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Biomedical subjects

L Guarino

Publications and source records attributed to L Guarino.

At least 19 recordsLinked to original sources

Construction, expression, and characterization of a baculovirally expressed catalytic domain of human matrix metalloproteinase-9.

We report DNA construction, baculovirus expression, and partial characterization of a minienzyme form of the human matrix metalloproteinase-9 (MMP-9). The MMP-9 minienzyme gene construct consisting of the pre, pro, and catalytic domains of the MMP-9 was introduced into Sf9 insect cells using a baculovirus expression system. The expression of the recombinant MMP-9 minienzyme was estimated to be approximately 0.8 mg/L of cell medium. The recombinant protein was purified using a single-step gelatin-Sepharose affinity column and yielded a highly stable and active minienzyme with gelatinolytic activity. Moreover, two interesting findings related to MMP-9 interactions with heparin and TIMP-1 resulted from our studies. First, the pro and catalytic domains of the human MMP-9 are not sufficient for heparin affinity. Second, in contrast to the prevailing consensus, TIMP-1 blockade of the enzymatic activity of MMP-9 does not require prior binding to the C-terminus of its MMP-9 protein substrate.

Animals↗

Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat.

BACKGROUND AND PURPOSE: Acute cerebral ischemia after subarachnoid hemorrhage (SAH) is a major cause of morbidity whose precise etiology is unclear. The purpose of this study was to examine the relationships between cerebral perfusion pressure (CPP) and cortical blood flow during SAH using a new experimental model in the rat. METHODS: CPP (mean arterial pressure minus intracranial pressure), cortical laser-Doppler flowmetry (LDF), and electroencephalogram were continuously recorded during and after SAH in 16 ventilated rats. SAH was produced by advancing an intraluminal suture from the external carotid artery through the internal carotid artery to perforate the vessel near its intracranial bifurcation. RESULTS: Eight rats (50%) died within 24 hours of SAH. In all rats, blood was widely distributed throughout the basal, convexity, and interhemispheric subarachnoid spaces and throughout the ventricular system. CPP decreased after SAH at an initial rate of 1.1 +/- 0.2 mm Hg/s, reaching its nadir 59 +/- 9 seconds after the onset of SAH. During the same period, LDF fell at a rate of 1.4 +/- 0.3%/s (P = NS vs CPP). After reaching its nadir, CPP rose at a rate of 0.4 +/- 0.01 mm Hg/s, but LDF continued to fall at 0.2 +/- 0.03%/s (P < .05 vs CPP) reaching a nadir of 21.7 +/- 2.5% significantly later than CPP (189.5 +/- 39 s after SAH, P < .05). No correlation was found between peak changes in CPP and LDF. Electroencephalogram activity followed the changes in LDF, reaching nadir values 289 +/- 55 seconds after SAH. CONCLUSIONS: These findings demonstrate that although reduced CPP causes the initial decrease in cortical blood flow after SAH, secondary reductions occurring after CPP has reached its nadir are caused by other factors such as acute vasoconstriction. This noncraniotomy model of SAH in the rat has several advantages over existing models.

Animals↗

Pharmacologic-guided trial of sequential methotrexate and thioguanine in children with advanced malignancies.

PURPOSE: Based on in vitro studies that have shown synergistic effects of sequential administration of methotrexate (MTX) and thioguanine (6-TG), we conducted a pharmacologically guided trial of sequential MTX and 6-TG to determine the following: (1) the maximum-tolerated dose (MTD) of 6-TG; (2) the nature of the dose-limiting toxicity; and (3) the modulation effect of MTX on 6-TG given by this sequence and schedule. PATIENTS AND METHODS: Thirty-one children with advanced malignancies (acute leukemia, n = 10; lymphoma n = 10; and solid tumors, n = 11) were treated weekly for 3 weeks with a 2-week rest; treatment consisted of a fixed dose of MTX (30 mg/m2 over 24 hours) followed by a 2-hour infusion of 6-TG in escalating doses. RESULTS: Measurement of plasma MTX, 6-TG, and mononuclear 5-phosphoribosyl-1-pyrophosphate (PRPP) levels indicates that the desired biochemical modulation and serum levels were achieved. Nonhematologic toxicities were mild and the dose-limiting toxicity was bone marrow depression. A 300-mg/m2 dose of 6-TG with MTX is considered the MTD. Responses were noted in patients with lymphoma. CONCLUSION: Encouraging antitumor effects were produced with this regimen in heavily pretreated patients with lymphoma, particularly Hodgkin's disease (HD). The durations of responses were 17, 13+, 12, 9, and 7+ months. A phase II trial of the MTX/6-TG combination is warranted for the treatment of relapsed lymphoma.

