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Biomedical subjects

G Distefano

Publications and source records attributed to G Distefano.

At least 19 recordsLinked to original sources

Troponin I as a biomarker of cardiac injury in neonates with idiopathic respiratory distress.

Troponin I (TnI), an inhibitory protein complex located on the actin filament of cardiac muscle, has become a specific marker of myocardial damage. Troponin has been studied in a wide range of clinical settings. However, many questions are still unanswered, especially in preterm neonates with the most common pathology at birth, such as idiopathic respiratory distress syndrome (IRDS). The aim of this study was to establish a reference range for cardiac TnI for healthy preterm infants and serum levels in sick preterm infants with IRDS. Echocardiography was performed and TnI serum levels were measured at a median age of 62 hours of life in three groups of healthy preterm infants (n = 10), and ventilated infants with moderate (n = 15) and severe IRDS (n = 15). Ventilated infants with idiopathic moderate IRDS had significantly different cardiac parameters (R/L ejection fraction, R/L stroke volume, R/L cardiac output; p < 0.05) and significantly higher cardiac TnI levels than healthy infants (0.037 versus 0.01 microg/mL; p < 0.05). Furthermore, infants with severe IRDS had higher TnI concentrations than infants with moderate IRDS (0.26 versus 0.037 microg/mL; p < 0.05). The results of this study show that increased TnI serum levels in sick preterm infants with IRDS are explained by myocardial injury or dysfunction due to impaired arterial oxygenation or reduction in cardiac output during treatment with mechanical ventilation. These results suggest that cardiac TnI may be a useful, specific marker for myocardial damage in preterm neonates with IRDS.

Biomarkers↗

[The pharmacological manipulation of Botallo's duct in the duct-dependent congenital cardiopathies and in the preterm infants with respiratory distress. A review and personal findings].

Botallo's duct connects the systemic and pulmonary circulation. It can play a crucial hemodynamic role in some cardiac and respiratory diseases of the newborn, and strongly influences the outcome if it remains patent after birth or if it closes rapidly. The recently acquired in-depth knowledge on the genesis of these events have advanced the so called ''pharmacological manipulation of Botallo's duct'', i.e. pharmacological treatment to regulate the opening or closure of the ductus depending on clinical requirements and that, as will be described, is a key issue in managing newborns with severe cardiac and/or respiratory distress. This study illustrates the main underlying mechanisms of duct patency during intrauterine life and its closure after birth, and then describes the clinical conditions of the newborn where Botallo's duct must be kept patent after birth (duct-dependent cardiac malformations) and where its closure must be accelerated (patent duct associated idiopathic respiratory syndrome). It also reports the recent findings on the use of prostaglandins (PGE1) and prostaglandin synthesis inhibitors (indomethacin, ibuprofen) and the potential use of drugs capable of favouring or inhibiting nitric oxide in the duct endothelium.

Alprostadil↗

[Cerebral venous sinuses thrombosis in an infant with supramitral obstructive membrane associated with partial anomalous pulmonary venous return].

Cerebral venous thrombosis is quite rare in newborn infants, but probably its incidence is not well evaluated because clinical signs and cerebral echocardiography are not specific. We report the case of an newborn infant with massive cerebral venous thrombosis associated with heart malformation: supramitral ring and partial anomalous pulmonary venous connection in the superior vena cava.

Adolescent↗

[Transient right ventricular hypertrophy in a newborn infant exposed in utero to nimesulide].

The use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy has been sometimes related to harmful cardiac effects secondary to the precocious closure in uterus of ductus arteriosus. This closure is linked to the inhibition of the cyclo-oxygenase (COX) enzyme that plays a key-role in the prostaglandin synthesis. Recently, it has been acquired that, among NSAIDs, nimesulide has a more selective action on the isoform COX-2 that is more strictly related to inflammatory phenomena. The isoform COX-1, instead, steadily expressed in tissues, would be responsible of continuous prostaglandin synthesis maintaining patent the ductus arteriosus in uterus. The case reported in this paper describes a remarkable right ventricle hypertrophy observed in a newborn whose mother, during the whole period of pregnancy, frequently used nimesulide as analgesic. Probably, in spite of its selective action on COX-2, the prolonged use of nimesulide has determined a closure of the ductus, inducing a functional fetal pulmonary hypertension that resolved after birth with the consequent regression of the right ventricular hypertrophy.

