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Biomedical subjects

R Correa

Publications and source records attributed to R Correa.

At least 55 records · Page 3Linked to original sources

A model to assess interventions to improve collateral blood flow: continuous administration of agents into the left coronary artery in dogs.

OBJECTIVE: The aim was to develop an experimental model in which angiogenic growth factor(s) could be targeted locally to enhance myocardial collateral formation. A preparation was developed in which agents could be infused selectively into the left main coronary artery on a chronic basis to assess the potential of acidic fibroblast growth factor (FGF) to improve collateral blood flow. METHODS: Ameroid constrictors were placed on the left circumflex coronary artery of mixed hounds. Five weeks after ameroid placement, the artery was ligated and transected at the point of ameroid occlusion; a catheter was inserted and passed retrogradely into the left main coronary artery. The catheter was connected to an implantable infusion pump that provided continuous intracoronary drug infusion for 4 weeks. Dogs were randomised to receive acidic FGF with heparin (30 micrograms.h-1 and 30 IU.h-1, respectively, n = 16) or heparin alone (30 IU.h-1, n = 14). Regional myocardial blood flow was determined in the conscious state at the beginning and end of treatment. RESULTS: There were no deaths or important surgical complications related to the establishment of the coronary artery infusions. During the treatment interval (5-9 weeks after ameroid placement) the ratio of maximum ischaemic zone/normal zone blood flow increased from 0.39(SD 0.10) to 0.50(0.11) (p < 0.01) in dogs treated with acidic FGF plus heparin; however, similar improvement was noted in dogs treated with heparin alone. Ischaemic zone and normal zone vascular density was also equivalent in the two groups. CONCLUSIONS: This preparation makes possible the chronic intracoronary administration of agents which may promote myocardial angiogenesis, and allows assessment of collateral blood flow before and after treatment. As given in this investigation, acidic FGF had no demonstrable effect on collateral blood flow; however, this model may facilitate the identification of agents that do enhance myocardial collateral formation.

Animals↗

Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina. A clue to the mechanism of transformation from the stable to the unstable clinical state.

BACKGROUND: The mechanisms responsible for the transformation of stable angina to unstable angina, a major cause of morbidity and mortality, are commonly believed to be plaque rupture and thrombosis. We determined whether additional mechanisms are operative by analyzing the histopathology and immuno-histopathology of coronary plaques retrieved by directional atherectomy of patients with unstable angina in whom no intraluminal thrombus was demonstrated by angiography. METHODS AND RESULTS: The histological findings of atherectomy specimens from 34 patients with unstable angina were compared with those of 24 patients with postangioplasty restenosis, whose lesions are known to be composed of smooth muscle cells (SMCs), and 10 patients with stable angina, whose lesions contain relatively few SMCs. We also studied the expression of acidic and basic fibroblast growth factors (aFGF and bFGF), whose role in the vascular response to injury has been established. Specimens from unstable angina resembled those from postangioplasty restenosis in regard to SMC abundance (scale, 0 to 3; 1.4 +/- 0.9 versus 1.7 +/- 0.9; P = NS), and both differed from those of stable angina. Thrombus and/or hemorrhage occurred in only 34% of patients with unstable angina (compared with 8% of restenosis patients and in none of stable angina patients). Active lesions (defined as lesions (defined as lesions containing one or more of the following: thrombus, hemorrhage, abundant and disorganized SMCs in the presence of loose connective tissue, or inflammatory infiltrate) were observed in 56% of the unstable angina patients and in 50% of the restenosis patients but in none of the stable angina patients. The expression of aFGF and bFGF was detected in 80% to 100% of unstable angina (n = 11) and restenosis (n = 10) specimens but in only 1 of 5 stable angina specimens. CONCLUSIONS: Microscopic evidence of thrombosis and plaque rupture occurred in only one third of unstable angina patients, selected because they had no angiographic evidence of intracoronary thrombus. Moreover, their lesions resembled those of restenosis patients in regard to SMC abundance, lesion activity, and the expression of aFGF and bFGF. Our findings therefore suggest that an alternative mechanism to plaque rupture and thrombus formation may be operative in the precipitation of unstable angina; namely, in a subset of patients, SMC proliferation may lead to gradual plaque expansion and thereby to lumenal narrowing and unstable angina. Our data also suggest a role for aFGF and bFGF in this process.

Adult↗

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers.

