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Biomedical subjects

E Garcia

Publications and source records attributed to E Garcia.

At least 163 records · Page 9Linked to original sources

Reduction and elimination of systemic heparinization during cardiopulmonary bypass.

After extensive experimental evaluation, heparin-coated perfusion equipment was clinically evaluated with low or no systemic heparinization in three different groups of patients (n = 47). In group 1, resection of descending thoracic aortic aneurysms (n = 24) was performed with heparin-coated equipment used for left heart bypass (n = 12) or partial cardiopulmonary bypass (n = 12) for proximal unloading and distal protection (heparin 5000 IU, autotransfusion). All devices remained functional throughout the procedures and no systemic emboli were detected. The sole death (1 of 24, 4%) occurred in a patient with ruptured thoracoabdominal aortic aneurysm requiring operation in extremis. Paraparesis with spontaneous recovery occurred in one patient (1 of 24, 4%). In group 2, coronary artery revascularization randomized for low (activated clotting time greater than 180 seconds) versus full (activated clotting time greater than 480 seconds) systemic heparinization was prospectively analyzed in 22 patients. All patients recovered without sequelae, and no myocardial infarction was diagnosed. Low dose of heparin (8041 +/- 1270 IU versus 52,500 +/- 17,100 IU; p less than 0.0005) resulted in reduced protamine requirements (7875 +/- 1918 IU versus 31,400 +/- 14,000 IU; p less than 0.0005), reduced blood loss (831 +/- 373 ml versus 2345 +/- 1815 ml; p less than 0.01), reduced transfusion requirements of homologous blood products (281 +/- 415 ml versus 2731 +/- 2258 ml; p less than 0.001), and less patients transfused (5 of 12 versus 10 of 10; p less than 0.05). Lower D-dimer levels in the group perfused with low systemic heparinization (0.50 +/- 0.43 mg/L versus 1.08 +/- 0.59 mg/L; p less than 0.05) were attributed to the absence of cardiotomy suction in this group. In group 3, rewarming in accidental hypothermia by cardiopulmonary bypass was successfully performed without systemic heparinization in a patient with hypothermic cardiac arrest (23.3 degrees C) and intracranial trauma. We conclude that systemic heparinization for clinical cardiopulmonary bypass can be reduced and eliminated in selected patients if perfusion equipment with improved biocompatibility is used. Bypass-induced morbidity can be reduced.

Aged↗

Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen.

Human resting B lymphocytes enter a state of sustained proliferation when incubated with both mouse fibroblastic L cells stably expressing Fc gamma RII/CDw32 and anti-CD40 antibodies. We have explored the effects of 11 recombinant human cytokines (CKs) on induced cell proliferation and immunoglobulin (Ig) production. Interleukin 4 (IL-4) was the only CK able to enhance anti-CD40-induced B cell multiplication as measured by enumeration of viable cells, and interferon gamma (IFN-gamma) further stimulated this induced proliferation. IL-4 enhanced the production of IgM and IgG by B cells and induced them to produce IgE. Combinations of IL-4 and IL-2 resulted in the production of large amounts of IgM and IgA. Interestingly, IFN-gamma did not inhibit the production of IgE by cells stimulated with anti-CD40 and IL-4. None of the tested CK combinations resulted in the production of large quantities of IgG. Therefore, this new culture system represents a unique model to study isotype regulation in highly purified human B lymphocytes, in addition to allowing the generation of long-term factor-dependent human B cell lines.

Antibodies, Monoclonal↗

Long-term human B cell lines dependent on interleukin-4 and antibody to CD40.

CD40 is a 45- to 50-kilodalton transmembrane glycoprotein expressed on B lymphocytes, epithelial cells, and some carcinoma cell lines. Human resting B lymphocytes entered a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40. In combination with interleukin-4, factor-dependent long-term normal human B cell lines were generated that were consistently negative for Epstein-Barr viral infection. Thus, cross-linking of CD40 is likely to represent an important phenomenon in the clonal expansion of B cells.

Antibodies, Monoclonal↗

A new complement fixation test for the diagnosis of neurocysticercosis in cerebrospinal fluid.

