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Biomedical subjects

F Sala

Publications and source records attributed to F Sala.

At least 37 records · Page 2Linked to original sources

Retroesophageal subclavian artery aneurysm arising from Kommerell's diverticulum.

This report describes a novel technique used for management of retroesophageal subclavian artery aneurysm arising from Kommerell's diverticulum. The procedure consists of endoaortic exclusion of the aneurysmal neck, using a prosthetic patch after sternotomy during circulatory arrest, and antegrade cold blood cerebroplegia. The advantages of this technique are avoidance of hemorrhagic complications during clamping of the aneurysmal neck, limiting of the extent of dissection of the aortic arch, and elimination of the risk of inadvertent left recurrent nerve paralysis. Antegrade cold blood cerebroplegia provides good cerebral protection and decreases the duration and consequences of extracorporeal circulation.

Aged↗

Electrophysiologic monitoring in neurointensive care.

Cumulative evidence of potential benefits of electroencephalography (EEG) and evoked potentials in the management of patients with acute cerebral damage has been confirmed. Continuous EEG monitoring is the best method for detecting nonconvulsive seizures and is strongly recommended for the treatment of status epilepticus. Continuously displayed, validated quantitative EEG may facilitate early detection of secondary cerebral insults and may play a decision-making role in the management of patients with head injury, stroke, or subarachnoid hemorrhage. Long-latency auditory evoked potentials and cognitive components constitute a new field of interest for the progress of comatose patients. Motor evoked potentials may become clinically important both in acutely injured and elective postoperative patients. In the neurointensive care units adequate techniques can be selected to answer targeted clinical questions. The efficacy can be improved by implementing educational projects based on ad hoc training of nurses and neurointensive care specialists.

Acute Disease↗

Neuroprotective role of neurophysiological monitoring during endovascular procedures in the spinal cord.

The endovascular treatment of spinal vascular malformations places the spinal cord at risk for ischemia. When these procedures are performed using general anesthesia, the neurophysiological monitoring methods currently available provide the only means by which to assess the functional integrity of sensory and motor pathways. Neurophysiological monitoring allows a warning for the neuroradiologist of impending irreversible neurological damage so that action may be taken for the prompt restoration of adequate spinal cord perfusion. Muscle motor evoked potentials (mMEPs) better reflect spinal cord perfusion in the anterior spinal artery territory than do somatosensory evoked potentials (SEPs), although their use during spinal endovascular procedures remains anecdotal in the literature. In the study reported here we assessed: (1) the feasibility of intraoperative neurophysiological monitoring, (2) the role of provocative tests with Amytal and Xylocaine, and (3) the specific but complementary role played by SEPs and mMEPs, during endovascular embolization of spinal vascular malformations and tumors. The results suggest that: (1) neurophysiological monitoring is feasible during most endovascular procedures in the spine and spinal cord under general anesthesia, (2) provocative tests enhance the safety of the procedure, (3) mMEPs are more feasible than SEPs and more sensitive than SEPs to provocative tests. We strongly suggest the use of multimodal neurophysiological monitoring and provocative tests during the endovascular treatment of spinal and spinal cord vascular lesions.

Algorithms↗

The role of intraoperative neurophysiology in the protection or documentation of surgically induced injury to the spinal cord.

Playing both neuroprotective and educational roles, intraoperative neurophysiology has become an intrinsic part of modern neurosurgery. In this article, we present evidence substantiating the neuroprotective role of intraoperative neurophysiology, specifically its capacity to help prevent injury to the corticospinal tracts and the dorsal columns during spinal cord injury.

Electric Stimulation↗

Immunomodulating effects of extracorporeal photochemotherapy in rat experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a well-established model of human multiple sclerosis that is commonly used to evaluate the possible effectiveness of new treatments in this disease. Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure currently used in several non-neurological diseases that, like multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity. In this study we examined the effect of ECP using the EAE paradigm in the Lewis rat. In our model, ECP induced a significant modulation in peripheral blood T-cell distribution, changes which are typical of EAE. Remarkably, this effect was closely correlated with the clinical and pathological results, which showed reduced severity of the disease in the ECP-treated EAE animals vs. the EAE alone rats. We conclude that ECP induces modifications in the immunological events that occur during the course of EAE in rats, thus giving support to the hypothesis that it could be used in the treatment of multiple sclerosis.

Adjuvants, Immunologic↗

Value of stent placement during percutaneous transluminal angioplasty of the iliac arteries.

