Search PubMed⌕ Search

Biomedical subjects

E Rossi

Publications and source records attributed to E Rossi.

At least 145 records · Page 8Linked to original sources

Direct resolution, characterization, and stereospecific binding properties of an atropisomeric 1,4-benzodiazepine.

The chromatographic resolution of 7-chloro-1,3-dihydro-1-(1,1-dimethylethyl)-5- (2-fluorophenyl)-2H-1,4-benzodiazepin-2-on (7), the 2'-fluoro, N1-tertbutyl analogue of diazepam, was attained on both analytical and preparative (mgs) scales, by using several chiral stationary phases (CSPs). The stereochemistry of this compound was characterized by means of 1H-NMR Nuclear Overhauser Effect (NOE) analysis. The single enantiomers of 7 were tested for their configuration and stereochemical stability by circular dichroism (CD), and their interaction with the central nervous system (CNS) benzodiazepine receptor was assayed, showing a significant difference in their binding affinities. Protein binding studies with human serum albumin (HSA, the main benzodiazepine carrier in human plasma) immobilized on a silica stationary phase revealed that HSA also preferentially binds one stereoisomer of 7. However, both on line CD detection and stereospecific interaction with other common drugs clearly demonstrated that the stereoselectivity of immobilized HSA for 7 is opposite to that for all the other studied benzodiazepines. In addition, HSA stereoselectivity for 7 is opposite to CNS receptor binding stereoselectivity for the same compound. Such HSA anomalous stereoselectivity for 7 was also confirmed in aqueous buffer solution by competitive displacement studies. Compared to other chiral 1,4-benzodiazepines, compound 7 thus shows several anomalous binding properties: HSA and the CNS receptor demonstrated opposite enantioselective discrimination; HSA has reversed enantioselectivity for compound 7; and HSA stereospecifically binds the low-affinity enantiomer.

Benzodiazepines↗

Impaired counterregulatory hormonal and metabolic response to exhaustive exercise in obese subjects.

A reduction of postprandial thermogenesis has been described in obesity; insulin resistance and/or decreased sympathetic nervous system activity seem to play the major role in its pathogenesis. On the other hand, a normal energy expenditure during exercise has been reported. At present, the response and the role of catecholamines in energy metabolism during exercise in obesity have not been well clarified yet. The aim of this work was to study the metabolic and hormonal changes caused by intense exercise in obesity. Nine obese subjects and ten normal weight controls were submitted to exhaustive exercise on a cycloergometer. Blood glucose, free fatty acids (FFA), glycerol, lactate, beta-OH-butyrate, insulin, glucagon, plasma growth hormone (HGH), catecholamine plasma levels were assayed before and at the end of exercise, and after a recovery period. The energy cost of exercise was evaluated by indirect calorimetry. In our experiment muscular exercise did not provoke any change in blood glucose and FFA plasma levels in either of our groups. In the obese subjects the insulin plasma levels were higher than in the controls. Glucagon plasma levels did not change. The exercise responses of norepinephrine (NE) (4.28 +/- 0.74 vs 8.81 +/- 1.35 nmol/l; P < 0.01), epinephrine (E) (234.21 +/- 64.18 vs 560.51 +/- 83.38 pmol/l; P < 0.01) and plasma growth hormone (HGH) (134.84 +/- 58.97 vs 825.92 +/- 195.25 pmol/l; P < 0.01) were significantly lower in obese subjects. At the end of exercise, the thermic effect of exercise did not differ between obese and control subjects (0.335 +/- 0.038 vs 0.425 +/- 0.040 kJ/min x kg fat-free mass. Our findings indicate that an impaired counterregulatory hormone response to exercise exists in obese subjects. The thermic effect of exercise does not seem to be affected by either the reduced catecholamine response nor insulin resistance.

Adult↗

Contractile reserve of dysfunctional myocardium after revascularization: a dobutamine stress echocardiography study.