As a modification of the classical complement fixation test, a new test for immunodiagnosis in cerebrospinal fluid (CSF) was developed. When the assay was used for the diagnosis of neurocysticercosis in 149 CSF samples from patients and 1036 from controls, results showed 93% concordance with positives and 97% with negatives when compared with the results obtained by ELISA; in addition, it was positive in 12 of 16 cases of neurocysticercosis in which negative results had been obtained by ELISA. The new complement fixation test is particularly useful in CSF because of the immunological peculiarities of the subarachnoid space, where local synthesis of oligoclonal antibodies is induced by infectious agents. Reagents used for the assay are easy to produce and preserve, and the test is inexpensive, reliable and easy to perform. As this test detects the immunobiological consequence of the antigen-antibody reaction, it can be used in conjunction with other assays, such as ELISA, that measure the reaction directly, thus increasing the diagnostic possibilities. It may also be used where financial or technical limitations hinder access to other immunodiagnostic tests.

Animals↗

Perfusion without systemic heparinization for rewarming in accidental hypothermia.

We report on a patient with accidental deep hypothermia (23.3 degrees C) and cardiorespiratory arrest resulting from severe craniocerebral injury. Systemic anticoagulation was contraindicated, and the decision was reached to rewarm the patient with cardiopulmonary bypass without systemic heparinization using heparin-coated perfusion equipment. The patient was successfully rewarmed, was weaned from cardiopulmonary bypass, and recovered.

Adolescent↗

Detection of antibodies to mycoplasmas in South American camelids.

Indirect haemagglutination tests on sera from 757 South American camelids (alpacas, llamas and vicunas) carried out in the Andean region of Peru, revealed evidence of exposure mainly to Mycoplasma mycoides subspecies mycoides LC. The incidence of detectable antibodies to this mycoplasma in 554 alpacas was 5.0 per cent and in 141 llamas 15.6 per cent. Antibody to Mycoplasma capricolum and the F38 biotype was detected in 0.9 per cent and 0.2 per cent of alpacas, respectively. In a group of 62 vicunas only one reactor to both M m mycoides LC and M capricolum was observed. No reactors to M mycoides subspecies capri or M agalactiae were observed in the flocks examined. Antibodies to mycoplasma were also detected in nine out of 10 goat flocks tested. The incidence of antibodies to M m mycoides LC was 13.8 per cent, 3.8 per cent for M capricolum and 1.8 per cent for the F38 biotype. In a group of 110 sheep, six reactors (5.5 per cent) to M m mycoides LC and one (0.9 per cent) to F38 were observed. The implications of these results are discussed in relation to the involvement of mycoplasmas in existing disease in camelids in Peru.

Animals↗

Immunogenetics of human American cutaneous leishmaniasis. Study of HLA haplotypes in 24 families from Venezuela.

Twenty-four families with one or multiple cases of localized cutaneous leishmaniasis (LCL) from an endemic region with the highest incidence of LCL in Venezuela were typed from HLA-ABC, DR, DQ antigens and complement factors. The parental HLA haplotypes segregated at random among healthy and affected siblings but in backcross families significantly higher frequencies of HLA-A28 (p = 0.0018), -Bw22 (p = 0.0122), or -DQw8 (p = 0.0364) were present in affected compared to healthy siblings. HLA-B15 showed a higher frequency (p = 0.0062) among the latter group. Haplotypes Bw22CF31 (p = 0.0076) and Bw22DRw11DQw7 (p = 0.0163) were also significantly more frequent in affected compared to healthy siblings and A2Cw- (p = 0.0445) among the latter. No HLA genetic linkage with a putative LCL susceptibility gene(s) could be demonstrated in this study. A case/control comparison of 26 unrelated LCL patients (one proband from each family) and healthy individuals of the same ethnic origin confirmed the association of HLA-Bw22 (pc = 0.048) and -DQw3 (pc = 0.036) with LCL. The relative risk reached 12.5 for Bw22 and 4.25 for DQw3 with ethiologic factors of 0.17 and 0.64, respectively. HLA-DQw3 apparently makes the major contribution as a genetic risk factor for LCL at the population level.

Female↗

Technetium 99m sestamibi in the assessment of chronic coronary artery disease.

