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Biomedical subjects

F Maddalena

Publications and source records attributed to F Maddalena.

At least 19 recordsLinked to original sources

Production of mouse monoclonal antibodies using a continuous cell culture fermenter and protein G affinity chromatography.

The production of anti-alpha-fetoprotein monoclonal antibodies for diagnostic use was carried out in a stirred tank fermenter equipped with a double membrane stirrer for bubble free aeration and continuous medium perfusion. A serum-free medium supplemented with 4 mM L-glutamine and 2.0 milligrams glucose with a protein content of only 780 micrograms/ml was used for the production process. The harvested antibodies were concentrated 50-fold using a tangential ultrafiltration system and were then purified in a one step purification process by protein G affinity chromatography. The purity of the final product (90%) was controlled by SDS-polyacrylamide gel electrophoresis, gel exclusion chromatography and isoelectric focussing. For further quality controls of the product the immunoglobulin subclass and the isoelectric point were determined and the specificity of the purified mAb was tested by RIA using 125I labelled alpha-fetoprotein. 1.87 g of purified monoclonal antibodies were produced (90% purity) within 2 weeks. It was found that the use of this type of stirred tank fermenter combined with a one step purification process using protein G affinity chromatography represents a suitable method for the fast production of medium scale quantities (500 mg-5 g) of monoclonal antibodies for diagnostic use.

Animals

[The efficacy and safety of slow-release nicardipine vs nifedipine in angina].

This controlled, double-blind, completely randomized study assessed the efficacy and safety of nicardipine and nifedipine, both in slow-release formulations, in patients with unstable angina. Thirty patients (28 M, 2F) were included in the final analysis, mean age 56.5 +/- 9.1 years (SD), mean weight 73.5 +/- 9.2 kg, mean height 171.5 +/- 6.5 cm, all with unstable angina. Nicardipine was given at a daily dosage of 80-120 mg, and nifedipine 40-60 mg, for up to one month. At the end of treatment with nicardipine supine systolic and diastolic blood pressure (SBP and DBP) dropped respectively 7.7% and 5.5% at 8 am and 8.6% and 7.1% at 8 pm. Nifedipine reduced SBP and DBP by respectively 6.5% and 13.1% at 8 am and 5.3% and 9.4% at 8 pm. There was no clinical or statistical difference between the treatments. Heart rate did not change appreciably during either treatment. On completion of nicardipine treatment, 87.5% of patients had suffered no angina attacks, compared with 66.7% for nifedipine. The remaining 12.5% of patients treated with nicardipine presented only one mild angina attack per day, while the other 33.3% of the nifedipine patients had one moderate angina attack per day. No untoward effects were reported with nicardipine; one patient receiving nifedipine presented cardiopalmus and another complained of headache. These results indicate that nicardipine is at least as safe and effective as nifedipine in the treatment of unstable angina.

Adult

Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes.

The present study was designed to investigate the capacity of human mononuclear phagocytes to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein (MCP), alternative acronyms JE, monocyte chemotactic and activating factor, MCP-1, and tumor-derived chemotactic factor). Human PBMC exposed in vitro to bacterial LPS expressed high levels of MCP transcripts. Monocyte-depleted lymphoid cells were not induced to express MCP by LPS. Percoll-gradient purified monocytes were able to express high levels of MCP transcripts. In an effort to exclude a role of contaminating non-monocytic cells, mononuclear phagocytes were separated by flow cytometry and sorting: CD14+ cells exposed to LPS showed high levels of MCP mRNA. LPS-stimulated monocytes released chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP antibodies. IL-1, TNF, IFN-gamma, granulocyte-macrophage-CSF and, to a lesser extent, macrophage-CSF, as well as inactivated streptococci, also induced MCP gene expression. Actinomycin D experiments indicated that induction of MCP in monocytes was gene transcription-dependent. The protein synthesis inhibitor cycloheximide (Cy) blocked IL-1-, TNF-, or LPS-induced MCP gene expression in monocytes. In contrast, expression of the structurally related chemotactic cytokine IL-8 was superinduced by Cy. Moreover, Cy superinduced MCP gene expression in cells other than monocytes, including endothelial cells, smooth muscle cell and fibrosarcoma cells, indicating different mechanisms of regulation in mononuclear phagocytes vs cells of other lineages. The capacity of cells of the monocyte-macrophage lineage to produce a cytokine that recruits and activates circulating monocytes may be of considerable importance in inflammatory and immunologic reactions. Thus, the mononuclear phagocyte system can autonomously regulate the extravasation and activation of immature elements of the same lineage, a key event in inflammation and immunity.

