[Embolic stroke by thrombotic non bacterial endocarditis in an Antiphospholipid Syndrome patient]. / Accidente cerebrovascular embólica por endocarditis trombótica no bacteriana en pacientes son Síndrome Antifosfolípido.

The antiphospholipid syndrome (APS) is an acquired thrombophilia, considered a systemic autoimmune disorder. We report a patient with APS who presented multiple cerebral infarcts (stroke) as a complication of a thrombotic non bacterial endocarditis. We review the literature focused on the physiological mechanism that produce this disease and its complications. Clinical features and their prognostic value and the different therapeutic options were also studied.

Kinking of carotid arteries is not a mechanism of cerebral ischemia: a functional evaluation by Doppler echography.

AIM: The aim of this paper was to evaluate the hemodynamic behavior of carotid kinking, as assessed by color Doppler ultrasonography at baseline and during neck movements, and their relation to neurological symptoms. METHODS: In this cross-sectional study, 60 consecutive patients with non-atheromatous carotid kinking in whom diagnostic color Doppler ultrasonography investigation of neck vessels had been requested for clinical suspicion of atherosclerotic disease were evaluated. To evaluate if there were significant changes of blood velocities as a consequence of kinking, for each carotid artery we recorded systolic and diastolic velocities both in the segments proximal to kinking, as well as intra-kinking. The effects of postural changes and neck movements on carotid blood flow were also studied. RESULTS: Flow in carotid arteries with kinking was always normal, and no differences were found between flow velocity measured at the level of kinking compared to the normal tract of the vessel. During head rotation tests, flow remained largely unaffected, a substantial reduction in the velocities in the ophthalmic artery was found in 13.5% of the cases, while an increase was recorded in 27%; and no symptoms or events were recorded during the study. None of the patients referred symptoms, nor were neurological events or signs detected during the maneuvers. CONCLUSION: Our results show that carotid kinks are not a mechanism of acute cerebral ischemia, and therefore are unlikely to be a cause of neurological events or symptoms.

Titanium compacts produced by the pulvimetallurgical hydride-dehydride method for biomedical applications.

Titanium powder production by the hydride-dehydride method has been developed as a non-expensive process. In this work, commercially pure grade two Ti specimens were hydrogenated. The hydrided material was milled in a planetary mill. The hydrided titanium powder was dehydrided and then sieved to obtain a particle size between 37 and 125 microm in order to compare it with a commercial powder produced by chemical reduction with a particle size lower than 150 microm. Cylindrical green compacts were obtained by uniaxial pressing of the powders at 343 MPa and sintering in vacuum. The powders and the density of sintered compacts were characterized, the oxygen content was measured and in vivo tests were performed in the tibia bones of Wistar rats in order to evaluate their biocompatibility. No differences were observed between the materials which were produced either with powders obtained by the hydride-dehydride method or with commercial powders produced by chemical reduction regarding modifications in compactation, sintering and biological behaviour.

Pig pancreatic islet transplantation into spontaneously diabetic dogs.

INTRODUCTION: Pig islet xenotransplantation represents an attractive way to solve our human organ shortage. In this preclinical protocol, we implanted adult porcine islets microencapsulated in alginate-polylysin into insulin-dependent diabetic dogs. METHODS: Pancreata were obtained from animals weighing 100 to 150 kg in a slaughterhouse. The islets were isolated by collagenase digestion. The encapsulation technique was a modification of Sun's method. Isolated islets (5000 islet equivalents per kilogram of dog weight) were mixed with 1.6% low-viscocity alginate. Microcapsules were cultured for 36 hours before implantation. The five dogs were in healthy prior to induction of diabetes mellitus at least 1 year prior. Under sedation, we implanted microcapsules. We performed determinations of peripheral blood insulin at baseline and every 3 months as well as glycosylated hemoglobin at baseline and every 4 months. During follow-up, glycemia was estimated twice a day at 3 hours after morning and night meals using a blood glucose monitoring system. RESULTS: We observed significant decrease (20%-80%) in insulin needs (P < .01). Of note, before the procedure no hormone was detected in the blood at 6 to 12 months after transplantation, plasma insulin had improved significantly (P < .05) and glycosylated hemoglobin also showed a significant decrease (P < .01). All owners subjectively claimed that their animals were enjoying a better quality of life. DISCUSSION: Our preliminary data suggested that pig islet microencapsulation achieved metabolic control in type I diabetic dogs without the risk of immunosuppression using one or two procedures per year.

Oxidative stress and mitochondrial damage in coronary artery bypass graft surgery: effects of antioxidant treatments.

