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Biomedical subjects

M Festa

Publications and source records attributed to M Festa.

At least 19 recordsLinked to original sources
PubMed2006

Annexin-1 downregulation in thyroid cancer correlates to the degree of tumor differentiation.

We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other hand, the most undifferentiated thyroid carcinoma cells (ARO and FRO) presented the lowest level of ANXA1 expression. In surgical tissue specimens from 32 patients with thyroid cancers, we found high immunoreactivity for ANXA1 in papillary (PTC) and follicular (FTC) thyroid cancers while in undifferentiated thyroid cancers (UTC) the expression of the protein was barely detectable. Control thyroid tissue resulted positive for ANXA1. In summary, 70% of UTC examined weakly expressed ANXA1, whereas 65% of PTC or FTC specimens tested showed high expression of the protein. Thus ANXA1 expression may correlate with the tumorigenesis suggesting that the protein may represent an effective differentiation marker in thyroid cancer.

Annexin A1↗
PubMed2006

Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface.

Annexin A1 (ANXA1) has an important role in cell-cell communication in the host defense and neuroendocrine systems. In both systems, its actions are exerted extracellularly via membrane-bound receptors on adjacent sites after translocation of the protein from the cytoplasm to the cell surface of adjacent cells. This study used molecular, microscopic, and pharmacological approaches to explore the mechanisms underlying the cellular exportation of ANXA1 in TtT/GF (pituitary folliculo-stellate) cells. LPS caused serine-phosphorylation of ANXA1 (ANXA1-S27-PO4) and translocation of the phosphorylated protein to the cell membrane. The fundamental requirement of phosphorylation for membrane translocation was confirmed by immunofluorescence microscopy on cells transfected with wild-type or mutated (S27/A) ANXA1 constructs tagged with enhanced green fluorescence protein. The trafficking of ANXA1-S27-PO4 to the cell surface was dependent on PI3-kinase and MAP-kinase. It also required HMG-coenzyme A and myristoylation. The effects of HMG-coenzyme A blockade were overcome by mevalonic acid (the product of HMG-coenzyme A) and farnesyl-pyrophosphate but not by geranyl-geranylpyrophosphate or cholesterol. Together, these results suggest that serine-27 phosphorylation is essential for the translocation of ANXA1 across the cell membrane and also identify a role for isoprenyl lipids. Such lipids could target consensus sequences in ANXA1. Alternatively, they may target other proteins in the signal transduction cascade (e.g., transporters).

Animals↗
PubMed2004

Outcome of children with neuromuscular disease admitted to paediatric intensive care.

AIMS: To determine the outcome of children with neuromuscular disease (NMD) following admission to a tertiary referral paediatric intensive care (PICU). METHODS: All children with chronic NMD whose first PICU admission was between July 1986 and June 2001 were followed up from their first PICU admission to time of study. The outcomes recorded were death in or outside of PICU, duration of PICU admission, artificial ventilation during admission and following discharge from PICU, and readmission to PICU. RESULTS: Over 15 years, 28 children were admitted on 69 occasions. Sixteen (57%) children had more than one admission. The median duration of PICU admission was 4 days (range 0.5-42). Twenty three per cent of unplanned admissions resulted in the commencement of respiratory support that was continued after discharge from the PICU. Severity of functional impairment was not associated with longer duration of stay or higher PRISM scores. Ten children (36%) died, with four (14%) deaths in the PICU. A higher proportion of children with severe limitation of function were among children that died compared to survivors. CONCLUSION: Most children with NMD admitted to the PICU recover and are discharged without the need for prolonged invasive ventilation. However, in this group of children, the use of non-invasive home based ventilation is common and they are likely to require further PICU admission.

Adolescent↗
PubMed2002

A comparison of three scoring systems for mortality risk among retrieved intensive care patients.