Antigens, CD

Interleukin 4 amplifies monocyte chemotactic protein and interleukin 6 production by endothelial cells.

Upon exposure to interleukin 4 (IL-4), human umbilical vein endothelial cells (EC) produced low amounts of IL-6 and expressed low levels of IL-6 transcripts. While being a weak stimulus for IL-6 production, IL-4 amplified the release and mRNA expression of this cytokine in response to optimal concentrations of IL-1. IL-4 also induced low levels of monocyte chemotactic protein but amplified the expression of this chemoattractant in response to inflammatory signals. Thus IL-4, by amplifying at the level of the vascular endothelium the expression of vascular cell adhesion molecule 1 selectively, as well as that of chemoattractants and IL-6, may favour the selective recruitment and activation of lymphoid and monocytic elements crucial for subacute/chronic inflammation and immune reactions.

Cell Adhesion Molecules

[Persistent T-wave inversion in unstable angina: the correlation with the global and regional function of the left ventricle].

The correlation between persistent negative T wave on basal electrocardiogram and coronary anatomy or global and regional left ventricular function was investigated in 34 patients with unstable angina defined as new onset (< 2 months), crescendo or rest angina. The patients with history of previous myocardial infarction, pathological Q waves on electrocardiogram or documented elevation of CPK were excluded. Eighteen patients (group A) showed T wave inversion (> 1 mV) in at least two leads on the basal electrocardiogram, persisting for at least 48 hours before coronary arteriography. In 16 patients (group B) the basal electrocardiogram was normal. Left ventricular volumes and ejection fraction were calculated and the regional systolic wall motion was analyzed using the area method in the 30 degrees right anterior oblique view. Hypokinesis was defined as more than 2 standard deviation below the mean value calculated in 24 normal subjects. No difference was present for age (A: 61 +/- 9 vs B: 57 +/- 9 yrs) and sex distribution. Critical stenoses of at least one coronary artery was documented in all but one patient (in group B). The number of critical stenosis per patient was equal (1.8) in the two groups. Left main coronary artery showed narrowing > 50% in three patients of group A and in two patients of group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Unexpected sudden death during acute myocardial infarction: role of primary electromechanical dissociation.

The causes of death during the acute phase of myocardial infarction were studied in 128 patients. Forty-three of these, who had no clear signs of cardiocirculatory failure, were considered to be cases of sudden and unexpected death. Thirty-two of these patients (74%) had electromechanical dissociation, defined as a sudden disappearance of an effective arterial pressure in the presence of adequate electrocardiographic complexes. Twenty-three patients who had been given this diagnosis were males and 9 females; 53% presented with anterior infarction, 31% with infero-posterior infarction, 3.5% with both anterior and infero-posterior and 12.5% with non-Q wave infarction. A previous episode of infarction was recorded in 31.2% of patients with electromechanical dissociation. Autopsy was performed in 84 patients, 23 of whom died with electromechanical dissociation. Half of the latter cases revealed cardiac rupture (secondary electromechanical dissociation), whereas in the other half death was due to primary electromechanical dissociation. The study stresses the relatively high incidence of this cause of death and the need to differentiate between the two different forms. Although at present the pathophysiology of primary electromechanical dissociation is not completely understood, we believe that recurrence of global or local ischemia may play a more important role than cardiovascular inhibitory reflexes.

Acute Disease

[Results of emergency aortocoronary bypass in complicated coronary angioplasty].

Sixteen out of 293 (5.4%) procedures for percutaneous transluminal coronary angioplasty, performed between 1985 and 1988, were complicated by acute closure and required emergency revascularization surgery. The injured vessel was the left anterior descending artery in 14 cases and the right coronary artery in 2 cases. All patients had persistent chest pain associated with ST-segment elevation in 14 cases and ST-segment depression in 2 cases. Two patients developed cardiogenic shock and were in cardiac arrest at the beginning of operation; one of these died immediately after the operation. Thus the overall mortality rate was 6.2%. Enzyme evidence of myocardial infarction (CPK-MB greater than 40 UI/I) occurred postoperatively in 8 patients (50%), but only the 6 patients (37.5%) with electrocardiographic evidence of myocardial necrosis (new Q-waves or loss of R-wave voltage) showed akinesis of the myocardium perfused by the occluded vessel at the echocardiographic examination performed two weeks after the operation. The occurrence of myocardial infarction was correlated with the degree of preoperative ischemia and hemodynamic deterioration. A collateral flow was present in 3 cases and none of these showed evidence of myocardial necrosis after the operation. Our results show that emergency bypass surgery for failed coronary angioplasty is less satisfactory than elective surgery, and has a higher mortality and myocardial infarction rate. Thus, the risk of emergency operation for complicated dilation must be considered when selecting of candidates for coronary angioplasty.

