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Biomedical subjects

F Nicosia

Publications and source records attributed to F Nicosia.

At least 19 recordsLinked to original sources

Wernicke's encephalopathy in a malnourished surgical patient: clinical features and magnetic resonance imaging.

We report a clinical and neuroradiological description of a severe case of Wernicke's encephalopathy in a surgical patient. After colonic surgery for neoplasm, he was treated for a long time with high glucose concentration total parenteral nutrition. In the early post-operative period, the patient showed severe encephalopathy with ataxia, ophthalmoplegia and consciousness disorders. We used magnetic resonance imaging (MRI) to confirm the clinical suspicion of Wernicke's encephalopathy. The radiological feature showed hyperintense lesions which were symmetrically distributed along the bulbo-pontine tegmentum, the tectum of the mid-brain, the periacqueductal grey substance, the hypothalamus and the medial periventricular parts of the thalamus. This progressed to typical Wernicke-Korsakoff syndrome with ataxia and memory and cognitive defects. Thiamine deficiency is a re-emerging problem in non-alcoholic patients and it may develop in surgical patients with risk factors such as malnutrition, prolonged vomiting and long-term high glucose concentration parenteral nutrition.

Ataxia↗

Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.

Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping (SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease.

Adolescent↗

Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene.

Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.

Alzheimer Disease↗

BACE-2 is overexpressed in Down's syndrome.

Brain deposition of the amyloid-beta protein (Abeta) is a frequent complication of Down's syndrome (DS) patients. Abeta peptide is generated by endoproteolytic processing of Abeta precursor protein by gamma and beta secretases. Recently a transmembrane aspartyl protease, BACE, has been identified as the beta-secretase, and its homologous BACE-2 has also been described. BACE-2 gene resides on chromosome 21 in the obligate DS region. It cleaves Abeta precursor protein at its beta site and more efficiently at a different site within Abeta. In the present study we characterized the BACE-2 gene and protein expression in the DS patients and healthy control. We analyzed, by using a nonradioactive ribonuclease protection assay, the levels of BACE-2 mRNA expression in primary skin fibroblasts. The analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in the DS group compared to the levels observed in the control group. Western blot analysis revealed no difference between DS and control in BACE-2 protein levels in the intracellular compartment. In the medium conditioned by fibroblast, we revealed an evident secretion of BACE-2 protein, represented by two different molecular weights, remarkably increased in DS fibroblasts. BACE-2 overexpression was also confirmed in the DS fetal brains and human neural embryonic DS stem cells in which conditioned media BACE-2 was secreted. These data highlight the importance of the extracellular compartment where BACE-2 overexpression could play a role in plaque formation in DS patients.

Adult↗

Detection of the presenilin 1 COOH-terminal fragment in the extracellular compartment: a release enhanced by apoptosis.

Mutations in gene encoding presenilin 1 (PS1) are responsible for the majority of familial Alzheimer's disease (FAD) cases. We studied PS1 localization in HEK293 cells and in primary neurons obtained from rat cortex and hippocampus. We first demonstrated that PS1-CTF, but neither PS1-FL nor PS1-NTF, is released into the medium as a soluble and membrane-associated form. After induction of apoptosis with staurosporine (Sts), we observed a dramatic increase in the level of PS1-CTF in the medium, both in HEK293 and in primary neurons. Immunocytochemical analysis suggested that the release of PS1-CTF might occur via membrane shedding. Abeta(1-42) treatment reduced PS1-CTF extracellular levels. This decrease was strongly associated to an impaired secretion of sAPP fragments, thus suggesting a role of PS1-CTF in the control of trafficking and generation of APP fragments.

Alzheimer Disease↗

Peptic ulcer bleeding: comparison of two hemostatic procedures.

OBJECTIVE: Bleeding is a serious complication of peptic ulcer. Endoscopic injection therapy is accepted as a homeostatic endoscopic treatment in acute nonvariceal of upper GI hemorrhages, particularly in bleeding peptic ulcers. The risk of rebleeding is predicted by the endoscopic appearance of ulcer features classified according to Forrest's criteria. METHODS: Two hundred twenty-three patients were selected from 1,003 emergency upper endoscopies for GI bleeding. According to Forrest's criteria, 99 well-matched patients with ulcers F1 and F2 were considered at risk of rebleeding; 54 patients (group A) received local ulcer injection of epinephrine solution 1:10,000, whereas (group B) patients were treated with local epinephrine injection and then with endoscopic Hemoclips. (1) We considered the control of bleeding, the number of rebleeding episodes, the need for emergency surgery, and mortality. RESULTS: Bleeding ulcers stopped completely in 83.3% group A patients, and in 95.6% group B patients (p = not significant). In a subset of F1b patients the rebleeding rate was 31 % for group A and 0% for group B (p < 0.05). There was no mortality as a result of the procedure. There was a trend toward reducing surgery in favor of the combined therapy (0% vs 7.4%). No differences were found in transfusion requirements or mean hospitalization days. CONCLUSIONS: We conclude that endoscopic injection of l:10,000 epinephrine solution alone and epinephrine solution plus application of Hemoclips are equivalent therapies in treating bleeding and rebleeding from peptic ulcers. There was no difference between therapies in terms of need for surgery or mortality. Possibly combination therapy is more effective in treating ulcers that are actively oozing.