BACKGROUND: To determine the benefits of stents during percutaneous transluminal angioplasty (PTA) of the iliac arteries. Retrospective analysis of our 10-year surgical experience with iliac PTA from 1988-1997 permitted comparison of results during two consecutive periods: an initial period (1988-1992), during which stents were never used, followed by a second period (1992-1997), when stenting was performed on indication. METHODS: From January 1988 to October 1997, 287 iliac PTA procedures (158 common iliac arteries, 129 external iliac arteries) were performed on 250 patients. Thirty-seven patients had two iliac lesions that were treated simultaneously. Indications for PTA included stenosis (270 cases) and chronic occlusion (17 cases). Thirty-one patients (12.4%) underwent infra-inguinal bypass in addition to PTA owing to the existence of arterial lesions at two levels. Two consecutive patient groups were defined: Group I consisted of 75 patients who underwent 86 iliac PTA procedures between January 1988 and May 1992 without stent placement; Group II consisted of 175 patients who underwent 201 iliac PTA procedures between June 1992 and October 1997, when selective stenting was performed. A total of 55 stents (35 in the common iliac artery, 20 in the external iliac artery) were placed in Group II during PTA due to unsatisfactory immediate results (dissection, residual stenosis) or occlusion. RESULTS: There was no 30-day mortality. There were 15 immediate failures of PTA: 8 in Group I (10.7%) and 7 in Group II (4%). The cumulative initial success rate was 94%. Follow-up ranged from 3 months to 102 months (mean 37 months). The cumulative primary patency rate at 4 years was 62% (58% in Group I, 64% in Group II). The cumulative secondary patency rate at 4 years (including patients who subsequently underwent repeat angioplasty procedures) was 72% (68% in Group I, 74% in Group II). CONCLUSIONS: Stents were an effective means for treatment of initial failures of PTA in patients with iliac artery occlusive disease. However, there were no significant differences in the long term results between PTA alone and PTA with selective stent placement.

Adult↗

Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene.

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.

Adult↗

Cell-based screening approach for antitumor drug leads which exploits sensitivity differences between normal and cancer cells: identification of two novel cell-cycle inhibitors.

A cell-based in vitro screening approach for identification of antitumor drug leads that exploits the differential sensitivity between normal and cancer cells was developed. It is a three-step, high-throughput screen for antiproliferative and/or cytotoxic activity measured by a 7 day MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromidel assay using small panels of proliferating primary human cells and established cancer cell lines. Proof-of-concept experiments successfully identified 11 known cancer drugs randomly mixed with 5000 test compounds. Application of this screening approach to a library of 110000 compounds allowed for the identification of several novel chemical classes of compounds active against an expanded panel of cancer cell lines in vitro. Two of the compounds representing novel mitotic inhibitors with in vivo potency against established breast cancer xenografts (MDA-MB-435) are reported here.

Antineoplastic Agents↗

Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study.

The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7. 2%) on the peripheral nervous system of Wistar rats treated for 10 consecutive days and followed-up for an additional 45 days. DMSO administration induced a dose-dependent reduction in nerve conduction velocity, with complete recovery occurring in the follow-up. No structural changes were found in the sciatic nerve at 1.8% and 3.6% DMSO concentrations, suggesting that the mechanism of action of DMSO involves a functional impairment (i.e. conduction block) similar to that already described for this substance in isolated systems. However, when DMSO was administered at the 7.2% concentration, evident structural changes were observed in the sciatic nerve, with myelin disruption and uncompacted myelin lamelle. The neurophysiological and pathological changes observed in our study are severe enough to merit careful consideration in the course of experimental studies involving DMSO as a solvent for drugs which are under evaluation for their potential neurotoxicity.

Animals↗

Renal artery revascularization in combination with infrarenal aortic reconstruction.

Associated stenosis of one or both renal arteries is not uncommon in patients with infrarenal aortic disease (aneurysm or occlusive disease) requiring surgical repair. The purpose of this retrospective study was to analyze the short- and long-term outcome of concomitant renal artery and aortic reconstruction. The present series includes 39 consecutive concomitant procedures. Simultaneous aortic and renal artery reconstruction was performed in a total of 39 (7.2%) of the 540 patients who underwent elective infrarenal abdominal aortic repair between 1987 and 1996. There were 33 men and 6 women with a mean age of 66.7 years. Twenty-eight patients presented hypertension and 7 presented renal insufficiency associated with hypertension. In all cases, the indication for operative treatment was aortic disease, i.e., aortic aneurysm in 20 cases and occlusive aortoiliac disease in 19 cases. A total of 51 renal artery revascularization procedures were performed, including bypass in 40 cases, transposition in 7, and endarterectomy in 4. Combined aortic and renal artery reconstruction gives good short- and long-term results comparable to those of isolated aortic surgery. On the basis of these findings, we think that concomitant repair is the strategy of choice for patients presenting renal artery stenosis associated with infrarenal aortic disease requiring surgical therapy.

Aged↗

Surgical management of atherosclerotic carotid artery stenosis after cervical radiation therapy.

