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Biomedical subjects

M Fragoso

Publications and source records attributed to M Fragoso.

17 recordsLinked to original sources

Axonal regeneration into Schwann cell grafts within resorbable poly(alpha-hydroxyacid) guidance channels in the adult rat spinal cord.

Axonal growth and myelination in a SC graft contained in a resorbable tubular scaffold made of poly(D,L-lactic acid) (PLA50) or high molecular weight poly(L-lactic acid) mixed with 10% poly(L-lactic acid) oligomers (PLA(100/10)) were studied for up to 4 months after implantation in the completely transected adult rat thoracic spinal cord. The PLA50 tubes collapsed soon after implantation and, consequently, compressed the graft inside, leading to only occasional thin cables with SCs and a low number of myelinated axons: 17 +/- 6 at 1 and 158 +/- 11 at 2 months post-grafting. The cable contained 32 +/- 23 blood vessels at 2 weeks, 55 +/- 33 at 1 month and 46 +/- 30 at 2 months after implantation. PLA(100/10) tubes, on the other hand, were found to break up into large pieces, which compressed and sometimes protruded into the tissue cable inside. At all time points studied, however, cables contained SCs and were well vascularized with 414 +/- 47 blood vessels at 2 weeks, 437 +/- 139 at 1, 609 +/- 134 at 2 and 396 +/- 95 at 4 months post-grafting. The number of myelinated axons was 712 +/- 509 at 1 month, 1819 +/- 837 at 2 months and 609 +/- 132 at 4 months post implantation. These results demonstrated that fiber growth and myelination into a SC graft contained in a resorbable PLA(100/10) tube increases over the first 2 months post-implantation but decreases thereafter. Changes in geometry of both types of polymer tubes were detrimental to axonal regeneration. Future research should explore the use of polymers that better retain the appropriate mechanical, geometrical and permeability properties over time.

Animals↗

A general method for estimating deformation and forces imposed in vivo on bioprosthetic heart valves with flexible annuli: in vitro and animal validation studies.

BACKGROUND AND AIM OF THE STUDY: The use of flexible structures within cardiovascular prostheses such as valves, stents and vascular grafts has been proposed as a means of more closely modeling native mechanics, and thereby reducing the biomechanical problems associated with rigid materials. However, the design of such materials has been hampered by the paucity of quantitative information on the in-vivo behavior of such structures. The aim of this study was to explore the use of 3D ultrasound imaging coupled with finite element analysis (FEA) as a tool to estimate deformation and forces imposed in vivo on a novel bioprosthetic valve design. METHODS: The method was first tested using in-vitro static loading conditions, where good agreement between displacements seen on video and those obtained from application of the identical force within the finite element program was seen. The method was then tested in a porcine model with valves implanted in the mitral position. Images of the deforming annular ring were obtained over the cardiac cycle using 3D intravascular ultrasound; these images were fed into the FEA program for calculation of reaction forces. RESULTS: Results in vitro showed that a force of 2.7-8.0 Newtons (N) was required to produce a deformation of between 1.0 and 3.0 mm in the radial direction. A time history of deformation and force around the ring of the valve stent could be obtained for the in-vivo conditions. These results revealed a maximum deformation of 0.5-1.7 mm along the short axis (anteroposterior) of the mitral valve. Coupled to this, a peak reaction force of 4.4-13.9 N was found at the points corresponding to maximal deflection. Both deformation and reaction force reached maximum during atrial contraction. CONCLUSION: This method provides an accurate means of estimating deformation and corresponding forces imposed in vivo on intracardiac prostheses. The results provide information on the dynamic behavior of the mitral valve annulus. Such information should be useful in the design of flexible cardiovascular prostheses.

Animals↗

Poly(alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord.

