Biomedical subjects
Publications and source records attributed to J Segovia.
Nine patients with systemic embolization complicating intracoronary stenting (incidence 1.8%) are described. Although this rare complication was not associated with any clinical sequelae, great care should be taken to prevent this possibility, especially in patients with unfavorable anatomic characteristics, including lesions in the left circumflex artery, at bend points, and calcified lesions.
A 75-year-old woman with severe rheumatic mitral stenosis was admitted for percutaneous mitral valvuloplasty. Two-dimensional echocardiography disclosed severe calcification of the posterolateral left atrial wall and interatrial septum. Percutaneous mitral valvuloplasty, using the inoue technique, was successfully performed after a transseptal puncture through the calcified interatrial septum, avoiding the need for surgical intervention.
A patient with rheumatic mitral stenosis associated with cor triatriatum is described. The anomalies were detected by two-dimensional echocardiography and confirmed by transesophageal echocardiography. Percutaneous mitral valvuloplasty was successfully performed with the inoue technique. The clinical and technical implications during the procedure of this previously unreported association are discussed.
A clonal cell line, AS583-8.E4.22, from the embryonic day 15 rat basal forebrain was established using retrovirus-mediated transduction of a temperature-sensitive mutant of the simian virus 40 (SV40) large tumour antigen. The cell line expresses cytoskeletal and neurotransmitter features indicative of neuronal commitment. In response to agents that increase intracellular cAMP, including forskolin and catecholamines, the cell line exhibits rapid process outgrowth and growth cone formation that does not require new gene expression or protein synthesis. The neurite outgrowth induced by catecholamines is mediated by beta 2-adrenergic receptors and is characterized by a rapid, reversible redistribution of filamentous actin. Neurons from primary cultures of embryonic day 15 basal forebrain were also found to respond to beta-adrenergic receptor agonists by enhancing growth cone formation. These results suggest that catecholamines provide cues that induce cytoskeletal rearrangements leading to neuronal process outgrowth and growth cone formation in the developing basal forebrain and possibly other neuronal progenitor cell populations. The neuronal basal forebrain cell line provides an ideal model to study the signalling mechanisms underlying the catecholamine-induced process outgrowth.
C6 is a cell line that expresses glial and neuronal markers. Treatments that increase intracellular cAMP levels induce the differentiation of these cells. We had previously demonstrated that forskolin, an agent that activates adenylate cyclase, produced changes in gene expression in C6 cells. As a consequence of this treatment, glutamic acid decarboxylase (GAD) activity and the mRNA for GAD67, one of the isoforms of the enzyme, decreased. In contrast, this treatment increased the transcription of the glial fibrillary acidic protein (GFAP) gene. We now show, by immunocytochemistry, that the changes in gene expression are phenotypically reflected by corresponding changes in the levels of the proteins encoded by the GAD67 and GFAP genes. Computer-assisted image analysis demonstrated that both the increase in GFAP immunofluorescence, and the decrease in GAD67 immunofluorescence are statistically significant. The changes in gene expression and in protein immunoreactivity are part of the differentiation process of the C6 cells towards a more mature glial phenotype.