We examined antioxidant actions in 73 patients undergoing coronary artery surgery by assessing mitochondrial damage and oxidative stress in ventricular biopsies obtained at preischemia and postreperfusion. Those patients who received antioxidant therapy benefited by less oxidative stress and mitochondrial damage.

Chromosomal alterations in atherosclerotic plaques.

Alterations of chromosomes 7 and 11 have been involved in the progression of atherosclerosis. Twenty-three carotid endarterectomy specimens were studied for the presence of alterations in chromosomes 7 and 11, and fibroblastic growth factor-3 (FGF-3) gene amplification. Besides classic histological stainings, immunophenotyping of cellular and vascular components and fluorescence in situ hybridization (FISH) were performed. At the caps, unstable plaques (n=18) showed inflammatory infiltration of macrophages, smooth muscle cells, and T-lymphocytes. Specifically in these regions, the FISH showed varying percentages of trisomy (15/18) and tetrasomy (8/15) of chromosome 7. In four cases polisomy 7 was noted in some nuclei. Monosomy of chromosome 11 and gene amplification of FGF-3 gene was observed. The FISH of the five stable plaques and normal arterial walls showed no chromosome alterations; furthermore, chromosome 3, which is not involved in atherosclerotic progression, presented a normal ploidy of smooth muscle cells in stable and unstable plaques and normal arterial walls. In conclusion, chromosome 7 and 11 alterations and FGF-3 gene amplification are components of unstable plaques, and might contribute to the evolution of stable plaques into complicated plaques.

Inflammatory cells, apoptosis and Chlamydia pneumoniae infection in atherosclerosis.

Chlamydia pneumoniae (CP), chromosomal alterations and apoptosis were suggested as contributing factors in the pathogenesis of atherosclerosis. Early (EP) and unstable plaques (UP) were studied in order to assess infiltrate composition, the apoptotic index, chromosome 7 stability and to investigate the concurrent presence of CP in EP and UP. Paraffin embedded sections of three iliac arteries and four aortas from young donors (EP), and four coronaries and nine carotid arteries (UP) were used. Aside from histological techniques, immunophenotypification for macrophages, T and B cells, smooth muscle and endothelial cells; FISH and DNA nick end labeling were performed. The amplifications with PCR for CP infection were negative in all specimens. In the EP, a focal myointimal thickening with foam cells and scarce smooth muscle cells was observed. Macrophages were most frequent in the intima (10.8%) while T and B cells were found in 2.3 and 1.5%. In the UP a thin cap covering a lipid-rich core with widespread vascularization and with severe luminal obstruction was observed. Macrophages were increased (21%), and T (1.5%) and B cells (3.5%) in the caps and inner areas of the lipid cores. At these sites, the FISH showed trisomy and tetrasomy of chromosome 7 and apoptosis was very frequent (10-30%). Macrophages in intimal lesions is one of the most prominent, consistent and permanent features in EP, and an elevated apoptotic index and chromosome 7 instability might contribute to evolution from stable to complicated plaques, while CP seems to play no role. However, further studies are needed with more cases to confirm this last observation.

[Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]. / Actividad proliferativa y alteraciones cromosómicas de las células musculares lisas en la ateroesclerosis.

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Actividad proliferativa y alteraciones cromosómicas de las células musculares lisas en la ateroesclerosis. / [Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved.

BACKGROUND: A complete immunohistochemical characterization in complicated carotid plaques is still lacking. The cellular components of 165 carotid endarterectomy specimens were analyzed to assess their role in the pathogenesis of plaque rupture and intraplaque hemorrhage without rupture. METHODS AND RESULTS: The fibrous caps at the sites of plaque rupture showed CD68+ macrophages, T-lymphocytes, and scarce B-lymphocytes. Ruptured plaques showed mononuclear infiltrates in the caps, shoulders, and bases of the plaques in 85% of the cases. Only 46% of nonruptured plaques showed such infiltrates (P <.0001). Two types of lipid cores were recognized: avascular or mildly vascularized and highly vascularized. The vessels of the latter type reacted with CD31 and CD34. In 57.5% of the cases, the base and the shoulders of the plaques showed neoformed, CD34+ vessels, often surrounded by mononuclear infiltrates. Intraplaque hemorrhage without rupture had highly vascularized lipid cores in all cases. T-lymphocytes and macrophages were in close contact with neoformed vessels. CONCLUSIONS: Plaque rupture is characterized by mononuclear cell infiltration of the caps, whereas intraplaque hemorrhage without rupture is characterized by extensive vascularization of the plaque.

Cardiac involvement in acquired immunodeficiency syndrome--a review to push action. The Committee for the Study of Cardiac Involvement in AIDS.