Future surgical strategies to restore neurological function in the damaged human spinal cord may involve replacement of nerve tissue with cultured Schwann cells using biodegradable guiding implants. We have studied the in vitro and in vivo degradability of various aliphatic polyesters as well as their effects on rat Schwann cells in vitro and on spinal cord tissue in vivo. In vitro, cylinders made of poly(D,L-lactic-co-glycolic acid) 50:50 (PLA25GA50) started to degrade at 7 days, compared with 28 days for cylinders made of poly(D,L-lactic acid) (PLA50). This faster degradation of PLA25GA50 was reflected by a much higher absorption of water. In vivo, after implantation of PLA25GA50 or PLA50 cylinders between the stumps of a completely transected adult rat spinal cord, the decrease in molecular weight of both polymers was similar to that found in vitro. In vitro degradation of poly(L-lactic acid) (PLA100) mixed with increasing amounts of PLA100 oligomers also was determined. The degradation rate of PLA100 mixed with 30% oligomers was found to be similar to that of PLA50. In vitro, PLA25GA50 and the breakdown products had no adverse effect on the morphology, survival, and proliferation of cultured rat Schwann cells. In vivo, PLA25GA50 cylinders were integrated into the spinal tissue 2 weeks after implantation, unlike PLA50 cylinders. At all time points after surgery, the glial and inflammatory response near the lesion site was largely similar in both experimental and control animals. At time points later than 1 week, neurofilament-positive fibers were found within PLA25GA50 cylinders or the remains thereof. Growth-associated protein 43, which is indicative of regenerating axons, was observed in fibers in the vicinity of the injury site and in the remains of PLA25GA50 cylinders. The results suggest that poly(alpha-hydroxyacids) are likely candidates for application in spinal cord regeneration paradigms involving Schwann cells.

Animals↗

Effects of an anti-exospore monoclonal antibody on microsporidial development in vitro.

In this study we evaluated the effects of the anti-microsporidial exospore monoclonal antibody 3B6, recognizing 3 Encephalitozoon species, Encephalitozoon intestinalis (Syn. Septata intestinalis), Encephalitozoon cuniculi, and Encephalitozoon hellem on microsporidial growth in vitro. Pre-treatment of spores for 24 h with mAb 3B6 resulted in 21-29% fewer infected host cells 4 days after inoculation of the cultures compared to cultures pre-treated with medium or an irrelevant isotype control mAb (P < 0.001). Fewer intracellular spores (1.2 +/- 0.2) in infected cells were found when mAb 3B6 was present in cultures compared to cultures with medium alone (4.3 +/- 0.8) or an irrelevant isotype control mAb (4.2 +/- 0.9; P < 0.001). This decrease appeared not to be dependent on time of exposure, mAb concentration, or presence of complement. It is concluded that antibodies, particularly those directed to potential neutralizing-sensitive epitopes on spores, may have a role in the control of microsporidial growth in vitro.

Animals↗

Assessing Photofrin uptake in atherosclerosis with a fluorescent probe: comparison with photography and tissue measurements.

The purpose of this study was to assess Photofrin porfimer sodium (P*) concentration in atherosclerotic plaque (ASP) using a fluorescence detector (Fluoroprobe) compared with fluorescent photography and chemical extraction of P*. ASP was created in the aortoiliac segments of Yucatan miniswine by a combination of balloon endothelial injury and 2% cholesterol and 15% lard diet for 7 weeks. At that time, swine were given P* I.V. in one of the following single dosages: Group I, 2.5; Group II, 1.0; or Group III, 0.5 mg/kg. Swine were sacrificed 24 hours later and aortoiliac and control carotid artery segments removed. Fluorescence was determined from these segments using photographic techniques, the Fluoroprobe, and a spectrofluorometer after chemical extraction. ASP were identified in all swine using photography and the Fluoroprobe. The intensity of fluorescence measured with the Fluoroprobe for Groups I to III was 1,098 +/- 524, 471 +/- 337, and 295 +/- 173 units, respectively (P < 0.01). The tissue concentration of P* in ASP from each group was 130.4 +/- 82.7, 10.0 +/- 1.2, and 9.1 +/- 0.6 ng/g, respectively (P < 0.01). There was a linear correlation between the fluorescence intensity measured with the Fluoroprobe and the extracted tissue concentration (r = 0.88, P < 0.0001). This study showed that a fluorescent detector such as the Fluoroprobe accurately detects the uptake of P* into atherosclerotic plaque.

Animals↗

Determining the optimal dose of Photofrin in miniswine atherosclerotic plaque.

