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Biomedical subjects

E Rossi

Publications and source records attributed to E Rossi.

At least 127 records · Page 7Linked to original sources

VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.

PURPOSE: The aim of this multicenter randomized study was to compare conventional therapy with conventional plus high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) as front-line treatment for poor-prognosis non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between October 1991 and June 1995, 124 patients, aged 15 to 60 years, with diffuse intermediate- to high-grade NHL (Working Formulation criteria), stages II bulky (> or = 10 cm), III, or IV were enrolled. Sixty-one patients were randomized to receive etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) for 12 weeks and cisplatin, cytarabine, and dexamethasone (DHAP) as a salvage regimen (arm A), and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT (Arm B). RESULTS: There was no significant difference in terms of complete remissions (CRS) in the two groups: 75% in arm A, and 73% in arm B. The median follow-up observation time was 42 months. The 6-year survival probability was 65% in both arms. There was no difference in disease-free survival (DFS) or progression-free survival (PFS) between the two groups. DFS was 60% and 80% (P = .1) and PFS was 48% and 60% (P = .4) for arms A and B, respectively. Procedure feasibility was the major problem. In arm B, 29% of enrolled patients did not undergo HDT and ABMT. A statistical improvement in terms of DFS (P = .008) and a favorable trend in terms of PFS (P = .08) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed. CONCLUSION: In this study, conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results. However, our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients.

Adolescent↗

Five day intermittent vs seven day continuous 2-chlorodeoxyadenosine infusion for the treatment of hairy cell leukemia. A study by Italian Group for the Hairy Cell Leukemia.

The new purine-analogue 2-chlorodeoxyadenosine (2-CdA) has proved to induce an high CR rate and a long lasting disease free survival. In this study we compare the efficacy and toxicity of 2-CdA employed in two different schedules (A and B). Forty-one patients have been enrolled from 1994: 22 p. (group A) were treated with a single cycle of 2-CdA given as two hour i.v. infusion on 5 consecutive days (0.15 mg/kg/die); while 19 p. (group B) with continuous i.v. infusion for 7 consecutive days (0.10 mg/kg/die). Response criteria were those proposed by NCI. The Hairy Cell Index (HCI) was calculated using DBA44 MoAb. At three months, the responses in group A (19/22) were: 5 CR (26.3%), 6 GPR (31.5%), 5 PR and 3 NR.; in group B (17/19): 6 CR (35.3%), 3 GPR (17.6%), 4 PR and 4 NR. Overall response at six months was respectively 84.2% and 76.5%. At six months the responses were: in group A (18/22): 9 CR (50%), 4 GPR (22.2%), 3 PR, 2 NR; in group B (16/19): 4 CR (25%), 6 GPR (37.5%), 3 PR, 3 NR. Overall response at 6 months was respectively 88.8% (group A) and 81.2% (group B). The 5 day intermittent schedule appears efficient, well tolerated and suitable for out-patient treatment. DBA44 MoAb appears useful to better define the HCI and to distinguish CR from GPR.

Adult↗

[Nine consecutive patients with gallstone ileus. Personal experience].

INTRODUCTION: Gallstone ileus is a mechanical obstruction of the gastrointestinal tract caused by the impaction of one or more gallstones within the bowel lumen. The insidious clinical presentation and the lack of specific signs of biliary disease are responsible for the delayed preoperative diagnosis which leads to an overall mortality rate of 15%. MATERIAL AND METHODS: A series of 9 consecutive patients (7 women and 2 men, age ranging from 17 to 83 years), with surgically proved gallstone ileus, was retrospectively reviewed: the authors report the radiologic procedures performed preoperatively and the diagnostic findings. Plain abdominal radiographs were performed in 4 of 9 patients, abdominal US in 4 and CT in 7 patients. All radiologic examinations were retrospectively reviewed by all authors independently, to recognize the different signs of gallstone ileus. RESULTS: The signs of Rigler's triad (small bowel obstruction, ectopic gallstones and air in the biliary tree) were observed on plain abdominal films in two cases, and ectopic gallstones and pneumobilia in two cases. The ectopic gallstones and the small bowel obstruction were demonstrated on abdominal US images in three cases. Rigler's triad was identified on abdominal CT images in 4 cases, while two findings (small bowel obstruction and ectopic gallstones) were observed in three cases. CONCLUSIONS: When the bowel is obstructed by a radiopaque calcified stone, plain radiographs and US of the abdomen are usually enough to diagnose gallstone ileus and no further studies are required.