AIMS: To assess the impact of two paediatric intensive care unit retrieval teams on the performance of three mortality risk scoring systems: pre-ICU PRISM, PIM, and PRISM II. METHODS: A total of 928 critically ill children retrieved for intensive care from district general hospitals in the south east of England (crude mortality 7.8%) were studied. RESULTS: Risk stratification was similar between the two retrieval teams for scores utilising data primarily prior to ICU admission (pre-ICU PRISM, PIM), despite differences in case mix. The fewer variables required for calculation of PIM resulted in complete data collection in 88% of patients, compared to pre-ICU PRISM (24%) and PRISM II (60%). Overall, all scoring systems discriminated well between survival and non-survival (area under receiver operating characteristic curve 0.83-0.87), with no differences between the two hospitals. There was a tendency towards better discrimination in all scores for children compared to infants and neonates, and a poor discrimination for respiratory disease using pre-ICU PRISM and PRISM II but not PIM. All showed suboptimal calibration, primarily as a consequence of mortality over prediction among the medium (10-30%) mortality risk bands. CONCLUSIONS: PIM appears to offer advantages over the other two scores in terms of being less affected by the retrieval process and easier to collect. Recalibration of all scoring systems is needed.

Child↗
PubMed2002

Use of propofol infusion in Australian and New Zealand paediatric intensive care units.

Despite the risk of propofol infusion syndrome, a rare but often fatal complication of propofol infusion in ventilated children and possibly adults, propofol infusion remains in use in paediatric intensive care units (PICU). This questionnaire study surveys the current pattern of use of this sedative infusion in Australian and New Zealand PICUs. Thirty-three of the 45 paediatric intensive care physicians surveyed (73%), from 12 of the 13 intensive care units, returned completed questionnaires. The majority of practitioners (82%) use propofol infusion in children in PICU, the main indication being for short-term sedation in children requiring procedures. 39% of respondents consider propofol infusion useful in ventilated children requiring longer-term sedation. 67% of paediatric intensivists use maximum infusion doses that may be considered dangerously high (> or = 10 mg/kg/h). Nineteen per cent use propofol infusion for prolonged periods (> 72 hours). A smaller proportion (15%) of respondents indicate that they may use both higher doses and prolonged periods of infusion, a practice likely to lead to a greater chance of serious adverse events. Knowledge of local protocols for the use of propofol infusion is associated with a significantly greater level of monitoring for possible adverse events. We suggest that national guidelines for the use of propofol infusion in children should be developed. These should include clear indications and contraindications to its use, a maximum dose rate and maximum period of infusion, with a ceiling placed on the cumulative dose given and clearly stated minimum monitoring requirements.

Anesthetics, Intravenous↗
PubMed2000

Overexpression of H ferritin and up-regulation of iron regulatory protein genes during differentiation of 3T3-L1 pre-adipocytes.

The role of iron-dependent oxidative metabolism in protecting the oxidable substrates contained in mature adipocytes is still unclear. Because differentiation increases ferritin formation in several cell types, thereby leading to an accumulation of H-rich isoferritins, we investigated whether differentiation affects iron metabolism in 3T3-L1 pre-adipocytes. To this aim, we evaluated the expression of the genes coding for the H and L ferritin subunits and for cytoplasmic iron regulatory protein (IRP) during the differentiation of 3T3-L1 cells in adipocytes induced by the addition of isobutylmethylxanthine, insulin, and dexamethasone. Differentiation enhanced ferritin formation and caused overexpression of the H subunit, thus altering the H/L subunit ratio. Northern blot analysis showed increased levels of H subunit mRNA. A gel retardation assay of cytoplasmic extract from differentiated cells, using an iron-responsive element as a probe, revealed enhanced an RNA binding capacity of IRP1, which correlated with the increase of IRP1 mRNA. The observed correlation between differentiation and iron metabolism in adipocytes suggests that an accumulation of H-rich isoferritin may limit the toxicity of iron in adipose tissue, thus exerting an antioxidant function.

3T3 Cells↗
PubMed2000

Oxalomalate, a competitive inhibitor of aconitase, modulates the RNA-binding activity of iron-regulatory proteins.