Adolescent↗

[Coronary transluminal angioplasty using 6-french diagnostic catheters. A preliminary study].

This preliminary study was undertaken to assess the potential indication and limitations of the use of 6 French guiding catheters for percutaneous transluminal coronary angioplasty (PTCA). Between September 1992 and October 1993, 100 consecutive patients with an average age of 64 +/- 11 years underwent 6 F angioplasty for: stable angina (38.7%), unstable angina (32.4%), non Q-wave or infarction recanalized by thrombolytic therapy (18%), and acute myocardial infarction (10.8%). Eighty per cent of the pTCAs were performed immediately after diagnostic coronary angiography. Single vessel disease accounted for 93.7% of cases. Of the 118 lesions treated, 46.6% were types A or B1, 44.9% were type B2 and 8.4% were type C. The success rate of 6 F PTCA was 96.4% using an average of 1.08 guides and 1.25 balloon catheters per patient. Stenosis decreased from 83 +/- 10% to 26 +/- 16%. There were 4 technical failures: in 1 case it was not possible to pass a chronic occlusion, in 1 case coronary dissection was complicated by infarction, and in 2 cases a 7 F guiding catheter was required for successful PTCA. No patients required emergency coronary bypass surgery and there were no fatalities during the procedure. Four patients required perfusing balloon catheters and 8 were stented with a Palmaz-Schatz endoprosthesis with the 6 F catheter. These results are comparable to those obtained with larger diameter guiding catheters. In view of the good coronary ostial tolerance, the lower rate of local complications at the site of arterial puncture and the possibility of earlier mobilisation of patients after the procedure, the indications for 6 F PTCA should increase.

Adult↗

Nucleotide sequence of a transactivating Bombyx mori nuclear polyhedrosis virus immediate early gene.

The open reading frame (ORF) of 1572 bp contained in the 3.8 kb ClaI fragment of BmNPV encodes a viral regulatory protein which transactivates the delayed early AcMNPV 39K gene. Transactivation is induced in uninfected cells following transfection with a plasmid containing only the ClaI fragment. Hitherto immediate early gene promoter activity of the included 631 bp leader sequence is evident since no other viral elements are needed for the transcription of the regulatory gene.

Animals↗

Reciprocal ST segment changes in acute inferior myocardial infarction: clinical, haemodynamic and angiographic implications.

Reciprocal ST segment changes are frequent during acute inferior myocardial infarction, yet their significance remains controversial. In order to investigate the implications of these changes, the ECG obtained on admission for 83 patients with acute inferior myocardial infarction was compared with the clinical course and the results of angiographic and coronary arteriographic studies performed an average of 3 weeks after the onset of symptoms. Group 1 consisted of 59 patients with at least 1 mm of horizontal on downsloping ST segment depression in at least 1 of leads V1 to V4. Groups 2 consisted of 24 patients without precordial ST depression in this area. Group 1 patients were generally older than group 2 patients (59.6 +/- 6.4 versus 54 +/- 5.3 yr, P less than 0.01) had higher total creatine kinase (CK) levels and MB fractions (1835 +/- 940 versus 875 +/- 305, P less than 0.01, 269 +/- 102 versus 95 +/- 35 for MB fraction) and more complications during the hospital course (80% versus 38% P less than 0.01) and greater left ventricular dysfunction (ejection fraction 52.2 +/- 6% for group 1 versus 59.2 +/- 7% for group 2; cardiac index 2.75 +/- 0.41 min-1 m-2 for group 1 versus 3.25 +/- 0.31 min-1 m-2 for group 2 P less than 0.005). No difference was observed on biplane angiography as far as left ventricular wall kinesis was concerned.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

[Immediate coronary angioplasty in the acute phase of myocardial infarction. French multicenter study: December 1983].

