to 54 +/- 3 ml/m2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
100 patients who had undergone successful coronary angioplasty were followed up for 12, 42 and 84 months. The mean age of the population was 53 +/- 10 years and 89 were males. 86 patients had single vessel coronary artery disease and 14 multi-vessel disease. 9 patients had had previous by-pass surgery. Coronary angioplasty was done on 54 left anterior descending, 28 right and 9 left circumflex coronary arteries, and 9 by-pass grafts. Follow-up comprised clinical examination, stress test and personal evaluation by the patients. There was a clear-cut improvement in 66% of patients after 1 year, in 84% at 3 1/2 years and 26% at 8 years, excluding 6 deaths and 9 patients undergoing by-pass surgery. Improvement was moderate in 24% of patients at 1 year, 16% at 3 1/2 years and 58% at 8 years. Stress test was negative in 50% of patients at 1 year, in 64% at 2 years and in 70% at 3 1/2 years. At the latest follow-up (8 years) 6 patients had died, 5 had undergone by-pass surgery and 26 had undergone a further coronary angioplasty; 26% of these 84 patients were symptom free, 58% in class I, 9% in class II, 5% in class III and 2% in class IV (New York Heart Association classification). In conclusion there was a clearcut longterm improvement after coronary angioplasty, thus making this technique the first choice treatment in coronary artery disease in patients with suitable coronary lesions.
Left ventricular contractility and relaxation in mitral stenosis are still controversial. 20 patients with pure mitral stenosis in sinus rhythm have been studied during diagnostic cardiac catheterization with high fidelity pressure and output recording at rest (R), during dynamic exercise (E), handgrip (HG), methoxamine infusion (M) and amyl nitrite inhalation (AN). - The results were as follows: Mitral valve area was 1.2 +/- 0.4 cm2 and did not change during interventions. LV end-diastolic volume were 106.3 +/- 19.6 ml and ejection fraction 66.5 +/- 3.2%. The mitral valve opening occurred irrespective of interventions 37 +/- 2 msec after left ventricular and left atrial pressure crossover. The mitral valve opening was followed by left ventricular negative pressure of -4.6 +/- 1 mm Hg, suggesting active left ventricular suction. This negative protodiastolic pressure was accentuated by the premature ventricular beat (-7.2 +/- 2.0 mm Hg), AN (-7.4 +/- 1.8 mm Hg) and M infusion (-7.4 +/- 1.2 mm Hg). Closure of the mitral valve occurred 10-15 msec after left ventricular and left atrial pressure crossover, and thus the first part of left ventricular contraction is "non-isovolumic". The LV-LA diastolic pressure gradient at R (15 +/- 7 mm Hg) rose during AN (20 +/- 7.8 mm Hg) and E (28 +/- 8 mm Hg) and remained unchanged during M (15 +/- 6 mm Hg). LV end-diastolic pressure was normal (6.5 +/- 2.4 mm Hg), unchanged during E (6.6 +/- 2.7 mm Hg), diminished during AN (3.6 +/- 1.3 mm Hg) and rose during M (16 +/- 5.8 mm Hg). The peak rate of rise of LV pressure (max dP/dt) was a little low at R (1163 +/- 236 mm Hg/sec) but rose normally on E (1860 +/- 503 mm Hg/sec) and did not change on M (1177 +/- 180 mm Hg/sec), suggesting normal systolic function.
Balloon angioplasty fails to provide acceptable long-term results for a significant proportion of patients. An intravascular mechanical support, developed with the aim of preventing restenosis and acute closure of diseased arteries after transluminal angioplasty, was implanted in 44 patients (39 male and five female), aged from 35 to 70 years (mean 56 years) with documented restenosis of native coronary artery (41 stents) and bypass grafts (12 stents). In the group of bypass graft patients there was no local restenosis and no major complication. In patients in whom stents were placed in native coronary arteries, the complication rate was higher (two patients died after coronary bypass surgery). One patient died suddenly at home. Except for one patient, in whom a new lesion developed proximally with extension into the stent, no case of restenosis could be observed. Despite the still relatively high complication rate, we feel that stenting may present a rational approach to the unresolved problem of restenosis after coronary angioplasty.