OBJECTIVES: We sought to investigate the effects of revascularization on the contractile reserve of dysfunctional myocardium. BACKGROUND: The improvement in dysfunctional but viable myocardium after revascularization is frequently less than expected from the amount of contractile reserve detected on dobutamine stress echocardiography. The fate of the contractile reserve, when it does not result in an adequate contractile recovery, is unknown. METHODS: Basal contraction and contractile reserve of infarct zones were assessed by dobutamine stress echocardiography in 21 postinfarction male patients before and > 3 months after revascularization (30 infarct zones; mean +/- SD left ventricular ejection fraction 35 +/- 8%). An infarct zone wall motion score index (WMSI) was calculated. RESULTS: Before revascularization, contractile reserve was present in 14 infarct zones (12 patients) and absent in 16 (9 patients). After revascularization, ejection fraction increased by 5 +/- 4% (p < 0.01) in patients classified as positive for contractile reserve and remained unchanged in those classified as negative. New York Heart Association classification improved in 58.3% and 22.2% of patients, respectively. Basal contraction improved in eight zones with previous contractile reserve (57.1%) and in one zone without (6.3%) (p < 0.01). Contractile reserve was still evident in 13 zones with previous contractile reserve (93%; 8 with contractile recovery), and it developed in 6 zones without (38%; none with contractile recovery). WMSI values after revascularization were decreased from values before revascularization during low dose dobutamine in zones with and without previous contractile reserve (p < 0.01 and < 0.05, respectively). CONCLUSIONS: After revascularization, contractile reserve is maintained or even increases in viable infarct zones that do not recover as expected. It may also develop in some infarct zones judged not to be viable before revascularization. This increased contractile reserve may play a role in the functional improvement of patients after revascularization.

Aged↗

CD36 autoantibodies and thrombotic diathesis, thrombocytopenia and repeated early fetal losses.

BACKGROUND AND OBJECTIVES: Autoantibodies to CD36, a platelet glycoprotein, have been found in patients with thrombotic thrombocytopenic purpura, and in those with lupus-like anticoagulant with thrombotic complications. MATERIALS AND METHODS: Conventional hematologic and laboratory methods were used. The patient was a pregnant woman, who had had two early fetal losses separated by a normal offspring. Despite severe thrombocytopenia, she was asymptomatic. RESULTS: Serological investigations were strongly suggestive of CD36 autoantibodies. Neither clinical nor laboratory data were typical of those usually associated with cd36 autoantibodies, namely thrombotic thrombocytopenic purpura (TTP), systemic lupus erythematosis (SLE), or prothrombotic compliance. Prophylaxis with salicylates and prednisone was started at the 8th week of gestation, and an offspring with mild thrombocytopenia was delivered by cesarean section at the 32nd week of gestation because of abruptio placentae. CONCLUSIONS: There may be a cause-and-effect relationship between early fetal losses and CD36 autoantibodies.

Abortion, Habitual↗

Endothelial cell-associated tissue factor pathway inhibitor (TFPI) antigen in severe nondiabetic obese patients: effect of hyperinsulinemia.

It has been suggested that the extrinsic coagulation system plays a crucial role in the initiation of blood coagulation in atherosclerotic disease and that TFPI, the inhibitor of the factor VIIa/tissue factor complex, bound to the endothelial cells, could prevent in vivo blood clotting. Because obesity has a role in the pathogenesis of atherosclerotic cardiovascular disease, we measured TFPI antigen plasma levels (ng/mL) by ELISA at baseline and 5 minutes after an IV bolus of 20 IU/kg body weight of unfractionated commercial mucous heparin in 12 obese patients with a mean body mass index (BMI) of 41.4 +/- 1.4 kg/m2 and 14 normal-weight control subjects (BMI 23.1 +/- 1.3 kg/m2). All subjects were submitted to an OGTT. The obese patients displayed a normal glucose tolerance. However, they had a different glucose-induced hyperinsulinemia (14.9 +/- 2.0 versus 7.8 +/- 0.8 mU/L, p < 0.01). Total serum cholesterol did not differ between controls and obese patients, whereas plasma triglycerides were higher in the latter group. Basal TFPI antigen plasma levels were similar in obese and controls (83.8 +/- 5.0 versus 77.7 +/- 3.5 ng/mL, p = N.S.). In contrast, after heparin a significantly lower rise in TFPI antigen plasma levels was observed in obese patients (511.2 +/- 43.4 ng/mL) (p < 0.003). Moreover, a significant inverse correlation was found between the heparin-stimulated TFPI antigen plasma levels and both BMI and basal plasma insulin concentrations. Thus, the link between insulin level and endothelial cell-associated TFPI could at least partially explain why obese patients are more prone to develop cardiovascular disorders.

Adult↗

Thyroid function in a population of children with attention deficit hyperactivity disorder.

OBJECTIVE: To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated. METHOD: Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed. RESULTS: The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%. CONCLUSION: Routine thyroid hormone screening is not indicated in children with non-familial ADHD.

Adolescent↗

Implant-retained mandibular overdentures with immediate loading. A retrospective multicenter study on 226 consecutive cases.