BACKGROUND: Recently, laser-heated and radio frequency-heated balloon angioplasty techniques have been proposed as a means to treat or minimize dissection and elastic recoil but have been associated with a high rate of clinical restenosis. Similarly, pulsed laser angioplasty techniques proposed to minimize thermal injury while ablating obstructing atheroma have failed to reduce clinical restenosis. Because "hot balloon" and pulsed laser angioplasty create both mechanical and thermal injury, it has been difficult to discern the cause of the smooth muscle cell (SMC) proliferation resulting in restenosis and whether such magnitude of proliferation is predictable and dose related. This study was undertaken to explore these issues. METHODS AND RESULTS: Localized thermal lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser in nine rabbit aortas, which consistently led to a focal proliferation of SMC that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser irradiation at multiple independent sites of 24 central rabbit ear arteries without ablation led to brief approximately 30 degrees C thermal transients and thermal damage to the artery wall resulting in significant neointimal proliferation by 3 weeks and a mean cross-sectional narrowing of 59 +/- 17% at a dose of 390 mJ/mm2. Acute and chronic responses to varying total energy deposition were studied by histology after the rabbits were killed at 2 hours to 4 weeks. Arterial segments midway between laser injuries were unaffected and served as internal controls. Neointimal proliferation at 3 weeks after laser injury exhibited a clear dose dependence. Mean cross-sectional narrowing increased from 34 +/- 10% to 85 +/- 15% as laser fluence increased from 240 mJ/cm2 to 640 mJ/cm2 (r = 0.84). Similarly, cross-sectional narrowing caused by SMC neointimal proliferation increased from 20 +/- 10% to 77 +/- 17% for a fixed surface irradiation as the depth of the most superficial arterial media decreased from 600 microns to 330 microns (r = 0.94). CONCLUSIONS: Thermal injury to the arterial wall is a potent stimulus for SMC proliferation and may necessitate reduction in laser or thermal energy used for angioplasty. Moreover, a dose-response relation exists between the degree of thermal injury and SMC proliferative response. Hence, this technique could be used as a practical model of restenosis suitable for screening therapies for inhibition of SMC proliferation.

Animals↗

Effects of acidic fibroblast growth factor on normal and ischemic myocardium.

We sought to determine the effects of acidic fibroblast growth factor (FGF) on ischemic and normal myocardium and to determine whether direct application of acidic FGF to the heart could promote angiogenesis. Eighteen dogs underwent placement of an ameroid constrictor on the left anterior descending coronary artery (LAD). Three weeks later, a left internal mammary artery (IMA) pedicle was positioned over the LAD territory, with a sponge saturated with acidic FGF (n = 12) or saline (n = 4) interposed between the pedicle and the heart. Polytetrafluoroethylene fiber or collagen I sponges were used to deliver the acidic FGF. Weekly angiography of the IMA was performed in all dogs, but significant IMA to coronary collaterals were not demonstrable in any dog. Eight dogs had histological evidence of subendocardial infarction in the LAD territory (five acidic FGF, three control, p = NS). Striking smooth muscle cell hyperplasia was present in arterioles and small arteries exclusively in areas of subendocardial infarction in all of the acidic FGF-treated dogs but in none of the control dogs (p less than 0.05). Noninfarcted myocardium appeared normal in all dogs. In two additional dogs, ameroid constrictors were not placed on the LAD, such that acidic FGF-treated sponges were placed on normally perfused myocardium of the LAD territory. Histological evaluation of those hearts revealed normal myocardium, without evidence of myocardial infarction or smooth muscle cell hyperplasia. Thus, when acidic FGF is delivered to the myocardium via an epicardial sponge in dogs whose coronary flow is compromised, acidic FGF does not cause an angiogenic response in viable myocardium but causes vascular smooth muscle cell hyperplasia in areas subjected to ischemic injury.

Animals↗

Rabbit ear model of injury-induced arterial smooth muscle cell proliferation. Kinetics, reproducibility, and implications.

Recently, considerable interest has focused on the vascular smooth muscle cell (SMC) response to injury, particularly as it relates to restenosis after angioplasty. In an effort to find an optimal experimental model of arterial SMC proliferation after injury, we examined the effects of external injury to the central artery of the rabbit ear and assessed the reproducibility, morphological changes, and time course of cellular proliferation after such an injury. With rabbits under general anesthesia, direct pressure was applied at two sites along the central artery of the ears of 19 New Zealand White rabbits. Rabbits were maintained on a diet of 2.4% fat and 0.001% cholesterol throughout the experiment. In seven rabbits examined after 21 days, marked SMC proliferation with neointimal formation was observed at all 28 sites (100%). Mean neointimal area, expressed as a percentage of the area of the tunica media, was 82 +/- 40% (range, 21-203%). Compared with the uninvolved artery displaced 2 mm from the injury site, mechanical crush caused a 38% increase in total vessel area (p less than 0.001), a 40% decrease in luminal area (p less than 0.002), and no change in the area of the media. Serial histological studies were performed 1-42 days after injury, using light and electron microscopy and bromodeoxyuridine immunohistochemistry. Beginning at day 3, activated medial SMCs were noted to migrate through defects in the internal elastic membrane, with a gradual increase in neointimal area between days 5 and 12. Peak DNA synthesis was identified in the media 5 days after injury, with proliferative activity shifting almost exclusively to the neointima thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Blood gas transport properties in endurance-trained athletes living at different altitudes.