Extensive work has already been performed with regard to both planar and single photon emission computed (SPECT) technetium 99m sestamibi studies. Before widespread application of optimized acquisition and processing methods, clinical results between 99mTc sestamibi and thallium 201 were remarkably similar. It is anticipated that as techniques for 99mTc sestamibi planar and SPECT imaging become optimized, improvements in sensitivity and specificity for detection of coronary artery disease, over those observed with 201TI, might be forthcoming. This expectation is based on the improved image quality inherent in the use of the 99mTc agent with its higher count rate and higher energy. This improvement in image quality may be a principal reason for laboratories to switch from 201TI to 99mTc sestamibi imaging. It is anticipated that, with improved imaging characteristics, it will be easier for the average community hospital to obtain higher quality planar or SPECT imaging using 99mTc sestamibi rather than 201TI. In addition to improved image quality, the characteristics of 99mTc sestamibi allow gated planar or SPECT perfusion images to be obtained. It has been suggested that stress-gated SPECT sestamibi studies may provide all the information contained in a stress-rest nongated 99mTc sestamibi study, thereby potentially increasing patient throughput, a major concern with SPECT. Throughput can also be increased by using dual-isotope approaches with rest 201TI and stress technetium sestamibi acquisitions, employing either separate or simultaneous imaging with which the entire study can be accomplished in less than 2 hours. With simultaneous dual-isotope acquisition, camera time can be reduced by 50%. Finally, 99mTc sestamibi offers the advantage of the ability to perform first-pass exercise ventricular function and SPECT myocardial perfusion studies with a single injection of tracer. Regarding the assessment of myocardial viability, results to date suggest a very high degree of concordance between 201TI and 99mTc sestamibi studies using either planar or SPECT acquisition techniques. Correlative rest studies with both tracers will be of particular interest, as will preoperative and postoperative and position emission tomography correlation studies.

Aged↗

The product of the nitrogen fixation regulatory gene nfrX of Azotobacter vinelandii is functionally and structurally homologous to the uridylyltransferase encoded by glnD in enteric bacteria.

We sequenced the nitrogen fixation regulatory gene nfrX from Azotobacter vinelandii, mutations in which cause a Nif- phenotype, and found that it encodes a 105-kDa protein (NfrX), the N terminus of which is highly homologous to that of the uridylyltransferase-uridylyl-removing enzyme encoded by glnD in Escherichia coli. In vivo complementation experiments demonstrate that the glnD and nfrX products are functionally interchangeable. A vinelandii nfrX thus appears to encode a uridylyltransferase-uridylyl-removing enzyme, and in this paper we report the first sequence of such a protein. The Nif- phenotype of nfrX mutants can be suppressed by a second mutation in a recently identified nifL-like gene immediately upstream of nifA in A. vinelandii. NifL mediates nif regulation in response to the N status in A. vinelandii, presumably by inhibiting NifA activator function as occurs in Klebsiella pneumoniae; thus, one role of NfrX is to modify, either directly or indirectly, the activity of the nifL product.

Adenine↗

Clinical application of heparin-coated perfusion equipment with special emphasis on patients refusing homologous transfusions.

Clinical application of heparin-coated cardiopulmonary bypass equipment during perfusion with low systemic heparinization is reported with special emphasis on patients refusing any transfusion of homologous blood or blood products. Using the described technique, coronary artery revascularization was successfully performed in three Jehovah's witnesses. During perfusion, the activated clotting time (ACT) was maintained above 180 seconds. Prebypass haematocrit was 38 +/- 3% and dropped to 22 +/- 1% after seven days. Hence, cardiopulmonary bypass with low systemic heparinization may further reduce bypass induced morbidity and improve the final outcome in selected patients.

Aged↗

[Reduction of postoperative blood loss and donor blood use in heart surgery with aprotinin: experience with various dosages].