Adolescent↗

Diagnosis and therapy of intrathecal bleeding.

AIM: Define pathophysiology, epidemiology, diagnosis and therapy in case of spinal bleeding after central neural blockade (CNB). METHODS: Spinal epidural hematoma (SEH) following CNB may occur due to vascular trauma from needle/catheter placement and can occur in subdural and epidural spaces. Epidural artery bleeding seems the source of SEH: the damage mechanism depends on compression and neural vascular ischemia of cord, nerve roots, ganglion and toxicity from blood cell lysis products. Incidence varies (1:150.000 - 1:500.000) but SEH may be asymptomatic. CONCLUSIONS: SEH starts with acute severe low back and/or radicular pain and neurologic signs that may progress to paraparesis, sensory loss and sphincter disturbances. After CNB, the only sign of SEH may be an unusually prolonged motor and sensory block. Symptoms may start even 96 hours after CNB and/or removal of the epidural catheter. Neurological recovery is related to severity and speed of preoperative deficits development and surgical decompression. MR imaging features (diagnostic tool of choice), including degree of cord compression, are useful to establish or confirm the diagnosis of SEH but do not influence the management or predict outcome. Hematoma resolution and severity of neurologic impairment has the greatest impact on management and outcome. Preoperative MRI information and intraoperative evidence of subarachnoid hemorrhage (SAH) and CSF leakage is important: SAH worsens outcome for its negative effect on spinal cord and cauda equina. Conservative therapy may be successful in cases with minimal neurologic deficits, despite cord compression.

Hemorrhage↗

[Postoperative pain management. Aims and organization of a strategy for postoperative acute pain therapy].

The Health Services, not only the Italian one, is under pressure because of request for improving treatment quality and the financial need for reorganization and cost-saving. It's required a rationalization of intervention, together with a careful choice of the best and cheapest techniques and the demonstration of their efficacy. The anaesthesia service activity, in a period of cost rationalization and funds restriction should be aimed to appropriate outcome measures corrected by both patient's risk factors and surgical-anaesthesiological case-mix. The development of a complete strategy for surgical pain management might run into two phases. The first phase, internal and mono-specialistic, should develop like the creation of an Acute Pain Team. The main processes are: focusing the problem (charge of the care), training, information, teaching methodology (timing, methods, drugs, techniques, etc.) and the audit (before and after changes). The main aims are the evaluation of the level of analgesia and pain relief or patient's satisfaction which are partial endpoints useful to demonstrate the improvement and the efficacy of the new pain management strategies. The second phase, multidisciplinary, is directed toward the creation of a Postoperative Evaluation Team. The main objective is to set up a collaborative clinical group able to identify the criteria for quality, efficacy and safety. The major purpose is the evaluation of major outcome measures: surgical outcome, morbidity, mortality and length of hospitalization. The improvement in the quality of postoperative pain treatment goes through a better organization and a progressive increase of the already available therapy. The achievement of the result and the quality projects depend on the interaction among staff members with different behaviours and settings. Internal teaching and training, continuous education for doctors and nurses, and external information, marketing and improvement of attractive capability of Institution, are the procedures of a growing integrated program for postoperative pain treatment. The organizational processes should interact effectively with a plan of education, updating, revision and information in a definite development timing. It should be emphasized a collaborative, interdisciplinary approach to pain control, assessment and treatment, including all the members of the health care team, with an input from the patient and a protective collaboration from the Institution. The development of a postoperative care team must be considered as part of the largest project for "a Painfree Hospital". It represents a keystone of a Institutional Quality Assurance Plan for health care providers, patients (customs) and Institution.

Acute Disease↗

Do pipecuronium and rocuronium affect human bronchial smooth muscle?