Carotid surgery following external cervical irradiation has not been a treatment of choice. The purpose of this retrospective study was to describe the immediate and long-term outcome in a series of 17 consecutive patients who underwent operative treatment for carotid artery stenosis after radiation therapy. From 1989 to 1997, surgical treatment of carotid artery disease was carried out in a total of 723 patients. Seventeen of these patients, 14 men and 3 women, had undergone previous external cervical irradiation; their mean age was 61.7 years. The indication for radiation therapy was ear-nose-throat cancer in 14 patients and lymphoma in 3 patients. In 10 patients, irradiation was associated with cervical surgery. The mean delay between radiation therapy and carotid artery repair was 10 years. All 17 patients were considered to be in remission at the time of carotid repair. The indication for carotid surgery was asymptomatic stenosis in 6 cases (33%) and symptomatic stenosis in 12 (67%). The procedure consisted of endarterectomy in 12 cases (67%) and venous bypass in 6 (33%). The outcome for these patients was favorable, indicating that carotid artery repair following cervical radiation therapy is safe. Results are comparable to those of procedures performed in patients with no history of cervical irradiation.

Aged↗

Prognostic value of motor evoked potentials elicited by multipulse magnetic stimulation in a surgically induced transitory lesion of the supplementary motor area: a case report.

Surgery involving the supplementary motor area (SMA) places the patient at risk of transient motor deficit. To predict outcome in patients with early postoperative hypokinesis would be relevant to both the patient and the surgical team. A 15 year old girl with a large left thalamic tumour removed through a left transcallosal approach is described. Despite intraoperatively preserved muscle motor evoked potentials (mMEPs) from all limbs, elicited by multipulse electrical stimulation, she awoke with a right hemiplegia and mutism. On the first postoperative day, neurophysiological evaluation using a multipulse magnetic stimulation technique, with a train of four magnetic stimuli, confirmed the presence of mMEPs from the hemiplegic right limbs. Slight spontaneous motor activity of the right limbs and initial speech were seen later on the same day with dramatic improvement over subsequent days. It is concluded that multiple rather than single magnetic stimulation techniques may be needed to elicit mMEPs for an early postoperative differential diagnosis of SMA damage versus injury to the primary motor cortex or the corticospinal tract.

Brain Diseases↗

Gating of alpha3beta4 neuronal nicotinic receptor can be controlled by the loop M2-M3 of both alpha3 and beta4 subunits.

Previous studies have shown that the gating mechanism of alpha3beta4 neuronal nicotinic receptors is affected by a residue in the middle of the M2-M3 loop of the beta4 subunit. We have extended the study of the same location to the alpha3 subunit. Bovine alpha3beta4 receptors were mutated in position 268, substituting the residue present in wild-type receptors, i.e. leucine in alpha3 and asparagine in beta4, for an aspartate. Wild-type and mutated alpha3 and beta4 subunits were combined to form four different receptors. We have measured macroscopic currents in Xenopus oocytes elicited by nicotine, and related them to surface receptor expression measured with an epibatidine-binding essay. We also obtained single-channel recordings of the receptors to study their kinetic behaviour. The results were analysed in terms of an allosteric model with three states. We found that the effect of the mutation in the alpha3 subunit on the gating of the receptor was similar to the corresponding mutation in the beta4 subunit. The effect when both subunits were mutated was additive, suggesting that the contribution of each subunit to the gating mechanism is independent.

Animals↗

Embolization of a spinal arteriovenous malformation: correlation between motor evoked potentials and angiographic findings: technical case report.

OBJECTIVE AND IMPORTANCE: Endovascular procedures for the treatment of spinal arteriovenous malformations place the spinal cord at risk of ischemia. This report illustrates the usefulness of motor evoked potentials (MEPs) in detecting functional changes within the spinal cord motor pathways during embolization of a spinal arteriovenous malformation under general anesthesia. CLINICAL PRESENTATION: A 28-year-old man presented with a history of progressive lower extremity numbness and weakness followed by bladder dysfunction. Magnetic resonance imaging and angiography disclosed a T11-T12 spinal arteriovenous malformation. INTERVENTION: During the endovascular procedure, before injection of particles, the disappearance of MEPs from the tibialis anterior muscle led to prompt angiographic reevaluation, which disclosed the arrest of spinal blood flow secondary to radiculomedullary artery occlusion by the catheter. Embolization and catheter withdrawal were followed by temporary recovery of spinal blood flow and MEPs. A second arrest of spinal cord blood flow, caused by severe vasospasm of the feeding radiculomedullary artery, was documented by a control angiogram, and its functional relevance was revealed by a second disappearance of MEPs. The therapeutic effect of papaverine infusion and induced moderate hypertension was confirmed angiographically by complete reopacification of the anterior spinal artery and confirmed neurophysiologically by the complete recovery of MEPs. At the end of the procedure, no additional neurological deficits were noted. CONCLUSION: During spinal cord embolization, MEPs may play a critical role in early detection of spinal cord dysfunction by aiding in the prevention of damage to the spinal cord as well as by predicting the clinical outcome.