Anti-Inflammatory Agents, Non-Steroidal↗

Procalcitonin serum levels in perinatal bacterial and fungal infection of preterm infants.

AIM: To determine reference values for procalcitonin (PCT) and C-reactive protein (CRP) for gestational age and to use these parameters as diagnostic markers of perinatal bacterial and fungal infection. METHODS: PCT and CRP serum levels were measured in a case-control study in a group of 35 low birthweight infants (< 34 wk of gestation). 27 babies (77%) had clinical signs of infection confirmed by positive blood cultures and were compared to 8 (23%) uninfected matched patients. Seventeen (63%) of them had bacterial infection and 10 (37%) had fungal infection (Candida). Serum PCT (Brahms Diagnostika) and CRP (Immunoassay Vitros 950) were measured serially at 3, 7 and 10d of life. RESULTS: At any time, PCT and CRP levels were significantly higher in neonates with perinatal infection (p < 0.05) (> 0.7 ng ml(-1) and > 1 mg dl(-1) respectively). PCT showed a more rapid response to infection (9.3 +/- 1.5 ng ml(-1)). especially to bacterial infection (10.8 +/- 1.4 ng ml(-1)), than CRP (1.5 +/- 0.5 mg dl(-1)) (sensitivity 99% vs 88%). Lower sensitivity was noted for both parameters. PCT and CRP, to follow babies with fungal infection (6.7 +/- 0.8 ng ml(-1) and 0.9 +/- 0.7 mg dl(-1), respectively) (sensitivity 77% vs 58%). CONCLUSION: This study gives PCT reference values in preterm babies with perinatal infection. In these babies, PCT seems to be more sensitive than CRP as a diagnostic marker of infection. Both parameters can be used alone or in combination for a better identification and follow-up of bacterial and fungal infection during the perinatal period.

Bacterial Infections↗

Unilateral supraorbital keyhole approach in patients with middle cerebral artery (M1-M2 segment) symmetrical aneurysms.

A left middle cerebral artery aneurysm at the bifurcation (M1-M2 segment) and a right smaller aneurysm, symmetrical to the previous one were diagnosed in a 69-year-old female after angiographic examination for subarachnoid hemorrhage. The preoperative radiological study did not enable us to identify the bleeding aneurysm so a left supraorbital keyhole approach was performed to operate on the bigger aneurysm. In the same surgical session, using the same way of approach, we decided to attack also the right aneurysm which then revealed itself as being responsible for bleeding. The postoperative angiograms confirmed the complete exclusion of both aneurysms and the patient was discharged after good recovery. Although there are remarkable controversies about the surgical strategies for multiple aneurysms, our experience gives us the opportunity to emphasize the supraorbital keyhole approach and to reconsider the "timing" of multiple/bilateral aneurysms.

Aged↗

[The newborn with cardiological problems. The dilemma between malformative and non-malformative pathology].

Cardiovascular impairment is frequent during the neonatal period and can be expression of malformative or not-malformative pathology. In both conditions the clinical presentation is often dramatic with cyanosis and/or heart failure. The neonatologist has to make differential diagnosis as soon as possible, because cardiac malformations in the neonatal period are usually ductus arteriosus-dependent and can worsen suddenly after its closure. Since colour Doppler-echocardiography is not available in all the neonatal units in order to be helped in the diagnosis, it is very important that neonatologists learn to use the indications obtained with a careful physical examination and with some simple instrumental tests, as chest X-ray, electrocardiogram and blood gas analysis. In this article a review is made of the most frequent heart malformations associated with cyanosis and/or heart failure during the neonatal period (complete transposition of the great arteries, Fallot's tetralogy, tricuspid and pulmonary atresia, aortic coarctation, interventricular septal defect, persistence of ductus arteriosus) and the most common neonatal pathologic conditions simulating congenital heart diseases (persistence of fetal circulation, neonatal transitory myocardial ischemia, hypervolemia, hypoglycemia, hypocalcemia). Some clinical, instrumental and laboratory findings that could be useful for the diagnosis in absence of echocardiography are also reported.