As more effective therapies have produced longer survival times for human immunodeficiency virus (HIV)-infected patients, new complications of late-stage HIV infection including HIV-related heart disease have emerged. Almost any agent that can cause disseminated infection in patients with acquired immunodeficiency syndrome (AIDS) may involve myocardium, but clinical evidence of cardiac disease is usually overshadowed by manifestations in other organs, primarily the brain and lungs. Cardiac abnormalities are found at autopsy in two-thirds of patients with AIDS, and more than 150 reports of cardiac complications have been published. Cardiac involvement in HIV disease includes pericardial effusion, myocarditis, dilated cardiomyopathy, and/or endocardial involvement at any stage of the disease. This review deals with all the cardiac manifestations of AIDS and serves to highlight two problems and one indication. First of all, there are very few clinical studies. Current knowledge is based almost exclusively on echocardiography and autopsy studies. Observational or clinical trials would be useful. Second, there exists very poor information on the impact of treatment; and epidemiologic and clinicopathologic studies are mandatory for obtaining detailed data concerning the mechanisms of myocardial damage in AIDS. Finally, because cardiac complications are often clinically inapparent or subtle in the initial stages, periodic screening of HIV-positive patients by electrocardiogram and echocardiogram is probably indicated. In addition, AIDS may also provide the opportunity to gain insights into the pathogenesis of little understood cardiac diseases such as lymphocytic myocarditis and dilated cardiomyopathy.

Mortality and morbidity from smoking-induced cardiovascular diseases: the necessity of the cardiologist's involvement and commitment.

This review deals with tobacco-associated cardiovascular effects and diseases. The importance of tabaccoism in primary care, its effects on cardiovascular, and immunology system and hemostasia, as well as, the role of smoking in atherosclerosis, coronary heart disease, acute myocardial infarct, diabetes, and other alterations are discussed. Finally we summarize the general tobacco control policies and the methods to achieve smoking cessation. Although it is well established the causal relationship between smoking and disease, and the general public is aware of this, the cardiologist's involvement and commitment is of utmost importance.

Pulsed electromagnetic fields in experimental cutaneous wound healing in rats.

Electromagnetic fields are now being used in many diseases such as osseous, ligamental, cartilaginous, or nervous reparation, diabetes, and myocardial or cerebral ischemia. Although many publications show the usefulness of magneto-therapy, discrepancies exist about the utility of electromagnetic fields in skin wound healing. The objective of this work was to study the effect of pulsed electromagnetic fields on wound healing in rats. Twenty-two male Wistar rats were used; a circular lesion was made in the back of each animal. They were divided into three groups: group C (control) with sham treatment (n = 8), group NF, treated with topical nitrofurazone solution (n = 7), and group PEMF, treated with pulsed electromagnetic fields of 20 mT (n = 7). The treatments were 35 minutes twice a day. The absolute and relative values of the area and perimeter of the wounds showed significantly lower values in the PEMF group at days 7, 14, and 21 compared with those in group C (p < 0.01, analysis of variance), whereas the PEMF group showed significantly lower values at day 21 only compared with the NF group (p < 0.01, analysis of variance). The results suggest a significant beneficial stimulation in the wound healing process in rats treated with PEMF, which could lead to the development of a practical tool for research and clinical use.

[Effect of magnetic fields on skin wound healing. Experimental study]. / Efecto de campos magnéticos sobre la cicatrización de la piel estudio experimental.

Although there are many publications on the usefulness of magneto-therapy, discrepancies exist about the utility of electromagnetic fields in skin wound healing. The objective of this work was to study the effect of electromagnetic fields on wound healing in rats. Thirty six male Wistar rats were used; a rectangular lesion was made in the back of each animal (4.2 cm x 2.3 cm). They were divided into 3 groups: group C (control) with sham treatment; group C50, treated with continuous electromagnetic fields of 5 mT (50 Gauss) and group P200, treated with pulsed electromagnetic fields of 20 mT (200 G). The treatments were of 30 minutes a day during 21 days. The corporal weights (Table 1) and the wound longitudinal and transversal maximal axis (Figures 1, 2) were weekly recorded and the data was evaluated by analysis of variance. On day 14, the P200 group showed the maximal longitudinal axis which was smaller than that of group C (p < 0.01). On day 21 in both treated groups the maximal longitudinal axis was smaller than that of group C (p < 0.01); besides the axis was smaller in the P200 group than in the C50 group (p < 0.05). No statistical differences were observed in the remaining data. The results showed a facilitating effect of electromagnetic fields on wound healing in rats. Pulsed electromagnetic fields seem to have a precocious and larger healing effect than continuous electromagnetic fields.

