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Biomedical subjects

A Sala

Publications and source records attributed to A Sala.

At least 127 records · Page 7Linked to original sources

[Heart surgery, cardiopulmonary bypass and inflammatory response. I. Changes in hemostasis and complement].

The use of cardiopulmonary bypass for surgical cardiac procedures is characterized by a whole-body inflammatory reaction due to the contact of blood through nonendothelialized surfaces; this stimulates the organism to recognize the cardiopulmonary bypass system as "nonself" and to activate specific (immune) and nonspecific (inflammatory) responses. These responses are then related with postoperative damage to many body systems, like pulmonary, renal or brain dysfunction, excessive bleeding and postoperative sepsis. In this paper, present knowledge on untoward responses of the patient to the use of cardiopulmonary bypass in cardiac surgery is reviewed and discussed, particularly focusing on the perturbation of the hemostasis and of the complement activation system.

Blood Coagulation↗

Myocardial revascularization procedures on multisegment diseased left anterior descending artery: endarterectomy or multiple sequential anastomoses (jumping)?

Complete revascularization is the primary goal in coronary surgery because of its superior long term results. However, in some patients the extent of the coronary artery disease is such that the usual coronary bypass technique may not allow to perform a complete myocardial surgical revascularization and, consequently, a satisfactory myocardial perfusion: so complementary revascularization techniques may become mandatory, especially when the diseased vessel is LAD or its branches. As a consequence, alternative procedures should be undertaken: coronary endarterectomy (EA) and multiple sequential anastomoses on a single vessel (jump), which guidelines are actually somehow controversial. Between January, 1989, and May, 1992, 53 patients underwent a myocardial revascularization procedure on LAD system unsuitable for single distal bypass; of them 35 (66%) underwent coronary endarterectomy, while in 18 (34%) multiple sequential anastomoses (jumping) were performed on the same vessel. About preoperative variables, average NYHA class (2.7 jump vs 2.1 EA group, p < 0.05), the history of more than 1 myocardial infarction (22.2% jump vs 2.9% EA, p < 0.04) and the presence of preoperative nitrates e.v (33.3% vs 8.6%, p < 0.04) were statistically higher in the jump group, suggesting a more unstable clinical status, while other clinical echocardiographic and catheterization features were not statistically different. For what operative and postoperative features are concerned, the number of anastomoses performed was statistically higher in the jump group, as exasperated (3.8 vs 2.7, p < 0.002) while perfusion (138 vs 141 min) and crossclamp time (103 vs 106 min) were similar. Furthermore we found a statistically lower incidence of perioperative myocardial infarction (0% jump is 22.8% EA group, p < 0.04); the postperfusion inotropic drugs requirement (22.2% vs 37.1%), the need of an intraaortic counterpulsation (0% vs 2.9%) and the in-hospital mortality (0% vs 5.7%) were lower in the jumping group too, also if they didn't reach statistical significance. Our experience suggest, also with the limits imposed by a retrospective case review and by a low number of cases reported, that myocardial revascularization of a multisegment diseased LAD system may be safely performed with the jumping technique with a low incidence of postoperative complications: it should be the first choice technique when conventional revascularization procedures are not enough to achieve complete myocardial revascularization. We advocate the use of EA technique only in that cases characterized by a diffuse atherosclerotic core and a well delimited plane of dissection, associated to a very poor runoff, which really excludes any chance to multiple anastomoses.

Aged↗

Inhibition of erythro-myeloid differentiation by constitutive expression of a DNA binding-deficient c-myb mutant: implication for c-myb function.

The c-myb proto-oncogene encodes a nuclear protein involved in the regulation of cell proliferation, differentiation, and development. Myb protein contains a DNA binding and a transactivating domain thought to mediate its biologic properties. The DNA binding domain consists of three repeats (R1, R2, and R3), each containing a highly conserved motif of tryptophan residues. A c-myb mutant (DR1-myb) lacking the last 46 amino acids of R1 and 23 amino terminal residues of R2, a region homologous to the ADA-2 yeast transcriptional adaptor, lost DNA binding ability, but remained able to transactivate the human heat-shock promoter. Transfection of murine 32D and murine erythroleukemia (MEL) cell lines with DR1-myb caused inhibition of cellular differentiation induced by granulocyte colony-stimulating factor (G-CSF) and dimethyl sulfoxide (DMSO), respectively. A second c-myb mutant (D-ADA2-myb) lacking the first 23 amino acids of R2, also lost DNA binding and transactivation activity, but did not inhibit DMSO-induced differentiation of MEL transfected cells. These findings suggest that deletion of R1 activates a DNA binding-independent mechanism of c-myb function, which may involve interaction of Myb with cellular factors.