Compared with pathologic studies coronary angiography is a relatively insensitive technique to detect early atherosclerosis. Coronary angioscopy is a new technique providing direct information on luminal vessel surface. To determine whether coronary angioscopy may detect the presence of atherosclerotic disease on angiographically normal coronary segments, 52 patients underwent a study with coronary angioscopy before coronary angioplasty. The mean age was 59 +/- 10 years; 46 patients were men and 6 were women. The reason for coronary angioplasty was unstable angina in 36 patients, stable angina in 8 patients, and silent ischemia in 8 patients. In seven patients angiography revealed luminal irregularities on the coronary segment proximal to the culprit lesion, and all these patients also had proximal disease as demonstrated by coronary angioscopy. In the remaining 45 (87%) patients angiography revealed a smooth-vessel contour proximal to the target lesion. On quantitative angiography these "normal" coronary segments measured 2.8 +/- 0.4 mm in luminal diameter. In 30 (67%) of these patients angioscopy revealed proximal disease on the vessel wall, but in 15 (33%) patients the luminal surface of these segments also appeared normal on angioscopy. Disease as detected by angioscopy in angiographically normal segments included yellow plaque in 19 patients, mural thrombus in 5, mixed plaques in 4, and small flaps in 2 patients. In eight patients coronary angioscopy detected that atherosclerotic disease extended proximally from the target lesion, but in the remaining 22 patients the angioscopic findings appeared to be discrete and well separated from the angiographic lesion. All these plaques were relatively small and did not protrude into the coronary lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: This study sought to elucidate angioscopic findings in totally occluded vessels before and after intervention. BACKGROUND: Coronary angioscopy allows direct visualization of the lumen surface of the coronary arteries; however, the utility of coronary angioscopy during coronary angioplasty of vessels with a total occlusion is unknown. METHODS: Twenty-one consecutive patients (mean [+/- SD] 58 +/- 9 years, range 39 to 77; 3 women, 18 men) undergoing dilation of an occluded vessel were studied with coronary angioscopy. Occlusions were classified as functional in 8 patients (Thrombolysis in Myocardial Infarction [TIMI] flow grade 1) and anatomic in 13 (TIMI flow grade 0). Once the guide wire had crossed the occlusion, coronary angioscopy was attempted before and after angioplasty. RESULTS: In all patients, coronary angioscopy before dilation visualized protruding material occluding the coronary lumen where the guide wire was wedged. The occlusion consisted of red thrombus in 19 patients (90%) (2 with isolated occlusive thrombus, 17 with thrombus associated with atherosclerotic plaque) and protruding yellow plaque in 2 patients (10%). However, on angiography only 7 occlusions (33%) had data consistent with thrombus (p < 0.01 vs. coronary angioscopy). Successful dilation was obtained in 20 patients. After dilation, coronary angioscopy was repeated in 18 patients, revealing residual thrombus with plaque in 16 (89%) and a residual yellow plaque in 2. In addition, coronary angioscopy revealed coronary dissections in 13 patients (72%); however, angiography revealed dissections only in 10 patients (55%) and residual thrombus in 2 (10%) (p < 0.001). In one patient, coronary angioscopy visualized silent distal embolization of a red thrombus not previously recognized on angiography. CONCLUSIONS: Before intervention, coronary angioscopy provides unique insights into the pathologic substrate of occluded coronary vessels. An occlusive plaque with thrombus is the most common underlying substrate in these lesions. After successful dilation, angiographically silent mural thrombus is seen in most patients. This information could be used to assist in the selection of candidates and type of coronary interventions and could also prove to be of prognostic value in patients with occluded vessels.
Four hundred and eighty six infected adults (90.7% men) were prospectively followed from 1988 to 1993 at a multiprofessional center in Santiago, Chile. 87.8% of male patients (pts)--84% of them homo/bisexual--and 64.4% of women acquired the infection sexually. At the beginning of the follow up (F/U) 51% of men and 71% of women were asymptomatic and 30% of the total group had AIDS. (AIDS definition: CDC 1993, excluded CD4 lymphocyte count < 200 x mm3). 240/486 (49.4%) had developed AIDS at the end of the study (12/31/93). AIDS defining events (ADE) were: interstitial pneumonia (confirmed or suggestive as caused by P. carinii [PCP]), 25%; tuberculosis (all forms), 22.1%; wasting, 13.8%; Kaposi Sarcoma, 9.2%; esophageal candidiasis, 6.7%; isosporiasis, 5.4%. Of all PCP cases, 72% were ADE, the rest, post.AIDS'. As expected, AIDS pts continued having major complications (mainly bacterial pneumonias, PCPs, esophagitis, tuberculosis and diarrhea due to I. belli and Cryptosporidium. Less frequently, but also observed, were toxoplasmic encephalitis and cryptococcal meningitis). Known mortality (excluded abandonment of F/U) was 27% for the whole group and varied from 5.8%, 51.6% to 69.2% for the first, 4th and 6th year of F/U respectively. For II-III CDC pts the mortality was 5% and 57% and for IV CDC pts it was 38% and 100% during the first and 6th year of F/U respectively. 36%, 53%, 74% and 85% of the pts followed for 1, 3, 5 and 6 years respectively had developed AIDS by the end of 1993. Multifactorial causes with either diarrhea, wasting or both were responsible for the death in half the pts in whom this was known, 15% died of respiratory complications and 5.7% of cryptococcal meningitis. 80% of AIDS pts survived their ADE. This study has provided information about the clinical profile of the HIV infection and natural history of the disease in Chile.