Cyanosis↗

Serial protein S-100 serum levels in preterm babies with perinatal asphyxia and periventricular white matter lesions.

In the last years new diagnostic technologies were developed to assess brain development and to identify early brain injury. Some of them are very attractive methods but invasive, expensive, and time-consuming. The availability of clinically useful serum markers of risk for perinatal brain damage will easily permit the development of rational strategies for prevention of cerebral insults in neonates and more accurate prognostic counseling. In this study, protein S-100 (PS-100), a cytosolic constituent of neuroglial cells, was measured serially, during the neonatal period, in a group of preterm infants suffering perinatal asphyxia. Protein S-100 was measured at 1, 7, and 21 days of life by radioimmunoassay. Cerebral ultrasound confirmed cerebral white matter insult. The results of this study show significantly higher protein S-100 serum levels in asphyxiated preterm babies with periventricular white matter lesions, with a peak at 24 hours of life (5.7 +/- 2.9 microg/L) compared with healthy preterm babies (0.6 +/- 0.3 microg/L) ( p <0.05) and progressively lower values at seven (3.3 +/- 2.4 microg/L) and 21 days (2.2 +/- 1.3 microg/L) of life ( p <0.05). These data suggest that elevated protein S-100 serum levels can be considered an indicator of regional brain damage in preterm infants, allowing noninvasive, superior scrutiny of perinatal asphyxia and potential early preventive strategies.

Analysis of Variance↗

[Cardiac involvement in Kawasaki disease. Our experience].

BACKGROUND: Kawasaki disease is an acute vasculitis of unknown cause that affects children under 5 years of age and in 20-25% of cases can cause coronary artery anomalies. Early therapy with intravenous gamma globulin and aspirin greatly decreases the risk of developing coronary anomalies, but sometimes coronary disease develops even in timely diagnosed and treated cases. METHODS: Personal experience in 41 children with Kawasaki disease is reported. Age was within three months and 5 years. All patients had electrocardiography and echocardiography at diagnosis, after 1 week, at the third, sixth, and eighth week, after six months and after 1 year from diagnosis. Echocardiographic cardiac anomalies were found only in 5 cases (12.19%). Average age in these cases was lower. RESULTS: In these cases coronary involvement developed in spite of early diagnosis and therapy (intravenous gamma globulin 400 mg/kg die and aspirin) electrocardiographic findings were not relevant or specific to coronary arteries anomaly. In three cases coronary anomalies regressed during the first year from diagnosis, the other two are still in the first year of follow-up. Nine children had a long term follow-up (6 to 9 years) and they were all normal except one with renal arteritis and another with slight mitral incompetence. CONCLUSIONS: The authors underline the role of clinical and instrumental follow-up that should be extended to all patients affected by Kawasaki disease with coronary anomalies even if early regressed.

Age Factors↗

A new Chinese hamster ovary cell line expressing alpha2,6-sialyltransferase used as universal host for the production of human-like sialylated recombinant glycoproteins.

Chinese hamster ovary (CHO) cells are widely employed to produce glycosylated recombinant proteins. Our group as well as others have demonstrated that the sialylation defect of CHO cells can be corrected by transfecting the alpha2,6-sialyltransferase (alpha2,6-ST) cDNA. Glycoproteins produced by such CHO cells display both alpha2,6- and alpha2,3-linked terminal sialic acid residues, similar to human glycoproteins. Here, we have established a CHO cell line stably expressing alpha2,6-ST, providing a universal host for further transfections of human genes. Several relevant parameters of the universal host cell line were studied, demonstrating that the alpha2,6-ST transgene was stably integrated into the CHO cell genome, that transgene expression was stable in the absence of selective pressure, that the recombinant sialyltransferase was correctly localized in the Golgi and, finally, that the bioreactor growth parameters of the universal host were comparable to those of the parental cell line. A second step consisted in the stable transfection into the universal host of cDNAs for human glycoproteins of therapeutic interest, i.e. interferon-gamma and the tissue inhibitor of metalloproteinases-1. Interferon-gamma purified from the universal host carried 40.4% alpha2,6- and 59.6% alpha2,3-sialic acid residues and showed improved pharmacokinetics in clearance studies when compared to interferon-gamma produced by normal CHO cells.