25 patients with acute myocardial infarction pain lasting more than 20 minutes which was not relieved by nitrates, whose ECGs showed ST segment elevations of 1 mm or more in 2 or more ECG leads, and who presented less than 3 hours after onset of their symptoms were randomly assigned to one of 2 thrombolytic treatment groups: a single intravenous bolus of anisoylated plasminogen streptokinase activator complex (APSAC) 30U in 5 minutes or an intravenous infusion of streptokinase 1,500,000U over 60 minutes. 3 to 4 hours after the administration of the thrombolytic agent, all patients received intravenous heparin at full dosage for 24 hours. The patency of the infarct-related coronary vessels was assessed by angiography 1 to 4 hours after administration of the thrombolytic agent. Clinical signs, ECGs, pulse, blood pressure and temperature were monitored regularly for 24 hours after treatment or as clinically appropriate. APSAC seemed to be at least as effective as streptokinase in terms of patency of the infarct-related vessel (92% vs 63%, respectively). The adverse events were similar and none was life-threatening. APSAC and streptokinase caused similar falls in blood fibrinogen levels. APSAC, given as a bolus injection over 5 minutes, was easier to administer than streptokinase, which was given as an infusion during 60 minutes.
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A case is reported of a previously healthy 16-year-old boy who developed a rapid atrial fibrillation following a minor thoracic impact. This tachyarrhythmia resistant to several drugs responded immediately to administration of flecainide. The restoration of sinus rhythm led to diagnosis of type A Wolff-Parkinson-White syndrome.
The effectiveness and safety of flecainide and quinidine for conversion of atrial fibrillation (AF) to sinus rhythm were compared. Sixty consecutive patients were treated with either flecainide (up to 2 mg/kg intravenously and then orally) or quinidine (up to 1.2 g orally). There was no statistical difference in age, left atrial size, duration of the arrhythmia and underlying cardiac diseases between the 2 groups. The overall conversion rate to sinus rhythm was 63% (38 patients): AF was converted in 18 patients (60%) treated with quinidine and 20 (67%) with flecainide. If AF lasted less than 10 days, the conversion rate was 86% in the flecainide group and 80% in the quinidine group (difference not significant). When AF lasted more than 10 days the rate was 22% in the flecainide group and 40% in the quinidine group. Adverse effects were more frequent in the quinidine group (27%) (gastrointestinal disturbances) than in the flecainide group (7%) (conduction disturbances), but they were less severe in the quinidine group. Thus, flecainide given intravenously appeared to be as effective as quinidine given orally for conversion of AF of recent onset (within 10 days). However, quinidine should probably remain the preferred drug for conversion of AF of long duration (more than 10 days) to sinus rhythm. Adverse effects occurred less often with flecainide therapy, but they were more severe.
Mitral valve prolapse frequently resembles coronary heart disease. Retrospective clinical, ECG and angiographic analysis of 100 consecutive patients with mitral prolapse and normal coronary arteries, but complaining of anginal pain, shows how difficult it is to establish the correct diagnosis. When resting, 44% of patients have nonspecific ECG disorders of repolarization phase. During periods of chest pain 3 patients experienced transient ST segment changes very similar to acute myocardial ischemia. The exercise test was positive in 39% of cases, and in 2 patients during exercise a sudden drop in blood pressure suggested coronary perfusion failure. In all patients the coronary arteries were normal, but left ventriculography showed mitral valve prolapse predominantly on the posterior leaflet. At rest, 35% of patients had diastolic compliance failure, 32% had left ventricular hyperkinesia and only in 3% was slight hypokinesia present. Finally, early systolic relaxation of the anteroapical wall was observed in 75% of patients.