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BACKGROUND AND OBJECTIVE: Percutaneous coronary angioscopy (CAG) provides in vivo visual information about the luminal aspect of the vessel. In this report we describe our initial experience with CAG during coronary angioplasty (PTCA). METHODS: Fifty-five patients (age 60 +/- 9 years), 8 female, were included. Most patients, 42 (76%) were treated for unstable angina. RESULTS: In 49 patients (89%) CAG was performed prior to PTCA, and in all cases the intraluminal material responsible of the stenosis was recognized. This included plaque associated to thrombus in 29 patients (59%), isolated plaque in 15 (31%) and isolated thrombus in 5 (10%). Of these plaques, 25 (57%) were yellow, 14 (32%) were yellow and white and 5 (11%) were white. Of the 34 thrombi, 23 (68%) were mural and 11 (32%) protruding. CAG post-PTCA was performed in 43 patients (78%). CAG visualized residual plaque in 41 patients (95%) and residual thrombus in 34 (79%). In addition, CAG recognized dissections in 30 patients (70%). CAG was more sensitive than angiography for the detection of thrombus (pre-PTCA 34 [69%] vs 11 [22%]; p < 0.05, and post-PTCA 34 [79%] vs 5 [12%]; p < 0.05]) and coronary dissections (post-PTCA 30 [70%] vs 19 [44%]; p < 0.05). CAG before intervention caused angina in 39 patients (80%), ventricular fibrillation (successfully managed with DC cardioversion) in 1, and AV block in another patient. The angiographic result deteriorated in 4 patients (9%) immediately after the CAG performed following PTCA. A repeat balloon PTCA was required in these patients. CONCLUSIONS: CAG provides unique information on coronary lumen surface that complements angiographic data. As compared with angiography, CAG is more sensitive in the detection of intracoronary thrombi and dissections. Further studies are required to determine whether the additional information provided by CAG may be used, to select coronary interventions according to specific lesion characteristics, to optimize dilation results and, eventually, to improve the clinical outcome of these patients.
With the aim of assessing the effectiveness and safety of lovastatin in patients with hypercholesterolemia after heart transplantation, as well as the potential differences in the lipid-lowering effect of lovastatin between patients with or without pretransplant coronary artery disease (CAD), we studied 63 heart transplant patients who had serum total cholesterol > 250 mg/dl in spite of dietary therapy. Mean age of subjects was 47 +/- 2 years. Triple-drug immunosuppressive therapy consisted of cyclosporine, azathioprine, and steroids. Thirty-nine patients (62%) had pretransplant CAD and 24 (38%) did not. Pretreatment serum lipid levels were: total cholesterol, 302 +/- 32 mg/dl; low-density lipoprotein (LDL) cholesterol, 201 +/- 35 mg/dl; high-density lipoprotein (HDL) cholesterol, 60 +/- 19 mg/dl; triglycerides, 205 +/- 86 mg/dl; and total/HDL cholesterol ratio, 5.4 +/- 1.6. Patients received 10 to 40 mg/day of lovastatin (mean dose 17 +/- 6) for 13 +/- 4 months. There were no serious adverse events. At 3 months, lovastatin decreased total cholesterol by 15% (p < 0.001), LDL cholesterol by 21% (p < 0.001), triglycerides by 17% (p < 0.05), and total/HDL cholesterol ratio by 17% (p < 0.001), and increased HDL cholesterol by 3% (NS). Although lovastatin was effective in both patients with pretransplant CAD and non-CAD, analysis of its effect in each subgroup (CAD and non-CAD) revealed that its lipid-lowering effect was higher for non-CAD patients (-20% vs -12% for total cholesterol, and -27% vs -17% for LDL cholesterol, both p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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OBJECTIVES: The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease. BACKGROUND: Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance. METHODS: Twenty-seven patients (mean age [+/- SD] 57 +/- 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 different coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (delta A) and pressure (delta P) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [delta A/A]/delta P [mm Hg-1 x 10(3)]). RESULTS: Lumen area and plaque area were 12.6 +/- 5.7 and 3 +/- 3 min2, respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = -0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 +/- 2.1 vs. 1.8 +/- 1.2 mm Hg-1, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 +/- 1.9 vs. 1.6 +/- 1.1 mm Hg-1, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 +/- 0.7 vs. 2.3 +/- 1.6 mm Hg-1, p < 0.01) but was similar in concentric and eccentric plaques (1.6 +/- 1.5 vs. 1.6 +/- 0.9 mm Hg-1). Plaque area (r = -0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance. CONCLUSIONS: Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.