A multicenter retrospective study has been conducted on 226 patients necessitating an implant-supported overdenture in the lower jaw. The patients were provided with 904 osseointegrated implants inserted in the interforaminal area of the mental symphisis (4 implants per patient). 4 titanium implant systems were used: TPS and ITI screw implants (Straumann Institute, Waldenburg, Switzerland); Ha-Ti screw implants (Mathys Dental Implants, Bettlach, Switzerland); NLS screw implants (Friatec, Mannheim, Germany). Immediately after implant placement, a U-shaped gold bar was fabricated and implants were immediately loaded with an implant-retained overdenture. Out of 226 patients treated, 194 were followed from a minimum of 2 years to a maximum of 13 years, with a mean follow-up of 6.4 years, whereas 32 patients dropped out during follow-up. The overall failure rate of implants was 3.1% (24/776 implants), whereas the failure rate of bars was 1.5% (3/194 bars). Results from this study showed that the success rate of immediately loaded implants is similar to that obtained in the case of delayed loading, after osseointegration has taken place. In contrast, this method shortens dental rehabilitation times with relevant satisfaction for patients.

Adult↗

Mobilization/transplantation of peripheral blood progenitor cells for aggressive non-Hodgkin's lymphoma with marrow involvement.

Thirty-five aggressive non-Hodgkin's lymphomas (NHL) with marrow involvement received high-dose cyclophosphamide (7 g/m2) and G-CSF in order to collect peripheral blood progenitor cells (PBPC). Fourteen patients were in partial remission, 16 patients were in relapse ("sensitive", 12; "resistant", 4) and 5 patients were in refractory to conventional treatment. A good yield of PBPC was obtained in 30 patients, while a low number of CD34+ cells and of CFU-GM was seen in two cases. Two patients entered progression and one patient died. Thirty patients underwent PBPC autografting. Twenty-nine out of 35 (83%) patients entered complete remission (CR). Two patients died in CR of infection following marrow aplasia 3 and 6 months after autografting. At 3 years the probability of survival and disease-free survival (DFS) are of 62% and 51% respectively.

Adolescent↗

Ongoing prothrombotic state in the portal circulation of cirrhotic patients.

Portal thrombosis may complicate the clinical course of cirrhosis, but the pathophysiologic mechanism is unclear. Aim of the study was to evaluate the behavior of clotting system and endotoxemia in portal vein and in peripheral circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt (TIPS). Portal blood showed higher values of F1 + 2 [Median (range): 2.5 (1.1-5.3) vs. 1.1 (0.6-2.1) nM, p < 0.01], D-dimer [765 (184-1713) vs. 192 (64-813) ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p < 0.01] than peripheral circulation. In the portal vein, all but one sample had F1 + 2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper limit of control values). Fibrinogen was lower in the portal circulation compared to peripheral circulation but the difference was not significant [85 (58-195) vs. 134 (75-244) mg/dl, p > 0.05]. Endotoxemia was directly correlated with F1 + 2 (Rho = 0.92 p < 0.006) and D-dimer (Rho = 0.93, p < 0.005). This study shows that an ongoing prothrombotic state is present in the portal circulation of cirrhotic patients and may play a pivotal role in the thrombotic episodes occurring in this clinical setting.

Adult↗

Frequency and distribution of herpesvirus-like DNA sequences (KSHV) in different stages of classic Kaposi's sarcoma and in normal tissues from an Italian population.

The frequency and distribution of herpesvirus-like DNA sequences (KSHV) were investigated by PCR in the pathologic skin lesions of a series of 22 HIV-negative elderly patients with classic Kaposi's sarcoma (KS) from Italy, one of the few regions of the world where classic KS is prevalent. Viral sequences were clearly identifiable in 15 cases, in particular in 2 of 5 patch, in 3 of 6 plaque and in 10 of 11 nodular lesions. Our findings confirm the association of these herpesvirus-like DNA sequences with KS in unrelated populations, providing evidence of the putative KS-associated agent in all different histologic lesions of the disease, mainly in the nodular stage. The search for other herpesviruses by PCR showed that Epstein-Barr virus (EBV) sequences were present in 7 of 22 pathologic skin lesions. In 4 cases, both EBV and KSHV were present. On the contrary, all 22 classic KS specimens were negative for human herpesvirus-6 sequences. Two of 3 patch and the 1 nodular lesions from AIDS-related KS patients examined were positive for KSHV but negative for both EBV and HHV-6 sequences. Furthermore, we evaluated the prevalence of KSHV sequences in the normal population of the same geographical area. Thirteen peripheral blood mononuclear cell samples, 9 salivary gland tissues and 6 saliva samples from healthy subjects were invariably found negative for KSHV, using the same PCR technique. Of interest, 2 of 11 hyperplastic tonsils harboured these herpesvirus-like sequences, suggesting that, like other herpesviruses, the KS- associated agent may be harboured in a proportion of normal individuals and tonsils may represent at least one of the possible reservoirs of this putative lymphotropic gamma-herpesvirus in vivo.