Following the introduction of intracoronary thrombolysis in the acute phase of myocardial infarction (AMI), transcutaneous coronary angioplasty (TCA) was originally conceived as a logical complementary procedure to treat residual stenosis and so prevent the frequent post-thrombolysis reocclusion (20-30 p. 100 of cases). With increasing experience TCA of first intent appeared rational, more rapid and effective, ensuring coronary recanalisation (CR), suppression of residual stenosis and the prevention of reocclusion in the same procedure with with the objective of reducing the number of coronary bypass grafts (CBG) in patients with single vessel disease. A French multicentre study of 22 cases was organised by 9 centres. The average period between onset of symptoms and intervention was 2 hours 10 mins (range 30 mins-5 hours 30 mins). The average duration of the procedure was only 30 mins. 16 patients had anterior and 6 patients inferior AMI. Coronary angiography showed 12 occlusions (54.5 p. 100) and 10 sub-occlusions with 6 cases of delayed opacification. All patients had successful initial TCA with no major complications. The arterial occlusions decreased from 100 p. 100 to 31 p. 100 and the subocclusions from 94 to 12 p. 100. 2 patients died in the hospital period, one at the 48th hour of controlateral AMI and the other one at the 5th day of reocclusion. Three patients developed reocclusion at the site of the original TCA. Complete regression of ECG changes was observed in 31.8 p. 100 of cases. Complete recovery of normal left ventricular function was observed in 8 of the 17 patients who underwent follow-up investigations (47 p. 100 of cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A method of processing information on cineangiography of the right ventricle].

This paper describes our experience in making a programme for computer processing of biplane right ventricular cineangiography for the measurement of volumes and analysis of wall motion. The volumes were determined by a method of integration to the geometric model of a triangular pyramid i.e. trunco-pyramidal (IM.TP). The classical ellipsoidal integration method i.e. trunco-conal (IM.TC) and biplane and monoplane planimetry based on the model of a triangular pyramid (PM.TP) were used as references. Nineteen post-mortem RV casts were used to validate the programme. The correlations between the true volumes and the angiographic measurements were excellent (r = greater than 0.99) with both methods of integration, very good (r = 0.99) using the biplane PM.TP and very satisfactory (r = 0.91) with the monoplane PM.TP. The line of regression was very close to unity with the IM.TP and 0.9 with the PM.TP; this indicates the excellent adaptation of the triangular pyramid model to the shape of the RV. The IM.TP was used in a group of 20 right ventriculographies of patients without cardiac disease: the following results were obtained: EDV = 70.3 +/- 6.6 cm3/m2; ESV = 31.7 +/- 3.9 m3/m2; systolic index = 38.6 +/- 4.5 cm3/m2; ejection fraction = 0.55 +/- 0.04. The correlation of the values of systolic index by cineangiography and thermodilution (39.9 +/- 5.7 cm3/m2) was good (r = 0.86; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗

[Significance of ST segment depression in the precordial leads during the acute phase of inferior myocardial infarction].

Reciprocal changes of the ST segment in the acute phase of inferior myocardial infarction are common but their significance remain controversial. We studied this problem by comparing the ECG on admission of 83 patients with acute inferior myocardial infarction, with the clinical outcome and haemodynamic and angiographic data obtained on average 3 weeks after the onset of symptoms. Fifty nine patients (Group I) had ST depression greater than or equal to 1 mm in at least one of the leads V1 to V4; 24 patients (Group II) had no ST depression in this territory. The patients in Group I were older (59.6 +/- 6.4 vs 54 +/- 5.3 years, p less than 0.01), had higher total CPK (1 835 +/- 940 vs 875 +/- 305, p less than 0.01) and MB fractions (269 +/- 102 vs 95 +/- 35), more complications during the hospital period (80%, mainly haemodynamic vs 38%, p less than 0.01) and more severe left ventricular dysfunction: ejection fraction 52.2 +/- 6% vs 59.2 +/- 7%, p less than 0.05; cardiac index 2.75 +/- 0.4 l/min/m2 vs 3.25 +/- 0.3 l/min/m2, p less than 0.005). There was no difference in left ventricular wall motion between the groups on biplane angiography. However, coronary angiography showed left coronary disease to be more common in Group I (84%) than in Group II (37%), p less than 0.005. Left anterior descending and left circumflex disease was equally common. Patients with persistent ST depression after 48 hours had lower ejection fractions than those in whom it regressed within 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Intracoronary thrombolysis in myocardial infarction].

In more than 70% of the cases thrombi in the coronary arteries responsible for myocardial infarction can be dissolved by intracoronary injection of a fibrinolytic agent. For the left ventricular function to improve thrombolysis must be performed within 4 hours of thrombus formation; when performed later, results are inconstant. The risks of arteriography and thrombolysis (mostly dysrhythmias and haemorrhage) are real but acceptable. The mortality rate is lower than with conventional treatment. Improvement in left ventricular global ejection fraction is more pronounced in cases with collateral circulation and when thrombolysis is performed at an early stage. Thrombosis recurs within a few days in 15-20% of the cases. This can be prevented by aorto-coronary bypass or transluminal dilation of the stenotic vessel with a balloon catheter, either of these being carried out very early in cases with tight stenosis or delayed when the stenosis is significant but not life-threatening. A multicentre trial should be set up to find out whether intracoronary thrombolysis improves long-term survival and prevents late complications. But even if this were true, it should still be demonstrated that the method is as effective and safe as intravenous thrombolysis.