Acute occlusion of the left main coronary artery is normally fatal. According to the literature, only a few cases have been treated by intracoronary thrombolysis; the prolonged period of ischemia, however, resulted in severe left ventricular dysfunction and numerous complications. Therefore, effort should be directed to recanalize the left main coronary artery within the shortest possible interval. We followed this approach in a case of acute occlusion of a subtotal stenosis of the left main coronary artery which could be mechanically reopened and dilated within a few minutes. The intervention resulted in immediate reversal of profound cardiogenic shock and complete restoration of normal left ventricular function. At hospital discharge, the patient was asymptomatic with a negative bicycle stress test. Immediate mechanical recanalization and angioplasty appear to be a feasible approach in life-threatening coronary occlusion.
Coronary occlusion is the most serious complication of percutaneous transluminal angioplasty. In 440 cases coronary occlusion occurred in 22 patients (5%). Treatment was coronary bypass in 12 cases mechanical recanalization in 7 cases and coronary bypass after unsuccessful mechanical recanalization in 3 cases. One patient died after mechanical recanalization and 9 (41%) had myocardial infarction confirmed by electrocardiography and angiography. The number of coronary occlusions increased initially but decreased with improvements in materials and techniques. It is concluded that coronary occlusion is a severe but rare complication of percutaneous angioplasty. Mechanical recanalization should be attempted, and in case of failure the patient should be referred for surgery. In the large majority of cases the outcome is benign.
The time between coronary artery occlusion and reperfusion remains the decisive factor for myocardial function in acute myocardial infarction. Of 110 patients admitted to hospital less than 3 hours after the onset of chest pain, 83 underwent intracoronary thrombolysis with streptokinase or urokinase. 27 patients underwent mechanical recanalization with the aid of a steerable guide wire (Schneider 0.014") followed by transluminal angioplasty of the residual stenosis. 70 of 83 patients (84%) were recanalized by intracoronary streptokinase perfusion within 45 +/- 10 minutes. By mechanical recanalization the occluded artery could be recanalized in 27 patients within 6 +/- 1 minutes. During the same session transluminal angioplasty was performed while the affected coronary artery was perfused for 20 minutes with 20,000-50,000 U streptokinase. 2 patients died after intracoronary thrombolysis (2.4%) and 1 patient died after mechanical recanalization (3.7%). 25 of 26 survivors of the mechanical recanalization group were discharged after bicycle stress testing, and 1 patient underwent a coronary bypass operation. In the intracoronary thrombolysis group, 4 patients presented with reobstruction of the affected vessel within 24 hours of the intervention (4.8%). Of the remaining 66 patients. 20 underwent transluminal coronary angioplasty (285), 16 coronary bypass (22%) and 30 received drug therapy (43%). Left ventricular injection fraction, measured 24 hours after treatment, was 63 +/- 10% in the mechanical recanalization group and 53 +/- 9% in the intracoronary thrombolysis group.
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We evaluated the efficacy of flecainide acetate (given intravenously to a maximal dose of 2 mg kg-1 and then orally in a dose of 100 mg b.d. or 100 mg t.d.s.) in the conversion to sinus rhythm of 50 patients exhibiting supraventricular arrhythmias (39 with atrial fibrillation, 6 with atrial flutter, 4 with supraventricular tachycardia and one with supraventricular tachycardia in association with the Wolff-Parkinson-White syndrome). Conversion was achieved in 36 patients (72%) (29 cases with atrial fibrillation, 4 cases with supraventricular tachycardia, 2 cases with atrial flutter and one case with Wolff-Parkinson-White syndrome), over a mean period of 7.4 +/- 9 h. The patients in which conversion was achieved had arrhythmias which had been in existence for a shorter time (5.3 +/- 9.8 days) than those in which conversion was not achieved (16.7 +/- 26.2 days) (P less than 0.01). The mean dosage of flecainide used to achieve conversion was 2.5 +/- 2.36 mg kg-1. Flecainide appears to be an effective agent for the conversion to sinus rhythm of atrial fibrillation and supraventricular tachycardias. Its efficacy in cases of atrial flutter has not yet been demonstrated.