The purpose of this study was to determine the lowest dose of Photofrin (P) that would produce a 3:1 or greater ratio between atherosclerotic (AS) and control arterial walls. Aortoiliac AS was created in 24 Yucatan miniswine by a combination of balloon endothelial injury and 2% cholesterol and 15% lard diet for 7 weeks. Arteriography was then performed to demonstrate AS lesions. Following this, swine were given intravenously P in one of the following single dosages: 2.5, 1.0 or 0.5 mg/kg. Twenty-four hours later, swine were sacrificed and aortoiliac and control carotid artery segments removed and photographed with ultraviolet light to differentiate fluorescent from nonfluorescent areas. Arterial specimens were submitted for histologic analysis and chemical extraction for determination of fluorescence using a spectrofluorometer. Tissue concentration (ng/g tissue) of P from AS vessels were: Group I, 130.4 +/- 82.7; Group II, 10.0 +/- 1.2; and Group III, 9.1 +/- 0.6, respectively (P < 0.05). Ratios of P concentration in AS: control vessels were: Group I, 8.1 +/- 13.7; Group II, 1.1 +/- 0.2; and Group III, 0.9 +/- 0.1, respectively (P < 0.05). These results demonstrated that a P dose of 2.5 mg/kg provided at least a 3:1 ratio between AS: control artery wall.

Animals↗

In vitro and in vivo uptake of benzoporphyrin derivative into human and miniswine atherosclerotic plaque.

Benzoporphyrin derivative (BPD) has been demonstrated to be a new potent photosensitizer for photodynamic therapy (PDT). Although most of the work on BPD has been focused on its potential applications for cancer treatment, BPD may have potential clinical uses in the treatment of atherosclerosis. The purpose of this study was to determine in vitro and in vivo uptake of BPD into atherosclerotic plaque. Samples of atherosclerotic human femoral and popliteal arteries were incubated with BPD-monoacid, ring A (BPD-MA) for 1 h in the following concentrations: 1, 5, 10, 20, 30 and 40 micrograms/mL. Fluorescence from all samples was determined by chemical extraction with a spectrofluorometer. The tissue concentration for human arteries was 0.37 +/- 0.03, 2.78 +/- 1.5, 3.6 +/- 1.91, 7.15 +/- 2.36, 8.06 +/- 3.09 and 14.6 +/- 4.81 micrograms/g, respectively. In addition, three miniswine were rendered atherosclerotic and given BPD 2.0 mg/kg intravenously. The concentration of BPD-MA in miniswine aorta was 93-190 ng/g and the plaque/normal ratio was 1.7-3.5. For miniswine iliac arteries, the [BPD-MA] was 60-178 ng/g and the plaque/normal ratio was 1.1-3.3. Normal miniswine carotid artery contained 54 ng/g. This study showed that BPD-MA was taken up in atherosclerotic vessels both in vitro and in vivo and may have potential for PDT of atherosclerosis.

Animals↗

Synaptic transmission through cat lumbar ascending sensory pathways is suppressed during active sleep.

1. Few data are available that describe the evoked activity of spinal cord sensory tract neurons as a function of behavioral state. Accordingly, experiments were performed in which ascending volleys were recorded extracellularly within the spinoreticular (SRT), spinothalamic (STT), and spinomesencephalic (SMT) tracts located in the ventrolateral reticular formation in response to low-intensity electrical stimulation of the contralateral sciatic nerve in the chronic unanesthetized, behaving cat during naturally occurring episodes of wakefulness, quite sleep, and active sleep. 2. During episodes of wakefulness and quite sleep sciatic nerve stimulation produced a low-amplitude and long-duration orthodromic field potential that did not differ in amplitude or waveform. However, during the corresponding episode of active sleep, the sciatic nerve-induced orthodromic field potential was markedly suppressed or abolished. 3. The effects of sustained microiontophoretic applications of inhibitory amino acid agonists, glycine, or gamma-aminobutyric acid during wakefulness or quite sleep markedly suppressed the antidromic field potential recorded from nearby VII motoneurons but did not alter the sciatic nerve-evoked orthodromic field potential, indicating that the sciatic response was recorded from ascending axons of passage emanating from lumbar spinal neurons. We suggest that lumbar neurons comprising the SRT, STT, and SMT tracts are subjected to a descending suppressor drive that is activated specifically during the behavioral state of active sleep.

Afferent Pathways↗

The natural history of intimal flaps caused by angioscopy.