Adult

[Cardiac echinococcosis. Description of a case with cysts localized in the free wall of the left ventricle].

A case of isolated cardiac echinococcosis is reported. A 19-year-old man was hospitalized for chest pain with electrocardiographic pathological Q waves in D1, aVL, V5, V6. Two-dimensional echocardiography and chest computed tomography documented pericardial effusion and an intramyocardial cyst. Casoni's reaction and immunological tests completed the diagnosis of cardiac hydatidosis. The localization and the etiology of the cyst were confirmed during cardiac surgery.

Adult

[Coronary angioplasty in unstable angina. Immediate and short-term results].

We report the results of percutaneous transluminal coronary angioplasty (PTCA) in 67 consecutive patients with unstable angina. Twenty patients had new onset (less than 2 months) angina, 33 patients had crescendo angina and 14 had early postinfarction angina. Fifty-one patients had one-vessel disease, 12 patients had two-vessel disease and two patients had three-vessel disease; two patients had a stenosis of a venous graft. In cases with multivessel disease, we performed only the dilatation of the ischaemia-related vessel identified by morphologic features of coronary lesion and electrocardiographic changes during chest pain. The procedure was successful in 54 cases (80.6%). Seven patients (10.4%) had major complications. Emergency coronary artery bypass graft surgery was performed in 6 cases (8.9%) because of occlusion of the left anterior descending artery; despite emergency operation one patient died and two patients sustained a myocardial infarction. One patient had occlusion of the right coronary artery and inferior myocardial infarction. In all patients in whom angioplasty was successful unstable angina disappeared. At 6 months follow-up there were no infarctions or deaths but 14 of 42 patients (33%) had recurrent angina. Restenosis occurred in 16 of 33 patients (48%) who had repeat coronary angiography. Four patients with recurrence of unstable angina had repeat angioplasty; it was successful in 3 cases. One patient died of refractory cardiac arrest. The mortality rate of 71 procedures performed in 67 patients was 2.8% (2/71) and the overall myocardial infarction rate was 4.2% (3/71).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Atrial desynchronization induced by Valsalva's maneuver in a patient with reciprocating supraventricular tachycardia and Wolff-Parkinson-White syndrome].

A 22 years old man with ventricular preexcitation syndrome due to a left accessory pathway, was admitted because of orthodromic reciprocating tachycardia, 205 bpm in frequency. The patient was invited to perform a Valsalva Maneuvre, and at its ending, the tachycardia degenerated into atrial fibrillation (AF) associated with high ventricular rate, reverted to sinus rhythm by D.C. shock. The electrophysiologic study documented a left lateral by pass tract, with an anterograde refractory period of 230 msec. AF was inducible and had a minimal RR interval of 220 msec. Vagal stimulation, induced at the end of Valsalva maneuvre, probably caused dispersion of atrial refractorines and intraatrial reentry, converting the orthodromic tachycardia into atrial fibrillation.

Adult

[Vectorcardiographic analysis of late potentials].

We analyzed by high amplification vectorcardiography the morphology of the QRS ending loop and the ST segment of patients with previously recorded Lown 4A, 4B ventricular arrhythmias and the healthy subject. Eight patients were affected by ischemic heart disease and 7 by arrhythmogenic right ventricular dysplasia. All had some irregularities at the end of the QRS or in the ST segment, on the standard ECG. The VCG showed one or more of these three morphologies: complete or incomplete ring, rapidly inscripted isodi-triphasic potentials, sinusoidal irregularities. In the 20 healthy subjects, the loop corresponding to the last 30 msec of the QRS, till the end of the afferent portion of T, was regular, without any particular morphology. We think that these aspects could be related to delayed fragmentation of the ventricular depolarization.

Arrhythmias, Cardiac