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Haloperidol, a dopamine receptor antagonist clinically used as an antipsychotic drug, induces long-term deleterious effects in offspring development when administered prenatally. However, the basis for this overall response to the drug remains unknown. Here we describe that prenatal administration of haloperidol in rats induces a drastic and selective reduction in the expression of plasticity-related genes in neonate forebrain, but not in mesencephalon. GABAergic and enkephalinergic markers such as glutamic acid decarboxylase activity and mRNA, and preproenkephalin mRNA were also diminished in forebrain. However, the expression of other genes such as epidermal growth factor-receptor, glial fibrillary acidic protein, and several proto-oncogenes (src, fos and myc), and a cholinergic marker such as choline acetyltransferase activity were unaltered. In addition, haloperidol promoted a significant decrease in mitotic cell number and cellular density in the striatum, one of the forebrain regions with the highest dopamine receptor density. These findings suggest that prenatal dopamine receptor occupancy may be a critical factor in controlling the development of forebrain target cells through mechanisms involving changes in the expression of plasticity-related genes.
OBJECTIVES: The aim of this study was to assess the implications of residual coronary dissections after stenting. BACKGROUND: Coronary stenting is currently used in selected patients with coronary dissection after angioplasty. However, in some patients the total length of the dissection may not be completely covered with the device. METHODS: Forty-two consecutive patients (mean [+/- SD] age 58 +/- 11 years; 39 men, 3 women) undergoing stenting for a major coronary dissection after angioplasty were studied. RESULTS: Thirty (67%) coronary dissections were small (< or = 15 mm), and 29 (64%) were occlusive (Thrombolysis in Myocardial Infarction [TIMI] flow grade < or = 2). In 3 patients, coronary stenting was unable to open large occlusive dissections, but a good angiographic result was obtained in 39 patients (93%). After stenting, 22 of these patients (56%) had no visible residual dissections, and 13 (33%) had small and 4 (10%) had large residual dissections. These residual dissections were stable and did not compromise coronary flow. In a repeat angiogram (24 h later) the stent was patent in all 39 patients. However, two patients experienced a subacute stent occlusion. Of the remaining 37 patients, 36 (97%) had a late angiogram after stenting. Quantitative angiography revealed a reduction in minimal lumen diameter at the stent site (2.6 +/- 0.4 vs. 2 +/- 0.7 mm, p < 0.05) and a trend toward improvement in vessel diameter at the site of the previous residual dissection (1.7 +/- 0.6 vs. 1.9 +/- 0.5 mm, p < 0.1). The angiographic image of residual dissection disappeared in all patients. These factors provided a rather smooth angiographic appearance at follow-up. The four patients with large residual dissections after stenting did not have restenosis and were asymptomatic at last visit. CONCLUSIONS: Coronary stenting is effective in the management of acute coronary dissections after angioplasty. In this setting, small residual dissections are frequently seen but have a good outcome and disappear at follow-up. Large residual dissections may have a good outcome if coronary flow is not impaired and no residual stenosis is visualized.
C6 cells express proteins and mRNAs that are characteristic of both glia and neurons. Agents that increase intracellular levels of cyclic AMP (cAMP) decrease the enzymatic activity of glutamate decarboxylase (GAD), a neuronal marker, and the mRNA levels for one of the two GAD isoenzymes, GAD67. This reduction is accompanied by increased levels of glial fibrillary acidic protein (GFAP) mRNA, an astrocyte marker. Transient transfection assays, in which a 2-kb upstream regulatory region of the human GFAP gene was linked to a reporter gene, indicate that at least some of the cAMP-mediated increase of GFAP mRNA levels is due to increased transcription. Increases in intracellular cAMP appear to induce differentiation of C6 cells toward a more mature astrocyte phenotype.
A patient with an excellent angiographic result after directional atherectomy suffered an acute coronary closure during an intravascular ultrasound study performed after the intervention. Intravascular ultrasound revealed a large medial dissection which could be successfully managed only with intracoronary stenting. The pathogenesis and implications of this rare major complication are discussed.