UNLABELLED: This study tried to determine the natural history of angioscopy-induced arterial intimal flaps as assessed by video angioscopy, light and transmission electron microscopy. Eight mongrel dogs were anesthetized and bilateral femoral and carotid arteries surgically exposed. A 3.0 mm American Edwards angioscope was inserted into each artery and passed vigorously until an intimal flap was visualized by angioscopy. The location of intimal flaps was externally marked with 6-0 polypropylene adventitial sutures. Animals were then recovered and follow-up angioscopy performed at one, two, three, and four week intervals. Following repeat angioscopy, all animals were sacrificed and vessels perfusion-fixed in situ with 2.5% glutaraldehyde in 0.1 M sodium cacodylate. A total of 37 intimal injuries were created (immediate, n = 10; one week, n = 8; two weeks, n = 4; three weeks, n = 8; four weeks, n = 7). No arterial thrombosis occurred following intimal flap formation. Only one of 37 (2.7%) lesions progressed to a hemodynamically significant stenosis. Histology of immediate lesions demonstrated deep intimal fractures extending into the tunica media. Complete healing of intimal flaps was observed by follow-up angioscopy in zero of eight lesions by one week, zero of four lesions by two weeks, one of eight lesions by three weeks, and four of seven lesions by four weeks (p = 0.02). Light and electron microscopy confirmed the angioscopic intimal fractures and regrowth of denuded endothelium. CONCLUSION: follow-up angioscopy and microscopy one month after angioscopy-induced arterial intimal trauma demonstrated a significant trend towards complete endothelial healing.

Animals↗

Intraoperative balloon angioplasty: a surgical approach.

Percutaneous balloon angioplasty is a recognized treatment for peripheral atherosclerosis involving the iliac and femoropopliteal segments. From their experience in 38 patients the authors have examined the efficacy of intraoperative balloon angioplasty for tandem lesions requiring both balloon angioplasty and surgical intervention. Between January 1988 and July 1990, 43 intraoperative balloon angioplasties were performed in 19 women and 19 men who required inflow or outflow angioplasty in addition to surgical bypass. The indication for surgery was incapacitating claudication in 32 (74%) patients and limb salvage in 11 (26%) patients. Initial technical success was achieved in 17 (89%) of 19 patients who required iliac surgery and in 22 (92%) of 24 patients who required femoropopliteal balloon dilatations. There were four major complications (9%), all requiring surgical intervention. In two cases there was dissection with thrombosis and in two cases failure to improve the pressure gradient. Patients were followed up for up to 24 months. Two of the inflow angioplasties failed between 6 and 9 months. Two of the outflow angioplasties failed between 12 and 15 months. Three patients died in the follow-up period, two from myocardial infarction. In the authors' experience intraoperative balloon angioplasty has proven a worthwhile adjunct for tandem lesions in the iliac and femoropopliteal segments.

Aged↗

Stenosis following laser thermal angioplasty--a blinded controlled randomized study between aspirin against Probucol.

Long-term patency of vascular angioplasties is limited by stenosis from neointimal hyperplasia or progressive arteriosclerosis. This study evaluated the hypothesis that ASA (an antiprostaglandin) or Probucol (an antioxidant) may be useful in preventing stenosis following laser thermal angioplasty. Aortoiliac arteriosclerosis was induced in 17 female New Zealand white rabbits with a combination of endothelial denudation (4 Fr. Fogarty balloon catheters) and 2% cholesterol-supplemented diet for 6 weeks. All rabbits then underwent arteriography and were immediately randomized to one of three groups: Group I (n = 6), control, laser but no adjunctive therapy; Group II (n = 5), laser and ASA 10 mg/kg/day; Group III (n = 6), laser and 1% Probucol diet. Retrograde laser thermal angioplasty was performed with a 1-mm coronary Laserprobe. Six watts of argon laser energy was delivered for a single 5-sec pulse using a continuous motion from the right common iliac artery to the aorta. Pre- and postlaser arteriography was performed in all groups. Rabbits were sacrificed 1 month following laser angioplasty, and aortoiliac sections were taken after in situ perfusion fixation with paraformaldehyde and 0.05% glutaraldehyde. Serial 5-mm segments, proximal to the aortic bifurcation and distally from the same, were taken, stained, and evaluated by quantitative morphometry. From each segment, lesion area and lesion area/internal elastic laminae area were evaluated and compared. Serum cholesterol increased from 60.8 +/- 19.5 to 1494.7 +/- 12.7 mg% following institution of the cholesterol diet (P less than 0.05). Arteriosclerotic lesions were observed in all rabbits and maximally located around the common iliac artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Laser↗

Hematuria and microalbuminuria after a 100 kilometer race.