BACKGROUND: Muscle relaxants affect nicotinic and muscarinic receptors. Interaction of muscle relaxants with muscarinic receptors of human airways has been studied incompletely. METHODS: The effects of pipecuronium bromide (long-acting, nondepolarizing) and rocuronium bromide (intermediate-acting, nondepolarizing) on prejunctional and postjunctional muscarinic receptors were studied in 96 isolated human bronchial rings from 12 patients. Contractile isometric responses to electric field stimulation of pilocarpine-stimulated and nonstimulated M2 muscarinic receptors were compared before and after incubation with the two muscle relaxants. The effect on postjunctional muscarinic receptors was studied by comparing acetylcholine concentration-response curves before and after incubation with the two muscle relaxants. RESULTS: Pipecuronium bromide, but not rocuronium bromide, inhibited pilocarpine-stimulated prejunctional M2 muscarinic receptors. Neither pipecuronium bromide nor rocuronium bromide had significant inhibitory effects on nonstimulated M2 muscarinic receptors and on postjunctional M3 muscarinic receptors. CONCLUSIONS: The inhibitory effect of pipecuronium bromide on pilocarpine-stimulated prejunctional M2 muscarinic receptors occurred at clinical concentrations.

Acetylcholine↗

Inhibition of airway constriction by opioids is different down the isolated bovine airway.

BACKGROUND: Opioid agonists attenuate in isolated airways contractile responses to electrical field stimulation (EFS), and this attenuation is mediated by opioid receptors. Differences exist in the density of muscarinic and beta-adrenergic receptors between large and small airways. The authors hypothesized that the density of opioid receptors may also be different down the airway. METHODS: The effects of three selective opioid agonists (mu, kappa, delta) on EFS-induced contractions were compared between isolated bovine sublobar (4- or 5-mm inner diameter) and segmental (2- or 3-mm inner diameter) bronchial rings and between trachealis strips and bronchial rings. RESULTS: D-Ala2-N-MePhe4-Gly-ol5 enkephalin (DAMGO; 10(-5) M), a mu-opioid agonist, attenuated EFS-induced contractions of isolated sublobar and segmental bronchial rings at low stimulating frequencies of 0.5 Hz (P < 0.001), 2 Hz (P < 0.001), and 8 Hz (P < 0.001), but not at 32 Hz (P = 0.071). The inhibitory effect of DAMGO was antagonized by naloxone (10(-5) M) (P = 0.025). The selective kappa-opioid agonist U-50488 H (10(-5) m) attenuated EFS-induced contractions at 32 Hz (P = 0.008) and 8 Hz (P = 0.045), but not at 2-Hz (P = 0.893) or 0.5-Hz (P = 0.145) contractions. The inhibitory effects of 10(-5) M U-50488 H were not antagonized by the highly selective kappa-antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl-bis [2-hydroxy-4,4-dimethyl]-morpholinium (nor-BNI; 10(-5) M; P = 0.216) or naloxone (10[-5]) M; P = 0.065). The selective delta-agonist D-penicillamine2-D-penicillamine5-enkephalin (DPDPE) (10(-5) M) had no inhibitory effects (P = 0.256). The inhibitory effects of the selective mu-opioid agonist DAMGO were smaller (P < 0.001) and those of U-50488 H larger (P < 0.001) in trachealis strips compared with bronchial rings. CONCLUSIONS: The attenuation of EFS-induced contractions by DAMGO in isolated bovine bronchi was mediated by prejunctional opioid receptors. In contrast, the inhibitory effect of U-50488 H was probably not mediated by opioid receptors in the bronchi.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Postoperative analgesia in Italy. National survey on the anaesthetist's beliefs, opinions, behaviour and techniques in postoperative pain control in Italy.

BACKGROUND: Using a personal, anonymous questionnaire developed ad hoc, we tried to document the role, the problems and the activities of Italian anaesthetists in postoperative pain control. METHODS: A random selection-stratified by region-was made from a list of 971 hospitals. The final sample was made up of 395 departments of anaesthesia and intensive care from 369 hospitals. The completeness and consistency of each questionnaire were assessed. RESULTS: The response rate achieved was 78.9% (312 centres in 293 hospitals) with 2435 evaluable questionnaires corresponding to 30% of all Italian anaesthesia departments and 25% of Italian anaesthetists. Only 15.2% of anaesthetists are completely responsible for the postoperative analgesia (POA) (prescriptions and evaluations) and an established attitude for POA (protocols/guidelines) exists in 18 departments only. 60% of anaesthetists use routinely the intramuscular route, 55.2% the intravenous route (infusion plus bolus), and 23.7% the spinal/epidural route. Only 6.2% of the anaesthetists use the patient-controlled analgesia system. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used agents (47% NSAID vs 37.9% opioids; NSAID-opioid association 14.7%). A local anesthetics-opioids association is preferred for the spinal/epidural route (15.1%) only (local anaesthetic 4.9% only; opioids alone 2.7%). Lack of time, work organization, technique knowledge/training, trust in nursing-ward staff, difficulty in monitoring the patient on the ward, concern about opioid use leading to ventilatory depression, and administration errors are reported to be the main factors that limit an appropriate approach to postoperative pain (POP), the correct use of analgesics and a free choice of POA technique. CONCLUSION: This survey shows that Italian anaesthetists do not consider the postoperative period to be their own personal work area and that POA is to be considered as a matter of individual choice.