Aged↗

Selective coronary arteriography by percutaneous transaxillary approach.

Coronary angiography by the percutaneous femoral approach is widely used. This technique is potentially dangerous or impossible in patients with advanced arterial disease of the lower limbs, whether or not surgically treated. In these cases, percutaneous left or right axillary approach is an alternative to brachial approach. In this article, we report our multicenter experience involving 120 patients. The left axillary artery was used in 94 cases (78%) and the right in 26 cases (22%). We used performed coronary catheters usually associated with the femoral approach. The left axillary artery was used preferentially since this avoids catheterization of the innominated trunk and allows easier catheterization of the coronary ostia and aortic ends of aorto-coronary bypass grafts. The routine use of a sheath (arterial introducer) avoided arterial compression during catheterization, prevented hemorrhagic suffusion when the catheters were exchanged, and reduced the risk of thrombosis or laceration of the axillary artery. There were no failures in the catheterization of the axillary artery and no complication was observed during or after the procedure. Axillary percutaneous technique appears to have the following advantages over the brachial arteriotomy: 1) Investigation time is equivalent to the time needed for the femoral percutaneous approach. 2) There is the possibility of lateral and simultaneous bi-plane angiograms. 3) Arterial puncture is preferable to arteriotomy. The axillary approach could also be used for percutaneous transluminal coronary angioplasty.

Adult↗

[Coronary angioplasty immediately after intracoronary thrombolysis during the acute phase of myocardial infarction].

Since the introduction of intracoronary thrombolysis in the acute phase of myocardial infarction, all workers have observed a high incidence of coronary reocclusion (about 20%) essentially in the first hours and days after coronary recanalisation (CR). This had led to some groups carrying out transluminal coronary angioplasty (TCA) at the same time as CR by thrombolysis in situ to treat significant residual postthrombolysis stenosis. This french multicentre study carried out in 5 centres concerned 9 men (average age: 46.1 years) with 5 anterior infarcts (total thrombosis of the LAD artery) and 4 inferior infarcts (total thrombosis of the right coronary artery-RCA). Intracoronary trinitrate was ineffective in relieving the occlusion in all cases. In 5 cases, the thrombolytic protocol was streptokinase (SK) 3 000 u/min for 60 minutes; in the other 4 cases, the plasminogen-urokinase (Pg-UK) protocol was used. Thrombolysis was successful in all 9 cases. The results of TCA performed at the same time were also good (8/9 successes; 4 LAD and 4 RCA) without any complications during the procedure. There was only one immediate post-TCA reocclusion on a LAD artery. In all cases the initial ECG appearances of infarction remained, CR only appearing to prevent extension of the necrosis. The successful results of CR + TCA were maintained in 6 out of 7 patients reinvestigated 2 days to 6 months (average 6 months) after the initial procedure: the only case of reocclusion occurred after 48 hours on a RCA. The overall procedure never exceeded 2 hours.

Adult↗

[Coronarography by percutaneous puncture of the axillary artery. Value in arteriopathies of the lower limbs].

Coronary angiography by a percutaneous femoral approach using the Judkins-Bourassa technique with special preformed catheters is widely used. This approach is potentially dangerous or impossible in patients with severe lower limb arteriosclerosis even after operation and so the investigation has to be done by Sones' technique (denudation of the humeral artery). There is, however, another upper limb approach which does not involve arterial denudation: percutaneous right or left axillary artery catheterisation. This paper reports the experience of a multicentre study of this method in 105 patients. This study is of interest as an arterial catheter introducer was used which, does not compress the artery, prevents bleeding when the catheter has to be changed and reduced the risk of thromboses or laceration of the axillary artery. 73 of the 105 patients had lower limb arteriosclerosis 5 had aortic aneurysms and 1 patient had a previous history of femoral artery embolism. There was a primary indication for this approach in 21 cases. The left axillary artery was used in 83 cases (79%) and the right axillary artery in 22 cases (21%). The coronary catheters were those usually used with the femoral approach. The left side was chosen preferentially as it avoided the brachiocephalic trunk and facilitated the catheterisation of the coronary ostia and of aorto-coronary bypass grafts. Selective catheterisation of the left coronary artery was achieved in 21 out of 22 cases (95%) and of the right coronary artery in all 22 cases (100%) by the right axillary route. Both left and right coronary arteries were selectively catheterised in all cases by the left axillary approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Hemodynamic study during 48 hours of delayed-release isosorbide dinitrate (repeated oral administration) in the acute phase of myocardial infarction complicated by left ventricular insufficiency].