Hemoglobin oxygen binding properties and acid-base status were investigated in Colombian athletes (A) and controls (C) from Cali (C-1000 m) and Bogotá (B-2600 m). [Hb] and Hct values were not influenced by altitude, but Hct was lower in the blood of athletes (in Cali 2.6%, in Bogotá 1.4%). Both training and altitude produced a right-shift of the standard oxygen dissociation curve (P50 in CC 28.5 +/- 0.9 mmHg, AC 31.0 +/- 1.4 mmHg, CB 29.6 +/- 1.5 mmHg) leading to highest P50 in blood of altitude athletes (32.3 +/- 1.1 mmHg). Opposite to the position of the ODC the slope "n" was only increased by altitude influence (delta "n" in controls 0.07, in athletes 0.28). The BCCO2 was increased in AC over the whole saturation range, whereas BCLac was neither significantly influenced by training nor by altitude. All altitude effects can be explained by higher [DPG] (delta[DPG] in controls 5.0 mumol/gHb, in athletes 3.9 mumol/gHb), but the cause for the training effects still remains unclear. The acid base status in altitude residents was characterized by low BE and pCO2, which was most pronounced in altitude athletes, the latter correcting the actual venous pH to normal values. No significant variations of the Hb-O2-binding properties could be detected in athletes one day after leaving high altitude when compared with blood samples of athletes taken at high altitude, whereas BE and venous pCO2 were already increased. It is concluded that high altitude athletes are favoured during aerobic and handicapped during anaerobic exercise after the rapid descent to low altitude.

Acid-Base Equilibrium↗

[The effect of a peripheral androgenic blockade on plasma lipoproteins in hirsutism patients].

We studied the effect of flutamide, a peripheral androgenic blocking agent, 500 mg daily for 28 days in 7 non ovulating patients with hirsutism. Total and HDL cholesterol, triglycerides, testosterone and dehydroepiandrosterone sulphate (S-DHEA) plasma levels were measured in patients and in 6 non ovulating control women of similar age and weight. Only basal HDL levels were lower in patients than in controls (40.2 +/- 1.6 vs 51.4 +/- 3.3 mg/dl, p < 0.01). A decrease in S-DHEA levels was observed after flutamide in patients with hirsutism (3.2 +/- 0.4 to 2.1 +/- 0.4, p < 0.01) which may be attributed to the lowering of cortisol clearance induced by the drug. Total testosterone and plasma lipoproteins remained stable. Thus, peripheral androgenic blockade does not modify the decreased levels of HDL cholesterol in non ovulating patients with hirsutism.

Adult↗

[Mirizzi syndrome: experience of 77 cases].

Mirizzi syndrome is estimated to occur in about 1% of cases requiring urgent or elective biliary tract surgery. The key anatomic finding is extrinsic compression of the common duct by a stone located in the gallbladder or cystic duct. Among patients operated on in the last 12 years we have found 77 patients meeting criteria to diagnose Mirizzi syndrome. 76% were females, usually over 40 years of age; jaundice was present in 98% and elevated alkaline phosphatase in 97% of cases. Percutaneous transhepatic cholangiography allowed the diagnosis in 32 of 41 patients. The most common surgical technique involved a patch repair of the gallbladder over the Kehr tube in 45 patients. Eight patients required biliary-jejunal bypass. Eleven patients were reoperated on for benign stenosis of the biliary tract over a 1 month to 10 year period of follow up.

Adolescent↗

Fine-needle aspiration biopsy of lymphangiographically normal lymph nodes: a negative view.

Clinical acceptance of lymphangiography has been limited primarily by a high false-negative rate. Two recent reports suggest that fine-needle aspiration biopsy of lymphangiographically normal lymph nodes can detect "silent" metastases, thereby improving lymphangiography as a staging procedure. Aspiration biopsies were performed on radiographically normal lymph nodes bilaterally in 49 patients with carcinoma of the prostate or bladder, without detecting a single metastasis. Even though fewer nodes were biopsied in each case than in the two previous studies, the results of this study cast doubts on the assertion that percutaneous aspiration biopsy of lymphangiographically normal nodes can detect most nodal metastases.

Biopsy, Needle↗

HIV-related risk behaviors and seropositivity among homeless drug-abusing women in Miami, Florida.

This article examines the multifaceted interactions among homelessness, HIV, substance abuse, and gender. Data were collected on 1,366 chronic drug users using a nationally standardized validated instrument within the Miami CARES project of a multisite federally funded program. HIV testing accompanied by pretest and posttest counseling was conducted on-site by certified phlebotomists and counselors. In addition to descriptive analyses and corresponding tests of significance, logistic regression analyses were used to clarify the complex associations between the outcome variables of homelessness and HIV, recognizing difficulties of determining temporal sequence. HIV infection was found to be 2.35 times more prevalent among homeless women than homeless men and significantly higher for homeless women. The findings indicate that among women, homelessness and HIV have a highly interactive effect increasing the vulnerability of this population and thus rendering them an extremely important priority population on which to focus public health efforts and programs.

Adolescent↗