[Ischemia-reperfusion experimental model in the rabbit: ligation of the circumflex coronary artery versus ligation of the anterior descending coronary artery]. / Modelo experimental de isquemia-reperfusión en el conejo: ligadura de la arteria coronaria circunfleja versus ligadura de la arteria coronaria descendente anterior.

INTRODUCTION AND OBJECTIVES: The myocardial damage during ischemia and reperfusion in the rabbit was studied, in order to compare two different models: the occlusion of the circumflex coronary artery (Cx) vs the occlusion of the left anterior descending coronary artery (LAD). METHODS: Each group consisted of 10 New Zealand rabbits; after 50 minutes of occlusion the artery was reopened for 20 minutes and then a biopsy from the area at risk and another from the perfused area were obtained. The specimens were used for chemiluminiscence and electron microscopy. Electrocardiograms were taken throughout the experience. Transverse sections of both ventricles were used for light microscopy. RESULTS: In both groups elevations of the ST segment, more important in the Cx group (p < 0.001) were observed. In the LAD group, the QRS complexes were enlarged in three animals, in 4 rabbits there were reperfusion arrhythmias, but the experimental mortality was zero. In the other group, 50% of the animals died during the experiment. In the LAD group the chemiluminiscence of the area at risk was greater than that of the perfused area (p < 0.001). No differences could be demonstrated between the samples of the Cx group, probably because of the extensive necrotic areas unable to generate photoemission. Ultrastructural and microscopic characteristic lesions of the ischemia-reperfusion phenomena were found in both groups, particularly severe in the Cx group with extensive areas of necrotic tissue. CONCLUSIONS: This experience shows that the myocardial necrosis, the mortality and the malignant arrhythmias were quantitatively different according to which coronary artery was occluded. This fact may be taken into account when an animal model for ischemia-reperfusion is selected.

Beneficial effects of cloricromene in ischemic reperfused myocardium.

Cloricromene (Clo) has been used to prevent myocardial damage after transient occlusion of the circumflex coronary artery (Cx). Twenty rabbits were injected for 4 days with a single dose of Clo (0.25 mg/kg i.v.) or placebo. On the 5th day, the Cx was occluded, and Clo (6.4 micrograms/kg/min) or placebo was continuously infused. After 50 min, the occlusion was removed and after 20 min of reperfusion, the rabbits were sacrificed. In the placebo group, all rabbits showed marked ST segment changes and severe ischemic arrhythmias (6/10 animals). In 5 of them, ventricular fibrillation was followed by death. In the Clo group smaller ST segment elevations were observed, and in 2 rabbits ventricular fibrillation spontaneously reversed as did ST segment elevations. A significant reduction of the necrotic area was also observed in the Clo group by postmortem examination.

Immune response against Trypanosoma cruzi antigens in Cebus apella monkeys.

The american primate Cebus apella has been used as an experimental model for the study of acute and chronic Chagas' disease. The antibody response elicited by 4 x 10(6) blood trypnomastigotes injected into four monkeys was analysed. Peak titres of IgM and IgG of anti-Trypanosoma cruzi antibodies were found at day 22, and between days 20 and 40 post-infection (p.i.), respectively. The ability of a Mr 37kDa (T37K) glycoprotein purified from T. cruzi epimastigotes to generate IgG anti-T. cruzi antibodies in monkeys, and protect them against a challenge with trypomastigotes, was also studied. Monkeys non-immunized with T37K reached peak values of parasitaemia between days 18 and 21 post-infection, whereas immunized monkeys had lower parasitaemias without important variation. Anti-T37K antibodies in immunized monkeys decreased from day 2 with the lowest titres between days 14 to 22 p.i., coincident with the peak of parasitaemia in control non-immunized monkeys. These results suggest that anti-T37K antibodies could be responsible for the low parasitaemia detected in immunized monkeys.

Gastric acid secretion response in the Cebus apella. A monkey model of chronic Chagas' disease.

The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg) or pentagastrin (64 micrograms/kg) in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n = 10; Colombian, n = 4 and Tulahuen, n = 4) and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead) and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (p < 0.01 and p < 0.05 respectively; "t" test) in comparison to the controls. Barium contrast studies showed enlargement and dilatation of the colon in three infected animals. Histopathological lesions were seen in 75% of the autopsied animals either in colon alone (33%) or both, in colon and esophagus (42%). The normal secretion observed in the CA1 infected group could be due to a lower virulence of the strain, a lower esophageal tropism or the necessity of a longer post-infection time to cause lesions.