We investigated the effect of oxalomalate (OMA, alpha-hydroxy-beta-oxalosuccinic acid), a competitive inhibitor of aconitase, on the RNA-binding activity of the iron-regulatory proteins (IRP1 and IRP2) that control the post-transcriptional expression of various proteins involved in iron metabolism. The RNA-binding activity of IRP was evaluated by electrophoretic mobility-shift assay of cell lysates from 3T3-L1 mouse fibroblasts, SH-SY5Y human cells and mouse livers incubated in vitro with OMA, with and without 2-mercaptoethanol (2-ME). Analogous experiments were performed in vivo by prolonged incubation (72 h) of 3T3-L1 cells with OMA, and by injecting young mice with equimolar concentrations of oxaloacetate and glyoxylate, which are the precursors of OMA synthesis. OMA remarkably decreased the binding activity of IRP1 and, when present, of IRP2, in all samples analysed. In addition, the recovery of IRP1 by 2-ME in the presence of OMA was constantly lower versus control values. These findings suggest that the severe decrease in IRP1 RNA-binding activity depends on: (i) linking of OMA to the active site of aconitase, which prevents the switch to IRP1 and explains resistance to the reducing agents, and (ii) possible interaction of OMA with some functional amino acid residues in IRP that are responsible for binding to the specific mRNA sequences involved in the regulation of iron metabolism.

3T3 Cells↗
PubMed1997

Long-term results of heart valve replacement with bileaflet prostheses.

Bileaflet cardiac prostheses (St. Jude, CarboMedics, Duromedics, Bicarbon, Jyros) have shown a low incidence of complications and good haemodynamic performance. In the last twelve years, 783 bileaflet prostheses were implanted in 690 patients at our Institution. The population of our study comprises 591 bileaflet prostheses (418 CarboMedics, 124 St. Jude, 49 Bicarbon) implanted in the mitral (MVR) (n = 305) or aortic (AVR), (n = 286) position. The follow-up study evaluated 292 male and 295 female patients with age ranging from 13 and 79 years (mean 50.4 +/- 14.7 years). Hospital mortality was 6.6%. Follow-up was 97% complete, with 1822 +/- 33 patient/years and a mean follow-up of 37 months (range 1 to 144 months). Twelve years actuarial freedom from complication according to prosthetic site were calculated as follows (linearized rates in parentheses): late mortality AVR 97.6% +/- 0.6% (2.3%), MVR 96% +/- 0.5% (2.1%); thrombosis AVR 100%, MVR 96% +/- 0.9% (0.8%); embolism AVR 97% +/- 0.5% (1.5%), MVR 96.6% +/- 0.7% (1.8%). Global freedom from anticoagulant-related haemorrhage was 95% +/- 1.2% (2.3%) and 94.5% +/- 0.7% (2.2%) following AVR, 94 +/- 0.6% (2.1%) following MVR. The difference of the haemorrhagic risk for prosthetic site was not significant (p > 0.05). Functional improvement was confirmed by the low postoperative NYHA functional class. According to our results, cumulative experience with bileaflet valves has shown very good long-term results in term of low rate of complication, long-term survival and quality of life.

Actuarial Analysis↗
PubMed1996

Submitral left ventricular aneurysm. Report of 2 surgical cases.

Submitral left ventricular aneurysm most commonly occurs among the black population. Nevertheless, this lesion has been described among whites. We report 2 cases of submitral left ventricular aneurysm that we treated successfully by surgery. Case 1 is that of a 52-year-old Brazilian black man with a submitral left aneurysm and mitral incompetence. Case 2 is that of a 25-year-old white man with a history of recurrent stroke; his echocardiographic study showed a small submitral left ventricular aneurysm. Due to the growing incidence of submitral left ventricular aneurysm among the white population, we emphasize the importance of a targeted echocardiographic study in all patients with a history of embolic episodes in the absence of apparent risk factors for embolism.

Adult↗
PubMed1996

[A case of Veratrum poisoning].