Analgesics↗

Opioid agonists modulate release of neurotransmitters in bovine trachealis muscle.

BACKGROUND: Stimulation of opioid receptors in the airways can modulate cholinergic neurotransmission and thereby reduce bronchoconstriction. This protecting effect of opioids against bronchoconstriction may be of clinical interest. Inhalation of opioids as a method of analgesia is likely to result in an opioid concentration at airway receptors sufficient to protect against bronchoconstriction; the concentration may be insufficient when opioids are administered by conventional techniques. In addition, new selective opioids may be developed that could more selectively protect the airways against bronchoconstriction. METHODS: The effect of three selective opioid agonists on the contractile response to electric field stimulation (EFS) was studied in isolated muscle strips from four regions of the bovine trachea (upper, or laryngeal; upper middle; lower middle; lower, or carinal). RESULTS: The selective kappa agonist trans-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl) cyclohexyl benzene acetamide (U-50488 H) and the selective mu-opioid agonist D-Ala2-N-MePhe4-Gly-ol5-enkephalin (DAMGO) reduced significantly (P < 0.001 and P < 0.001, respectively) the contractile response to EFS. The attenuation of the contractile response by U-50488 H was concentration-dependent (P < 0.0001) and tended to be larger at low stimulating frequencies (P = 0.055). The attenuation of the contractile response by DAMGO was frequency-dependent (P < 0.01). The selective delta-opioid agonist D-penicillamine2-D-penicillamine5-enkephalin had no significant effect on the contractile response to EFS (P = 0.71). There were no significant differences among the four regions of the trachea in their responses to the selective opioid agonists U-50488 H (P = 0.50) and DAMGO (P = 0.44). Neither U-50488 H nor DAMGO altered the contractile response to acetylcholine P > 0.11, P > 0.21, respectively), suggesting that the opioid agonists have a prejunctional effect. The attenuation of the contractile response to EFS by U-50488 H was partially but significantly antagonized by 10(-5) M naloxone (P < 0.01) and by 10(-5) and 10(-6) M of the selective kappa-opioid antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl- bis [2-hydroxy-4,4-dimethyl-morpholinium] (P < 0.05). Naloxone (10(-5) M) abolished the inhibitory effect of DAMGO, suggesting that opioid receptors are involved in the attenuation of the contractile response to EFS afforded by DAMGO and U-50488 H. CONCLUSIONS: We conclude that prejunctional kappa- and mu-opioid receptors attenuate the contractile response of isolated bovine trachealis muscle to EFS by inhibiting cholinergic neurotransmission. This effect is uniform throughout the trachealis muscle. delta-Opioid receptors are apparently not present in the bovine trachealis muscle. Caution must be used in extrapolating these results to the intact human. In this study little or no inhibitory effect of the opioids was observed at concentrations expected at airway receptor sites when administered by conventional techniques. However, the effect may be large enough to protect against bronchoconstriction when nebulized opioids are administered by inhalation.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

The transverse rectus abdominis musculocutaneous flap for breast reconstruction in obese patients.

Transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction has often been considered contra-indicated in obese women. The morphological characteristics peculiar to this population, however, make obese women ideal candidates for this procedure because the reconstructed breast must often match a large ptotic contralateral breast. About one-third of our postmastectomy patients are corpulent, middle-aged women with "Mediterranean" body structures. Thirty-four obese women underwent TRAM flap breast reconstruction from 1985 to 1988. According to the Body Mass Index, 23 women had type II obesity and 11 had type III obesity. The preoperative and postoperative management and the surgical procedure were adapted to this particular group of women. The complication rate in this series of women was superior to that of a nonobese population; however, no severe complications were observed. The majority of women were extremely satisfied with aesthetic results; the surgeons also judged the final cosmetic outcome to be very favorable and, indeed, superior to that obtainable with simpler methods. Obesity uncomplicated by other risk factors does not represent an absolute contraindication to TRAM flap procedure.

Abdominal Muscles↗

[Complications of prolonged peridural catheterization in the treatment of cancer pain with opioids].

40 patients in 2 groups of 20 and all subjected to peridural catheterisation for the intermittent infusion of pain-killing opiates are examined. Different catheters and different lengths of time (47.55 and 62.15 days) were adopted for the two groups. Nine different parameters were used in examining the long-term complications. A statistically significant difference was found in three of these parameters. The report concludes with some general remarks on the use of peridural opiates in advanced cancer patients.

Adrenal Cortex Hormones↗