The aim of this study was to evaluate the haemodynamic effects of slow release isosorbide dinitrate (IDN) 40 mg oral preparation over a 48 hour period in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (8 male, 6 female) were treated by repeat dose ISD (8 hourly) and the haemodynamic changes were recorded at 1 hr, 2 hrs, 6 hrs, 12 hrs, 24 hrs, and 48 hrs. After 48 hours treatment the heart rate was unchanged; mean arterial blood pressure fell from 109.5 +/- 5.6 mmHg to 93.5 +/- 6.2 mmHg (-15%) (p less than 0.01). Cardiac index rose from 2.4 +/- 0.57 1/min/m2 to 2.8 +/- 0.65 1/min/m2 (+16%) (NS); diastolic pulmonary artery pressure fell from 22.5 +/- 7.07 mmHg to 13.7 +/- 4.5 mmHg (-39%) (p less than 0.003); systolic pulmonary artery pressure fell from 40.5 +/- 12.2 mmHg to 28.6 +/- 11.6 mmHg (-30%) (NS). Systemic vascular resistance fell from 2 095.2 +/- 63 dynes/s/cm5 to 1 537 +/- 60 dynes/s/cm5 (-22.3%) (NS). Finally, total pulmonary resistance fell from 561.9 +/- 15 dynes/s/cm5 to 301.9 +/- 14.5 dynes/s/cm5 (-47%) (p less than 0.003). The most valuable effect was therefore the reduction in left ventricular filling pressures which was maximal after about 48 hours. Two groups of patients were identified according to the clinical outcome. The patients in Group I (11 cases) were improved by the fall in diastolic pulmonary artery pressure, the rise in cardiac index and the reduction of systemic valvular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Accentuation of myocardial ischemia during coronary recanalization in the acute phase of myocardial infarction].

Coronary recanalisation during the acute phase of myocardial infarction, especially by in situ infusion of thrombolytic agents, is accompanied in most cases by rapid regression of chest pain and a reduction in the degree of ST elevation. However, a multicentre retrospective study of 104 attempts at recanalisation, including 78 successful procedures, showed in 10 cases (12.8 p. 100), an apparently paradoxical accentuation of the chest pain with or without increased ST elevation, at the time of angiographically demonstrable recanalisation. This phenomenon may be interpreted as being the result of aggravation of the ischaemia of the border zone, the objective of therapy. Several pathogenic hypotheses, all with experimental proof, may be suggested to explain these observations (haemorrhagic infarction, non reperfusion, ischaemic contraction due to massive intracellular flow of calcium, etc.). It is usually associated with arrhythmias and may be considered to be a reliable sign of recanalisation. It may also explain certain cases of persistence of chest pain and ECG changes despite the demonstration of a permeable epicardial artery on initial coronary angiography.

Coronary Angiography↗

[Implantation of permanent cardiac pacing electrodes by the retropectoral transvenous approach. Results of a series of 152 cases].

When the cephalic vein is unsuitable for the introduction of pacing electrodes, the retropectoral veins near the external border of pectoralis major near its subclavian attachment, approached through the same incision, may provide a suitable alternative. It was not possible to catheterise the cephalic vein in 23,8% of 756 consecutive implantations of endocavitary pacing electrodes. The retropectoral veins were looked for in 172 cases and found and used in 159 cases (92,4%). This percentage of success increased to 97,6% in the latter 83 attempts. These veins are usually very distensible. No complications or accidents were recorded. The only disadvantage was the relatively long dissection time. The stability of the pacing electrodes with this approach was excellent as reoperation was only required in 3% of cases (2 displacements and 3 exit blocks or pericardial migrations). This approach is therefore practicable in the large majority of cases in which the cephalic vein cannot be used. The multiplicity of the retropectoral veins should allow the introduction of two electrodes if sequential atrioventricular pacing were to be chosen. In addition, this approach would be useful when an atrial pacing electrode is to be added to a preexisting ventricular pacing electrode and one hesitates to puncture the subclavian vein because of the risk of damaging the electrode already in place. When direct subclavian puncture is the technique of choice of the operator, the retropectoral veins may be used when the subclavian approach is contraindicated or impossible. In any case, denudation of the retropectoral veins leads to fewer incidents than when the latter approach is used.

Electrodes, Implanted↗