Animals↗

Usefulness of platelet glycoprotein IIb/IIIa inhibitors in coronary stenting for reconstruction of complex lesions: procedural and 30 day outcome.

BACKGROUND: Intracoronary stent implantation during percutaneous transluminal coronary angioplasty (PTCA) has shown favorable results, reducing acute complications associated with PTCA, such as coronary artery dissection and abrupt or threatened vessel closure. However, treatment of lesions with a complex morphology and diffuse disease, requiring long or multiple coronary stents, is still associated with a poorer outcome. We investigated the hypothesis that abciximab might lead to a different outcome in patients with complex coronary lesions, which require long or multiple stent implantation. METHODS: One hundred and six patients were randomized to receive either a combination of abciximab (bolus and 12 hour infusion) and weight-adjusted low-dose heparin or weight-adjusted heparin alone and followed up to 30 days. RESULTS: The procedural success rate was 100% in both groups of patients. In the control group a composite rate of major adverse events such as any death irrespective of cause, Q wave or non-Q wave myocardial infarction, acute or subacute stent thrombosis and urgent revascularization of 15.3% was shown at 30-day follow-up. The use of abciximab reduced the composite adverse event rate to 3.7% (76% absolute reduction, p < 0.05). CONCLUSIONS: The use of abciximab during high risk stenting is safe and reduces the risk of cardiac events at 30-day follow-up as compared to standard treatment with heparin. A longer follow-up period is warranted to confirm the beneficial effects observed at 30 days with abciximab in this setting.

Abciximab↗

Management of chronic subdural hematoma in patients treated with anticoagulation.

BACKGROUND: The diffusion of the surgical technique of cardiac valve replacement with metallic prostheses, as well as bypass graft in the arterial occlusive disease of the lower extremities, both requiring permanent oral anticoagulation, has increased the number of patients affected by chronic subdural hematoma that can be diagnosed at an earlier stage of this disease with the advent of the CT. METHODS: The records of seven patients with mean GCS = 14.2 and mean clinical grade = 1.85 affected by chronic subdural hematoma and in treatment with anticoagulants were examined retrospectively. All the patients underwent subtemporal craniectomy plus closed drainage or burrhole(s) plus closed drainage after immediate correction of hypocoagulability by administration of vitamin K and fresh frozen plasma and normalization of PA by calcium heparin. RESULTS: Outcome was good for all the patients except one who died because of cerebral herniation due to massive solid subdural hematoma during extracorporeal dialysis. Complications included: intracerebral hemorrhage, solid subdural hematoma, slow brain reexpansion, subdural collection reaccumulation and cerebral embolism. Three patients required re-operation. Mean duration of hospital stay was 18 days with range from 7 to 24 days. CONCLUSIONS: Basing on this retrospective study and the proposed pathophysiology, the guidelines for optimal management of this subgroup of patients are proposed. Recommendations include the immediate correction of hypocoagulability, the appropriate surgical technique and the cautious conversion to oral anticoagulation as well as the appropriate timing of such conversion.

Aged↗

Thrombomodulin serum levels in ventilated preterm babies with respiratory distress syndrome.

UNLABELLED: A soluble form of thrombomodulin (TM), an anticoagulant proteoglycan of the endothelial cell membrane, considered a marker of vascular endothelial damage, was measured in plasma of preterm infants with respiratory distress syndrome (RDS). In these patients, lung immaturity leads to endothelial leak of plasma proteins and to surfactant inhibition. In 18 babies with RDS, plasma TM concentration was significantly elevated compared with values of a matched group of babies without pulmonary disease (276.1 ng/ml vs 141.3 ng/ml) (P < 0.05). Furthermore, TM levels of mechanical ventilated babies (IPPV) with severe RDS were higher than those of babies with moderate RDS and treated with nasal CPAP (340.9 ng/ml vs 174.2 ng/ml) (P < 0.05). CONCLUSION: These data show that TM can be used as marker of pulmonary endothelial damage in preterm babies treated with mechanical ventilation for RDS and suggest early intervention with exogenous surfactant to limit alveolar protein leakage and surfactant inactivation.