Adolescent↗

Portal levels of the isoprostane F2 alpha-III, a marker of lipid peroxidation, do not correlate with increased portal pressure in cirrhotic patients.

BACKGROUND: Isoprostane F2 alpha-III (iPF2 alpha-III), a recently described member of a family of prostaglandin F2 alpha isomers and a biologically active end-product of lipid peroxidation, has been reported to increase portal pressure in cirrhotic rats. We found that its urinary levels were elevated in cirrhotic patients. METHODS: To investigate whether portal levels of iPF2 alpha-III were elevated in cirrhotic patients and whether there was a relationship between these levels and the portal pressure in the same patients, peripheral and portal plasma from cirrhotic patients (n = 18) undergoing elective transjugular intrahepatic portosystemic shunt and appropriate controls (n = 18) were assayed for iPF2 alpha-III levels by using a gas chromatography/mass spectrometry assay. Portal pressure was measured in all cirrhotic patients. RESULTS: Cirrhotic patients had higher peripheral plasma levels of iPF2 alpha-III [78 (27-150) pg/mL] than controls [18(10-30)pg/mL] (P < 0.001). Portal iPF2 alpha-III levels were higher than plasma peripheral levels [129(50-375) pg/mL; P < 0.0001]. No correlation was found between peripheral and portal levels of iPF2 alpha-III (Rho = 0.17, P = 0.5). Portal levels of iPF2 alpha-III and portal pressure did not correlate (Rho = 0.17, P = 0.49). CONCLUSIONS: This study shows that peripheral and portal levels of iPF2 alpha-III, marker of in vivo lipid peroxidation, are elevated in liver cirrhosis. There is no correlation between iPF2 alpha-III portal levels and the portal pressure observed in these patients. These findings suggest that this biologically active isoprostane does not directly contribute to the portal hypertension observed in hepatic cirrhosis.

Aged↗

Haemoglobin synthesis in erythropoietin-stimulated J2E cells does not require increased numbers of transferrin receptors.

Changes in transferrin-receptor numbers and iron utilisation were monitored during erythropoietin-induced maturation of J2E erythroid cells. Uptake of transferrin and iron doubled 24 h after exposure to erythropoietin, due to a twofold rise in surface transferrin receptors. In addition, a tenfold increase in iron incorporation into haem was observed after erythropoietin stimulation, as iron taken up from transferrin was directed towards haem biosynthesis and away from storage in ferritin. The rise in iron chelation into haem correlated extremely well with haemoglobin synthesis. However, the increase in numbers of transferrin receptors was not essential for haemoglobin synthesis; rather, it was linked with a burst in proliferation stimulated by erythropoietin. We have shown previously that amiloride blocks erythropoietin-enhanced proliferation of J2E cells, but potentiates maturation [Callus, B. A., Tilbrook, P. A., Busfield, S. J. & Klinken, S. P. (1995) Exp. Cell Res. 219, 39-46]. Here we demonstrate that amiloride suppressed the hormone-induced increase in transferrin receptors, whereas the enhanced incorporation of iron into haem was not inhibited. Similarly, when sodium butyrate was used to induce differentiation of J2E cells, proliferation ceased and surface transferrin receptors remained unaltered, while haemoglobin production was accelerated. It was concluded from these experiments that the erythropoietin-stimulated rise in transferrin receptors during the final stages of J2E cell maturation is linked to cell division, and is not essential for haemoglobin synthesis.

Amiloride↗

Multiple congenital anomalies, brain hypomyelination, and ocular albinism in a female with dup(X) (pter-->q24::q21.32-->qter) and random X inactivation.

We report on an 18-month-old girl with multiple congenital anomalies (prominence of the metopic suture, fine hair, club foot, absence of the 12th rib, brachydactyly) and severe mental retardation. The funduscopic examination showed diffuse retinal hypopigmentation. Brain magnetic resonance image (MRI) showed signs of diffuse hypomyelination. On cytogenetic and molecular evidence, the karyotype was 46,X,dirdup(X) (pter-->q24::q21.32-->qter). The duplication of the PLP gene, involved in Pelizaeus-Merzbacher disease, was confirmed by fluorescent in situ hybridization (FISH). Both cytogenetic and molecular studies on the X chromosome inactivation status indicated a random pattern in lymphocytes and fibroblasts. This patient appears to be the first case of a female bearing a large duplication of Xq with a random X inactivation. The phenotype of this patient is compared to that of previously reported cases with Xq duplication.