Animals↗

Requirement of b-myb function for survival and differentiative potential of human neuroblastoma cells.

The B-myb gene belongs to a family of transcription factors that also includes A-myb and c-myb. B-myb is expressed in many cell types including human neuroblastoma cells. Here we demonstrate that B-myb expression is down-regulated during retinoic acid-induced neural and glial differentiation of neuroblastoma cells. This modulation is an early event, is maintained at late times of induction, and is in part regulated at the transcriptional level. Constitutive expression of B-myb prevents retinoic acid-induced neural differentiation as reflected by morphological features and the expression of (or lack of) biochemical markers associated with the undifferentiated phenotype. Furthermore, the expression of antisense B-myb transcripts does not allow the rescue of viable cells, suggesting an important role for B-myb in the survival of neuroblastoma cells. These results indicate that B-myb plays a functional role in the differentiative potential of neuroblastoma cells, raising the possibility that this gene is one of the nuclear regulators in the cascade of events leading to cellular differentiation.

Base Sequence↗

New antianginal nitro esters with reduced hypotensive activity. Synthesis and pharmacological evaluation of 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones.

New nitro ester 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones show marked inhibitory activity against ischemia-induced electrocardiographic changes, with only limited systemic hemodynamic effects, and are reported in the present study. These new nitro vasodilators are potent inhibitors of the electrocardiographic T-wave and S-T segment elevation induced by intravenous or intracoronary administration of Arg-vasopressin or methacholine in the anesthetized rat. The most active compounds are up to 300- and 600-fold more potent than glyceryl trinitrate or Nicorandil, respectively. These nitro esters relax in a concentration-dependent manner the isolated rabbit aorta, at higher concentrations (2-40-fold) than glyceryl trinitrate, and reduce the mean arterial blood pressure at doses 7-300-fold higher than those required by glyceryl trinitrate to exert a similar hypotensive effect. Remarkably, these compounds retain their anti-ischemic and hemodynamic profile after oral (po) administration. These new nitro ester derivatives, endowed with a marked antianginal activity, which is not associated with concurrent and pronounced falls in systemic blood pressure, represent the leads of a new class of selective nitrovasodilators having a preferential action on large coronary vessels, which could be clinically relevant in the treatment of coronary artery diseases.

Angina Pectoris↗

Mass disasters: rapid molecular screening of human remains by means of short tandem repeats typing.

Human remains identification represents a challenging situation and constitutes a difficult task associated with mass disasters. The only highly efficient means for individual and family group reconstruction is that based on DNA typing. On July 18, 1994 an explosion destroyed the A.M.I.A. (Argentine Israeli Association). Over 100 people died; however, the exact number of victims is still being investigated. Our Service received over 70 remains to be characterized by DNA typing in order to determine the number of victims and to try to reconstruct the family groups to which they belonged. DNA was extracted by a cetyltrimethylammonium bromide (CTAB) based protocol, a rapid molecular screening of all samples was carried out by multiplex STR amplifications including HUMTH01, HUMFABP, HUMHPRTB, HUMRENA4, HUMVWA, HUMFES/FPS and Y27H39LR. Samples with identical genotypes were HaeIII-digested. Southern blotted and probed with YNH-24 (D2S44). PH-30 (D4S139). LH-1 (D5S110) and MS-1 (D1S7) for variable number of tandem repeats (VNTR) evaluation. The minisatellite variant repeat (MVR) approach was used in those cases in which band or profile shift were detected in Southern blot assays. Kinship between victims and putative relatives was initially evaluated by comparison of short tandem repeat (STR) profiles and then confirmed by VNTR with the above probes. The high identification efficiency attained in this case is, in part, supported by a previous experience, the DNA-based molecular characterization of human remains caused by the explosion of the Israeli Embassy in Buenos Aires, March 1992.

Blotting, Southern↗

"Thinning-down phenomenon" and vasomotor adaptability of the inferior epigastric artery graft.