Blood-Air Barrier↗

Traumatic chronic subdural hematoma over 80 years. A preliminary prospective study.

Six very elderly patients (mean of age: 85 years with range from 80 to 95 years) with mean GCS = 12 and mean clinical grade = 2.5 affected by traumatic chronic subdural hematoma (CT mean maximum thickness = 2.8 +/- 0.46 cm with midline shift = 1.56 +/- 0.48 cm and absence of homolateral mesencefalic cistern in all case but one) underwent parietal or frontal craniectomy under temporalis muscle and 48-h closed subdural drain. There was no mortality as consequence of the operative procedure. In all the patients but one who died postoperatively from a preoperative midbrain infarction secondary to a transtentorial herniation, there was a progressive and slow clinical improvement in spite of residual markedly persistent fluid collection (CT mean maximum thickness 1.44 +/- 0.19 cm) with mass effect (CT mean midline shift = 0.5 +/- 0.17 cm) due to a some failure of the brain to re-expand. Impairment of hemodynamic reserve should be considered as important cause of failure of the brain re-expansion. Clinical and CT control within two months after discharge from hospital demonstrated further clinical improvement (mean GOS = 4.6) and resolution of subdural residual fluid collection. Basing on these results we recommend do not reoperate persistent subdural fluid collection if there is clinical improvement. The patient can be discharged from hospital or transferred to Geriatric Department where he can be clinically and CT evaluated. Only a clinical deterioration or an increase of residual subdural fluid collection provides clear indication to reoperative surgery.

Aged↗

"HepG2/erythroid/brain" type glucose transporter (GLUT1) is highly expressed in human epidermis: keratinocyte differentiation affects GLUT1 levels in reconstituted epidermis.

In mature animals, the "HepG2/erythroid/brain" glucose transporter isoform (GLUT1) appears to be expressed at the highest levels at blood tissue barriers; however, these levels may still be lower than the levels of expression seen in fetal tissues. Also, glucose transporters might serve as water channels. Therefore, we decided to investigate GLUT1 expression in human epidermis, a very active tissue, in terms of metabolism, even if not directly vascularized. We found GLUT1 transcripts in human skin and demonstrated, by immunohistochemistry, that GLUT1 protein is highly expressed in the basal layer and, to a lower extent, in the immediately suprabasal layer of the epidermis. This distribution pattern suggested that GLUT1 expression is affected by keratinocyte differentiation. To investigate this possibility, we used human epidermis reconstituted in culture. Our culture system allows the reconstruction of a stratified squamous epithelium which has been successfully grafted onto patients presenting large skin defects. Human keratinocytes have been cultured under conditions which allow a modulation of cellular differentiation and stratification. We observed that (i) GLUT1 expression is 4-6-fold higher in "stem-like" basal cells than in large, differentiated keratinocytes; (ii) culture conditions causing cell differentiation reduce GLUT1 expression, while conditions which minimize either differentiation or stratification of keratinocytes enhance GLUT1 expression. Finally, we found that IGF-1 and insulin, probably acting through the IGF-1 receptor, increase GLUT1 expression and stimulate glucose transport activity in epidermis reconstituted in culture. In conclusion, our data demonstrate that GLUT1 is highly expressed in the basal layers of human epidermis and that its expression is modulated by keratinocyte differentiation.

Brain↗

Familial Jarcho-Levin syndrome.

Jarcho-Levin syndrome is a variety of autosomal recessive spondylocostal dysostosis characterized by severe deformity of the thoracic cage, leading to respiratory failure and early death. There are often associated dysmorphic features. The disease is more frequent in Puerto Ricans and rare in Europe. A Sicilian family with four affected individuals in two interrelated sibships is reported.

Abnormalities, Multiple↗

Autosomal dominant atrial septal defect of ostium secundum type. Report of three families.

The authors report on three Sicilian families with 17 individuals (10 females and 7 males) in successive generations affected by atrial septal defect of ostium secundum type (S-ASD) without conduction defect. The anomaly was inherited as an autosomal dominant trait. Cytoplasmic inheritance could be excluded, the anomaly being transmitted also by fathers. Familial S-ASD is probably more frequent than commonly reported since cardiological examination of the relatives is not routinely performed in every case of apparently sporadic ASD.

Adult↗