The effect of high dose aprotinin was evaluated in a prospective study on 100 patients undergoing cardiopulmonary bypass. Special attention was made on postoperative blood loss and transfusions of bank blood postoperatively. In the first part of the study, after induction of anesthesia, a loading dose of 2,000,000 kallikrein-inhibiting-unit (KIU) = 280 mg aprotinin was given intravenously over a 30-min period. Immediately afterward, a continuous infusion of 500,000 KIU/h was started and maintained until skin closure. Another 2,000,000 KIU was added to the priming volume of the heart-lung machine. A control group of 50 patients was randomized with similar indication for surgery and past cardiac history. The total loss from the thoracic drains was significantly reduced in the aprotinin group as compared with the loss in the control group (490 +/- 265 ml versus 1045 +/- 380 ml). In a separate group of risk patients (redo-operations, infective endocarditis) the total blood loss was even more significant reduced in the aprotinin group (690 +/- 195 ml versus 1585 +/- 290 ml). Patients of the aprotinin group received markedly less bank blood postoperatively (350 +/- 100 ml versus 900 +/- 240 ml without aprotinin). Part II of the study (36 patients) consisted of lower dosage (2,000,000 KIU intravenously during induction of anesthesia only or 2,000,000 KIU in the priming volume of the heart-lung machine only). Patients who received aprotinin in the heart-lung machine only showed no significant difference regarding blood loss and blood requirement to patients with high dose aprotinin. It appears possible that aprotinin reduces the activation of the coagulation during cardiopulmonary bypass and preserves platelet function without affecting platelet consumption during the extracorporeal circulation. The results of our study demonstrate that high dose aprotinin markedly reduces blood loss as well as homologous blood requirement in the early postoperative course of cardiosurgical patients. Similar effects due to reduced aprotinin dose have been observed in patients receiving aprotinin in the extracorporeal circulation only.

Aged↗

Reduced blood loss and transfusion requirements with low systemic heparinization: preliminary clinical results in coronary artery revascularization.

In coronary artery revascularization, low systemic heparinization was compared to full systemic heparinization during perfusion with heparin surface-coated cardiopulmonary bypass equipment. Twelve patients were randomly assigned to two groups and perfused with low [activated clotting time (ACT) greater than 180 s] or full (ACT greater than 480 s) systemic heparinization. A standard battery of blood samples was taken before the procedure, after heparinization, and at regular intervals during and after cardiopulmonary bypass. No differences were seen between the two groups in regard to age, body surface area, preoperative hematocrit, duration of bypass, bypass hypothermia, cross-clamp time, and number of bypasses per patient. However, there were more internal thoracic artery (ITA) grafts in the group with low systemic heparinization (1.5 +/- 0.8 ITA grafts per patient versus 0.8 +/- 0.4 ITA grafts per patient with full heparinization; p less than 0.05). The oxygenator gradient at the end of perfusion (before weaning) was 107 +/- 40 mmHg for low versus 110 +/- 10 mmHg for full heparinization (difference not significant). The total amount of heparin used was 7200 +/- 1030 IU for low versus 51400 +/- 9700 IU for full (p less than 0.05). Postoperative hematocrit was 35.0 +/- 2.0% for low versus 24.7 +/- 2.7% for full (p less than 0.05). Total chest tube drainage was 428 +/- 153 ml/m2 for low versus 935 +/- 414 ml/m2 for full (p less than 0.05). Homologous transfusions of blood products were necessary in 3/6 patients for low versus 6/6 patients for full (p less than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗

Performance characteristics of centrifugal pumps with heparin surface coating.

Heparin surface coating is one approach to improve the biocompatibility of existing blood pumps used for mechanical circulatory support. Experimental evaluation of centrifugal pumps with heparin surface coating was performed during open chest left heart bypass (3.7 L/min over 6 hours) in two series of bovine experiments. Eight calves (74 +/- 4 kg) were perfused either by heparin surface coated equipment without systemic heparinization or uncoated equipment with systemic heparinization (300 I. U,/kg bodyweight; ACT greater than 400 s). A standard battery of analyses was performed before and at regular intervals after onset of perfusion. At the end of perfusion all pump-heads were gently rinsed. There were no macroscopic clots for both groups whereas macroscopic clots were observed in uncoated tubings introduced for control in the group perfused without systemic heparinization. The hemodynamics were significantly better in the group perfused without systemic heparinization and maintained functional coagulation system. Clinical application of heparin surface coated equipment during resection of thoraco-abdominal aortic aneurysms is showing promising results in 12 patients.

Animals↗