Acquired Immunodeficiency Syndrome↗

Number and distribution of melanocytic nevi in individuals with a history of childhood leukemia.

BACKGROUND: An increased number of melanocytic nevi at the termination of chemotherapy has been documented in children with hematologic malignancies. The persistence of the increased number of nevi over time and the relationship with personal (e.g. phenotype) and disease related variables remain to be explored. METHODS: One hundred Italian patients diagnosed as having acute lymphatic or myeloid leukemia, after 1975, were recruited and compared with a group of 100 control individuals drawn from friend of the enrolled patients. Information regarding lifetime sun exposure, phenotypic characteristics, and number of nevi was collected by experienced dermatologists. Counts of nevi were expressed both as totals and as counts per unit of body surface area ("density"). Multiple linear regression analysis was employed to control for potentially confounding factors when comparing patients and controls. RESULTS: The patients and controls were fairly comparable in terms of constitutional characteristics, but the patients had a significantly higher number and density of nevi > or = 2 mm or larger in diameter. In addition, patients had a greater number of large nevi ( > or = 6 mm in greatest dimension), and of nevi in unusual areas, such as the palms and soles. Differences in nevus density between patients and controls were notably maintained in the older age group ( > 12 years). None of the disease-related factors analyzed (e.g. treatment protocol and radiotherapy), appeared to be significantly correlated with nevus density. CONCLUSIONS: Patients with a history of childhood leukemia have a sustained increase in their nevus density. A fairly convincing body of evidence indicates that a large number of melanocytic nevi is the strongest risk factor for melanoma. Therefore, the utility of periodic skin examination of these should be considered.

Acute Disease↗

Significance of transient ST-T segment changes during dobutamine testing in Q wave myocardial infarction.

OBJECTIVES: We evaluated dobutamine stress electrocardiography for detecting potentially reversible contractile dysfunction or residual ischemia in the infarct-related area. BACKGROUND: ST-T segment changes in pathologic Q wave leads during stress testing may reflect contractile reserve, inducible ischemia or passive mechanical stretching. Dobutamine echocardiography allows detection of contractile reserve at low doses and inducible ischemia at high doses. METHODS: We used low (5 to 10 microg/kg body weight per min) and high doses (20 to 40 microg/kg per min) of dobutamine in 49 patients with a previous Q wave myocardial infarction and analyzed the relation between ST-T segment changes in pathologic Q wave leads and regional contraction. RESULTS: At low dose dobutamine, regional contraction improved in the infarct-related area in 23 patients. New or further ST segment elevation and pseudonormalization of negative T waves developed at low doses more frequently in patients with than without contractile reserve (both p < 0.001), giving a sensitivity of 43.5% and 60.9% and a specificity of 100% and 96.2%, respectively. At high dose dobutamine (43 patients), new or further ST segment elevation and pseudonormalization of negative T waves, occurring beyond those observed at low doses, had a low predictive accuracy for contractile reserve (sensitivity of 9.5% and 14.3% and specificity of 68.2% and 81.8%, respectively). Pseudonormalization of negative T waves at high dose dobutamine was 100% specific (but only 25% sensitive) for homozonal ischemia. CONCLUSIONS: ST segment elevation or pseudonormalization of negative T waves, or both, is indicative of contractile reserve in the infarct-related area when either develops at low dose dobutamine, but may be associated with worsening or no change in contractile function at high doses.

Aged↗

Primary thrombocythemia and pregnancy: treatment and outcome in fifteen cases.

Pregnancy in patients with primary thrombocythemia (PT) is reported to be often complicated by recurrent abortion and fetal growth retardation. Fifteen pregnancies in nine patients with PT are reported. Nine pregnancies had a good outcome, with the birth of a healthy infant. There were two spontaneous abortions and three intrauterine deaths. One pregnancy was electively terminated after extensive thrombosis in the splanchnic district requiring surgical entero-resection. In five pregnancies the mother received no treatment; in ten pregnancies acetylsalicylic acid (ASA) was prescribed to the mother as soon as she was found pregnant, subcutaneous heparin was added from the middle trimester in seven cases. In patients treated with ASA and subcutaneous heparin pregnancies had a good outcome. Administration of ASA and heparin during pregnancy appears to improve the outcome in patients with PT and can prevent severe maternal complications, but requires close monitoring.