Adult↗

Role of glycemia in acute spinal cord injury. Data from a rat experimental model and clinical experience.

While experimental and clinical evidence indicates that in brain injury blood glucose increases with injury severity and hyperglycemia worsens neurological outcome, the role of blood glucose in secondary mechanisms of neuronal damage after acute spinal cord injury has not yet been investigated. Data from spinal cord ischemia models suggests a deleterious effect of hyperglycemia, likely due to enhanced lactic acidosis, which is primarily dependent on the amount of glucose available to be metabolized. The purpose of this study is to summarize preliminary experimental and clinical observations on the role of blood glucose in acute spinal cord injury. Between 1995 and 1996 we used the New York University (NYU) rat spinal cord injury model to test the following hypotheses: 1) Blood glucose levels increase with injury severity. 2) Fasting protects from hyperglycemia and prevents secondary damage to the spinal cord. 3) Postinjury-induced hyperglycemia (dextrose 5% 2 gm/Kg) enhances spinal lesion volume. From a clinical perspective, we reviewed blood glucose records of 47 patients admitted to the Department of Neurosrgery in Verona, between 1991 and 1995, within 24 hours of acute spinal cord injury in order to determine: a) the incidence of hyperglycemia (> 140 mg/dl); b) the correlation between blood glucose and injury severity; and c) the role of methylprednisolone in affecting blood glucose. Results indicate that in a graded spinal cord injury model: 1) Early after injury, more severe contusions support significantly higher blood glucose levels. 2) Fasting overnight does not directly affect spinal cord lesion volume but influences blood gases, and we observed that a slightly systemic acidosis plays a minor neuroprotective role. Fasting also ensures more consistent normoglycemic baseline blood glucose values. 3) Postinjury-induced moderate hyperglycemia (160-190 mg/dl) does not significantly affect spinal cord injury. In the clinical study, we observed that during the first 24 hours after spinal cord injury: a) Glycemia ranges between 90 and 243 mg/dl (mean value 143 mg/dl), and close to 50% of the patients present blood glucose values higher than normal. b) Methylprednisolone administration is not associated to significantly higher blood glucose levels. c) There is a trend for larger glucose rises with more severe injury.

Animals↗

Brain tumors in children under 3 years of age. Recent experience (1987-1997) in 39 patients.

Brain tumors in children under 3 years of age differ in clinical presentation and pathological behavior from those in older patients. In this study, we reviewed data from 39 children (24 males and 15 females) under 3 years of age who were treated for intracranial brain tumors since the introduction of magnetic resonance imaging. The purpose was to assess correlations between clinicoradiological and treatment-related factors, and their impact on prognosis. The following factors were analyzed: sex, age, duration of symptoms, intracranial hypertension on admission, tumor location, surgical removal and histology. Associations between these factors and correlations with prognosis were determined using bivariate analyses (chi(2) test) and Kaplan-Meier survival curves. Collins' concept of a period of risk recurrence was tested. Mean follow-up was 41 months (range 0-136). In March 1998, 20 children were still alive (51.2%) with a mean survival time of 65 months (range 2-136). The incidence of supratentorial tumors was significantly higher in children less than 1 year old (p = 0.027). Lateral tumors were 9/10 (90%) supratentorial versus only 7/26 (27%) midline tumors (p = 0.001). Outcome (dead or alive) was significantly better (p = 0.037) for low-grade astrocytomas (9/12 = 75% survival) when compared to ependymomas (2/6 = 33%) and primitive neuroectodermal tumors (3/12 = 25%). Total tumor removal was achieved in 20 cases and was associated with a better outcome (65 vs. 33% survival; p = 0.049). Survival analysis confirmed a worse prognosis for children with ependymomas and primitive neuroectodermal tumors (p = 0.011) and revealed a worse survival for children with intracranial hypertension on admission (p = 0.047). Total tumor removal was associated with a longer survival, although not significantly (p = 0. 077). Finally, we found no exceptions to Collins' law.

Brain Neoplasms↗

A residue in the middle of the M2-M3 loop of the beta4 subunit specifically affects gating of neuronal nicotinic receptors.

An aspartate residue in the M2-M3 loop of neuronal nicotinic receptor alpha7 subunits is a major determinant of the channel functional response. This residue is conserved in most beta4 subunits, e.g. human and rat, but not in others, e.g. bovine. We have used these differences to examine the mechanism by which this residue alters the functional properties of alpha3beta4 receptors. Having ruled out an effect on the macroscopic binding ability of the agonist, the level of receptor expression, or the single channel conductance, the results suggest that receptors lacking that residue have a deficient coupling between binding and gating.

Animals↗