An investigation into hematuria and microalbuminuria induced by prolonged physical exercise was carried out by studying 26 runners who took part in a 100 km race by collecting urine samples before, after the race, and 24 hours later. Microscopic hematuria was present in two runners before the race. After this strenuous exercise there was macroscopic hematuria in five runners (19.2%) and microscopic hematuria in nine (34.6%). On examination by phase contrast microscopy there were neither dysmorphic erythrocytes nor red cell casts. Albuminuria was measured by radial immunodiffusion and was expressed as Ualb/Ucreat and Ualb/Uosm ratios. Clinical albuminuria was found in five runners with macroscopic hematuria, and microalbuminuria in 13 of the 21 remainders; in 6 of them it was associated with microscopic hematuria. Twenty-four hours later all of the results were normal with the exception of the five runners who have had macroscopic hematuria and another one with microalbuminuria without hematuria. We conclude that determination of albumin excretion in runners after exercise should be made as well as hematuria, and particular attention should be paid to cases of severe and/or prolonged microalbuminuria, since such individuals may be at risk of renal disease.

Adult↗

Transfusion therapy.

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Blood Transfusion↗

[Transient global amnesia and vascular risk factors].

INTRODUCTION: Transient global amnesia (TGA) is a clinical syndrome determined by an episode of less than 24 hours consisting of temporo-spatial disorientation with retrograde and anterograde amnesia followed by complete recovery. OBJECTIVES: To determine whether the presence or absence of vascular risk factors (VRF) in patients with TGA is associated with different clinical data and/or examination findings. PATIENTS AND METHODS: A retrospective study was made of two groups of 13 and 12 patients with TGA, who presented with and without VRF, respectively. The following variables were determined: VRF, age, a previous history of migraine, triggering factors, duration and repetition of the episodes, associated neurological symptoms and findings obtained by neuroimaging, eco-Doppler of the supra-aortic trunks and transcranial Doppler. The data were subjected to statistical analysis by univariate analysis with Fischer's exact probability test. RESULTS: The statistical studies showed no significant differences between the variables obtained in the two groups of patients. CONCLUSIONS: Transient global amnesia has been particularly related to migraine, epilepsy and cerebral vascular pathology, although its aetiology has not been fully determined. In this study we compare clinical data between the two groups of patients with and without VRF who have had TGA. The lack of significant differences between them tends to rule out a vascular aetiology as the sole cause of this syndrome. Recently Leao's propagated depression has been suggested as the physiopathological mechanism involved. According to this theory, the vascular pathology might act as the trigger but probably not as the aetiological factor. The findings of our study may support this thesis.

Aged↗

[Essential mixed cryoglobulinemia as a cause of ischemic cerebrovascular accident].

INTRODUCTION: Involvement of the central nervous system in patients with essential mixed cryoglobulinaemia is rare, and there are few cases described in the medical literature. Moreover, the mechanism by which lesions are produced in the central nervous system is still not clear. CLINICAL CASE: We describe the case of a 35 year old woman who presented with dysarthria, weakness and paraesthesia of her left limbs and left central facial paralysis of sudden onset. Vascular studies showed the presence of IgG-IgM polyclonal positive cryoglobulins and polymerase chain reaction (PCR) showed hepatitis C virus to be present. Cerebral magnetic resonance showed ischemic lesions in the tail of the right caudate nucleus and right corona radiata and the posteromedial part of the right putamen. Other investigations were negative or normal. CONCLUSIONS: In young patients with cerebral vascular pathology the possibility of hepatitis C and essential mixed cryoglobulinemia should be considered, especially when the transaminases are raised as in our patient. We consider that the physiopathological mechanisms must be related to factors which determine a prothrombotic state in the arterial bed involved.

Adult↗

[Trigeminal sensory neuropathy and lupus anticoagulant positive: cause or coincidence?].

INTRODUCTION: Trigeminal sensory neuropathy (TSN) is a rare entity characterised by transient sensory disorders in one or more branches of the trigeminal nerve (TN). There are (acute or chronic) idiopathic forms as well as others that are linked to inflammatory, vascular or structural lesions. CASE REPORT: We describe the case of a female aged 30 who presented two self limited episodes of left facial hypaesthesia (second branch of the TN), with no other accompanying symptoms and which lasted 3 7 days, with complete resolution. In the study, lupus anticoagulant (LAC) positive was found in two determinations conducted at a six week interval, while the rest of the findings were either negative or within values that were considered to be normal. CONCLUSIONS: Following the description of a case of what may be idiopathic TSN, we discuss the possible relation this may have with the positive result for LAC.

Adult↗