Adult↗

A novel mechanism for the origin of supernumerary marker chromosomes.

A ring chromosome 3 and a 47th chromosome formed by the portions of 3p and 3q distal to the r(3) breakpoints were found in a girl with mental retardation and minor facial anomalies. The supernumerary chromosome 3, rea(3), had a primary constriction inside its 3p portion (3p23) and was consistently stable both in lymphocytes and fibroblasts. In situ hybridization with alphoid probes revealed that the r(3) maintained its wild-type-centromere, whereas the rea(3) showed no alphoid-related signals. This case and a similar one recently reported demonstrate that acentric fragments can acquire a new centromere and become stable, and that supernumerary marker chromosomes can also originate by the junction of the acentric portions distal to the centric region forming a ring. The possibility of such a chromosome segregating will depend on its ability to (re)activate a new centromere.

Adult↗

Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry.

PURPOSE: To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies. PATIENTS AND METHODS: Three hundred sixty consecutive patients (118 males, 242 females, median age 39 years [range 2 to 78]) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant (LAC) (n = 326) and/or raised immunoglobulin G anticardiolipin antibodies (IgG ACA) (n = 185) were collected from 16 Italian institutions and prospectively observed for a median of 3.9 years (range 0.5 to 5). Main endpoints were the occurrence of arterial or venous thrombosis, the outcome of pregnancies, and any severe complications leading to hospitalization or death. RESULTS: Thirty-four patients developed a thrombotic complication, with a total incidence of 2.5% patient-years. Multivariate logistic regression analysis identified two independent risk factors for thrombotic events: a previous thrombosis (RR 4.9; 95% CI, 1.76 to 13.7; P < 0.005) and IgG ACA titer above 40 units (RR 3.66; 95% CI, 1.24 to 10.8; P < 0.01). A total of 28 pregnancies were observed in 25 women and 11 (39%) were abortive. Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion (9/16, 56%) than in asymptomatic women (2/12, 17%) (P = 0.035). Four patients developed non-Hodgkin's lymphoma during the follow-up. Eighteen patients died. Vascular events and hematological malignancies represented the most frequent causes of death (n = 5 for each). CONCLUSIONS: The present study shows that: (a) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis; (b) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome; (c) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies.

Adolescent↗

Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching.

Cross-species comparison is an effective tool used to identify genes and study their function in both normal and pathological conditions. We have applied the power of Drosophila genetics to the vast resource of human cDNAs represented in the expressed sequence tag (EST) database (dbEST) to identify novel human genes of high biological interest. Sixty-six human cDNAs showing significant homology to genes causing Drosophila mutant phenotypes were identified by screening dbEST using the "text string' option, and their map position was determined using both fluorescence in situ hybridization (FISH) and radiation hybrid mapping. Comparison between these genes and their putative partners in Drosophila may provide important insights into their function in mammals. Furthermore, integration of these genes into the transcription map of the human genome contributes to the positional candidate approach for disease gene identification.

Amino Acid Sequence↗

Reliability and accuracy of reporting cervical intraepithelial neoplasia (CIN) in 15 laboratories throughout Italy: phase 1 of a national programme of external quality control in cervical screening. The National Working Group for External Quality Control in Cervical Screening.

This paper reports results of a first phase of a pilot study to assess and improve quality of diagnoses in cervical cytological laboratories located throughout Italy. It represents the first phase of an External Quality Assurance programme (EQA). In the first phase, two sets of cervical smears representing a range of diagnoses were circulated among participating laboratories. Responses were recorded on a standardized form. Participants were asked to assess the adequacy of the smear and formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and judge the degree of diagnostic difficulty of each slide. Crude index of agreement, unweighted and weighted kappas, diagnostic specific kappas, sensitivity and specificity as well as clinical indices of variability were calculated. In the second phase, two additional sets of slides were circulated after discussion of the first phase. There was striking variability between laboratories, both in terms of diagnoses offered and recommendations for management on individual slides. Assessment of the degree of difficulty of each slide was also very variable. Discrimination between CINII and CINIII was poor, confirming the choice of merging these two categories in the Bethesda classification. However, discrimination between CINI and CINII was also unsatisfactory. The results were discussed in workshops and it was possible to reach a consensus diagnosis in 35 of 40 smears. This study confirms the need for external quality control programmes.

Clinical Laboratory Information Systems↗