A poisoning from a Veratrum album infusion mistaken for Gentiana lutea is described. Confusion between these two plants can easily occur because they are very similar, although flowers and disposition of leaves allow their botanic determinat: V. album leaves are alternate and flowers are white, while G. lutea leaves are opposite and flowers yellow. The poisoning involves gastrointestinal (pyrosis, vomiting) and cardiocirculatory systems (bradyarrhy-thmias, A-V dissociation, vasodilatation) Atropine is the drug of choice.

Humans↗
PubMed1995

Stentless fresh pulmonary homograft in mitral position.

We report the implantation of a fresh, stentless pulmonary homograft in the mitral position as an attempt to treat the 2nd recurrence of prosthetic endocarditis in a 66-year-old man. The postoperative course was uneventful; early postoperative transesophageal echocardiography showed a competent valve with a gradient of 4.2 mmHg. Fifteen months postoperatively, transthoracic echocardiography showed a good functioning homograft with a competent valve and no recurrence of endocarditis.

Aged↗
PubMed1994

Prosthetic valve obstruction: thrombolysis versus operation.

An acute obstruction is a life-threatening complication of mechanical valve prostheses, and is caused by the formation of fresh clot or fibrous tissue overgrowth, or both. Accurate selection of the most appropriate treatment for a particular patient is mandatory. From January 1991 to July 1992, 28 cases of prosthetic thrombosis were managed. Twenty patients underwent surgical treatment, with one operative death, and 8 patients were treated with thrombolysis using recombinant tissue-type plasminogen activator (rt-PA). The criteria for using thrombolysis were (1) the recent onset of symptoms, (2) transesophageal echocardiographic evidence of clots on the valve or cardiac chambers, and (3) preserved disc excursions. All patients who underwent thrombolysis had mechanical valves (two bileaflets, four tilting discs, and two ball valves); seven valves were in the mitral position and one was in the aortic. Symptoms of obstruction consisted of cardiac failure in 6 cases or thromboembolism in 5, or both. The mean interval between the onset of symptoms and the initiation of thrombolysis was 81 +/- 65 hours. After infusion of the rt-PA, normal valve function was restored in all patients, as documented by transesophageal echocardiography. No deaths or neurologic complications occurred; there was one episode of minor peripheral embolism. Thrombolysis using rt-PA may be the appropriate treatment in patients with primary thrombosis of mechanical valves, thereby avoiding the operation-related risks.

Adult↗
PubMed1994

Acute postoperative block of mechanical prostheses: incidence and treatment.

Acute intermittent postoperative block of mechanical prostheses is a rare and life-threatening complication; its incidence and treatment are not well defined. Between January 1975 and June 1991, 2839 mechanical prostheses were implanted using the same technique: mattress suture for mitral valve replacement and simple suture for aortic valve replacement. Prosthetic block occurred in eight patients: four following mitral valve replacement and four after aortic valve replacement. The blocked prosthesis was always a tilting disc valve (five Sorin, two Björk-Shiley and one Medtronic). The event occurred over a time interval of 6-48 h (mean(s.d.) 17.3 (15.6)h). All patients having mitral valve replacement needed emergency prosthetic replacement. In aortic valve replacement, reoperation was necessary in two patients; the disc block disappeared in the others. All patients are alive with a follow-up ranging between 3 and 168 (mean 32.5) months. No structural failure was found in explanted prostheses leading to a diagnosis of extrinsic block. The overall incidence of this complication was 0.28% (eight of 2839); 0.24% (four of 1645) for mitral valve replacement and 0.33% (four of 1194) for aortic valve replacement respectively (n.s.). It was exclusively related to tilting disc valves (0.44%; eight of 1830) versus ball and bileaflets valve (0 of 1009). In mitral valve replacement reoperation on patients is mandatory; in aortic valve replacement patients the left ventricular pressure itself can overcome the prosthetic block. Attention should be paid to valve excision and suture techniques as tilting disc prostheses are more vulnerable to extrinsic block. Furthermore, their use is contraindicated in redo operations and mitral valve replacement with total or partial preservation of mitral apparatus.

Adult↗