We report a case of diffuse thinning of an inferior epigastric artery early after its implantation as a coronary free graft. This phenomenon showed reversibility at the 20-month angiographic follow-up in response to progression of the proximal lesion in the recipient coronary artery. Graft vasodilation in response to atrial pacing and nitroglycerin infusion at late angiography confirmed the vasomotor adaptability of this arterial conduit.

Abdominal Muscles↗

Descending thoracic aorta aneurysmectomy: left-left centrifugal pump versus simple clamping technique.

Forty-six patients who had had an elective repair of a descending thoracic aortic aneurysm were reviewed, in order to investigate the efficacy of support by a centrifugal pump on distal organ perfusion and spinal cord protection during cross-clamping of the thoracic aorta. Two concurrent groups were analysed: 36 patients (78%) were supported by left atriofemoral arterial bypass with a centrifugal pump and 10 (22%) had no distal circulatory support. No patient was fully heparinized. The demographic data and preoperative characteristics of the groups, including location and type of aneurysm, were similar. The mean(s.d.) duration of cross-clamping was 37.8 (16) min in the centrifugal pump group and 42.3(21) min in the simple clamping group. Preoperative haemodynamic and laboratory data were similar in both groups. During cross-clamping, parameters of pH and blood urea varied but were better in the centrifugal pump group; changes from pre-intervention to early aortic cross-clamping time were not significant (pH, P < 0.0006; bases, P < 0.0003). Differences in creatinine values were caused mainly by the change from pre-intervention to the first postoperative day (P < 0.03); this continued throughout the hospital stay. The cerebrospinal fluid pressure measurement indicated a significant difference in time change (P < 0.0001) and mean level over time (P < 0.0002): levels were significantly lower in the centrifugal pump group throughout aortic cross-clamping. Three patients in the simple clamping group and none in the centrifugal pump group (P < 0.02) required cerebrospinal fluid drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Thoracic↗

The effect of "high dose" aprotinin and other factors on bleeding and revisions for bleeding in adult coronary and valve operations: an analysis of 2190 patients during a five-year period (1987-1991).

We retrospectively evaluated risk factors for postoperative bleeding and for revisions due to bleeding in 2190 adult coronary and valve patients who underwent surgery at our hospital during the 5-year period from 1987 to 1991. During this period 889 (40.6%) patients were given "high dose" aprotinin. Their mean age was 59.3 +/- 8.8 years, 1636 (74.7%) were males, 200 (9.1%) underwent surgery on an emergency basis and 72 patients (3.3%) underwent redo-operations. The patients were divided into four groups according to the type of surgery: all patients pooled together (2190), coronary artery surgery patients (1384, 63.2%, group I), valve surgery patients (706, 32.2%, group II) and combined (coronary plus valve) surgery patients (100, 4.6%, group III). Stepwise logistic regression analysis, performed to assess the risk factors for revisions due to bleeding showed aprotinin treatment to be the sole protective factor in all patients, group I and group II. In group III only the use of a hollow fiber membrane oxygenator proved a protective factor. Risk factors for revisions for bleeding were found to be aortic cross-clamp time in all patients, group I and group II. Use of the internal thoracic artery (ITA) was significant in group I patients and age at operation in group II. Multiple stepwise linear regression analysis, performed to evaluate the effect of various risk factors on cumulative postoperative blood loss in all patients, confirmed aprotinin as the only factor capable of reducing blood loss, while aortic cross-clamp time, coronary surgery and male gender showed a positive linear relation with postoperative bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

Composite valve graft replacement of the ascending aorta and the aortic valve by a modified button technique: the influence of aortic pathology on early mortality and late survival.

The risk factors for in-hospital mortality and mid-term survival in patients undergoing composite graft replacement of the aortic root with reimplant or coronary arteries by a modified button technique were evaluated with special emphasis on the underlying aortic pathology. Between 1985 and 1993 74 patients underwent replacement of the ascending aorta and the aortic valve following a modified button technique. The patients were divided into three groups according to aortic pathology: annuloaortic ectasia (43.58%), type A dissection (18.24%), and miscellaneous (13.18%). In-hospital mortality rates were 4.7%, 33.3% and 23.1%, respectively (P = 0.011). Univariate analysis showed that aortic pathology, NYHA class, emergency operation, redo operation, acute aortic dissection, preoperative cardiogenic shock, preoperative cardiac tamponade, longer cardiopulmonary bypass (CPB) and aortic cross-clamp times, and the need of femoral vein or femoral artery cannulation at intervention had univariate influence on in-hospital mortality. Multivariable stepwise logistic regression analysis identified CPB time odds ratio (OR) = 1.021/min, P = 0.007), the need of femoral vein cannulation at intervention (OR= 4.85, P = 0.008) and preoperative cardiac tamponade (OR = 3.11, P = 0.07) as independent predictors of in-hospital death. Follow-up ranged from 1 to 98 months (mean 39 +/- 30 months) with an actuarial survival rate of 75 +/- 9%, 52 +/- 13% and 67 +/- 14% at 5 years in annuloaortic ectasia, type A dissection, and miscellaneous patients, respectively (P = 0.18); when survival was evaluated in hospital survivors only, Kaplan-Meier survival rates were 77 +/- 9%, 79 +/- 14% and 89 +/- 10% at 5 years (P = 0.87). Comparing survival of annuloaortic ectasia patients (5-year survival 75 +/- 9%) versus survival of all other patients pooled together (5-year survival 55 +/- 11%), there was a statistically significant difference (P < 0.05); such a difference was no longer significant when comparing hospital survivors alone (5-year survival rate 77 +/- 9% annuloaortic ectasia patients vs 79 +/- 12% all other patients P = 0.61). Although aortic root replacement carries higher in-hospital mortality in some high-risk subgroups of patients, mid-term survival seems to be less affected by aortic pathology; high-risk patients are expected to have an out-hospital outcome comparable to the low-risk ones.

Aortic Dissection↗

Ectopic thyroid tissue in the ventricular outflow tract: embryologic implications.

The case of a 66-year-old female patient with a tumor located in the right ventricular outflow tract is reported. Histologic examination of an intraoperative biopsy revealed that the tumor was an intracardiac ectopic thyroid. We performed conservative surgery with partial resection of the mass. After 5 years, the patient is asymptomatic and leading a normal life. The authors examine the relation between the embryologic development of the primitive heart and the thyroid primordium and suggest the hypothesis of ectopic thyroid location in the right- or left-ventricular outflow tract.

Aged↗

Aortic arch surgery: pros and cons of selective cerebral perfusion. A multivariable analysis for cerebral injury during hypothermic circulatory arrest.

Thirty-five consecutive patients with aortic arch aneurysm who required surgical reconstruction were operated on with the aid of extracorporeal circulation between February 1985 and December 1993. Nineteen patients (54.3%) were treated with hypothermic circulatory arrest (HCA) (Group A) and 16 (45.7%) (Group B) with HCA and selective cerebral perfusion (SCP) through the carotid arteries. Preoperative characteristics didn't show any significant differences between the two groups: mean age was 58.7 +/- 12 vs 62.1 +/- 7, p = ns, male sex 73.6% vs 75%, p = ns; atherosclerotic aneurysms were 57.8% vs 43.7%, p = ns; Type A dissections 42.2% vs 56.3%, p = ns and emergency operation were 68.4% vs 43.7%, p = ns in Groups A and B respectively. For SCP, blood was infused initially at a rate of 200-300 ml/min, maintaining the 30-40% of cerebral blood flow in normothermia, successively, with the aid of transcranial Doppler sonography (TDS) SCP-flow was improved to 500-1000 ml/min. The MHz pulsed TDS was used to measure the middle cerebral artery flow velocity in deep hypothermia before the arrest, in order to adjust the SCP flow during the HCA. In all patients we used open aortic anastomosis; in two cases an extraanatomical ascending-descending aorta was required, and in other two the "elephant trunk" technique was used in case of combined aortic arch and descending aneurysms. The HCA times were similar in the two groups 47.5 +/- 22 vs 47.7 +/- 78, p = ns. Early deaths occurred in 5 patients of the Group A (26.3%) and in 3 patients of the group B (18.7%), p = ns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The discovery of a new organic nitrate: an overview.

Organic nitrates have been in therapeutic use for the treatment of angina pectoris for over a century. During the past decade, the search for new organic nitro esters with reduced side effects and improved oral bioavailability has been greatly intensified. We have discovered a new class of organic nitrates characterized by good oral activity and a coronary vascular selectivity greater than that of glyceryl trinitrate. Full structure-activity relationship studies of this new class of nitroesters are reported. From the screening of these compounds, ITF 296 was chosen for further evaluation.

Animals↗