Abnormalities, Multiple↗

Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Adult↗

An improved test to identify aPC-resistant factor V-Leiden.

A functional clotting assay was recently reported to detect the factor V-Leiden mutation (R506Q) in patients receiving oral anticoagulants and in patients with Lupus Anticoagulant inhibitor. The original assay (Dahlback) to detect resistance to activated protein C (aPC-resistance) frequently gave unreliable findings in these patients. The change in the method is the use of bovine thromboplastin in a PT-derived assay, with a 1:10 sample dilution. In these conditions a reference normal plasma gives a prolongation of more than 35 seconds, while samples with a heterozygous or homozygous mutation give a prolongation respectively of 10-18 seconds or less 2 seconds. The test is easily automated and quickly performed on ACL/3000, and the reproducibility is good.

Animals↗

Primary repair of isolated ventricular septal defect in infancy guided by echocardiography.

Between 1989 and 1995, 96 consecutive infants affected by isolated ventricular septal defect (VSD) were submitted for primary correction at a median age of 4 months. Of the 96, 60 (group I) underwent surgery on the base of a 2-dimensional Doppler echocardiographic (DD echo) test alone. The preoperative DD echo anatomic definition of the type of VSD was confirmed at surgery in all 60 patients without false-positive results in terms of additional cardiac anomalies. There were 2 false-negatives: in 2 patients an associated cardiac anomaly was not detected by DD echo and required a second surgical procedure after postoperative cardiac catheterization. During the same period 36 infants (group II) underwent surgical closure of isolated VSD on the basis of cardiac catheterization and angiocardiography in addition to DD echo. The retrospective comparison between the 2 groups revealed no significant difference in terms of sensitivity and specificity of the diagnostic tools, early and late mortality after surgical correction, postoperative hospital stay, and need for late cardiac catheterization and surgery. We conclude that after an accurate selection, most of the infants with uncomplicated VSD can safely undergo primary repair on the basis of DD echo alone.

Cardiac Catheterization↗

A novel zinc finger-containing RNA-binding protein conserved from fruitflies to humans.

The Drosophila lark gene encodes an essential RNA-binding protein of the RNA recognition motif (RRM) class that is required during embryonic development. Genetic analysis demonstrates that it also functions as a molecular element of a circadian clock output pathway, mediating the temporal regulation of adult emergence in the fruitfly. We now report the molecular characterization of a human gene with significant similarity to lark. Based on fluorescence in situ hybridization and radiation hybrid mapping, the human gene has been localized to chromosome region 11q13; it is closely linked to several identified genes including the locus of Bardet-Biedl syndrome type 1. The lark-homologous human gene expresses a single 1.8-kb size class of mRNA in most or all tissues including brain. Additional database searches have identified a mouse counterpart that is virtually identical to the human protein. Similar to lark protein, both mammalian proteins contain two copies of the RRM-type consensus RNA-binding motif. Unlike most RRM family members, however, the Drosophila and mammalian proteins also contain a retroviral-type (RT) zinc finger that is situated 43 residues C-terminal to the second RRM element. Within a 184-residue segment spanning the RRM elements and the RT zinc finger, the human and mouse proteins are 61% similar to the Drosophila lark sequence. These common sequence features and comparisons among a large collection of RRM proteins suggest that the human and mouse proteins represent homologues of Drosophila lark.

Adult↗

Role of cysteine residues of rat A2a adenosine receptors in agonist binding.

In the present study, we investigated the role of disulfide bridges and sulfhydryl groups in A2a adenosine receptor binding of the agonist 2-p-(2-carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamidoadenosi ne (CGS 21680). To evaluate the presence of essential disulfide bridges, rat striatal membranes were incubated with [3H]CGS 21680 in the presence of dithiothreitol and binding of the agonist to membranes was measured. The amount of [3H]CGS 21680 which specifically bound, decreased progressively upon pretreatment of membranes with increasing concentrations of dithiothreitol. Pretreatment of rat striatal membranes with 12.5 mM dithiothreitol for 15 min at 25 degrees C resulted in a 2-fold decrease of A2a adenosine receptor affinity for [3H]CGS 21680, and a reduction in the maximal number of binding sites. The presence of agonist or antagonist ligands protected the A2a adenosine receptor sites from the effect of dithiothreitol. We also examined the susceptibility of A2a adenosine receptors to inactivation by the sulfhydryl alkylating reagent, N-ethylmaleimide. When rat striatal membranes were pretreated with N-ethylmaleimide for 30 minutes at 37 degrees C, a decrease in specific [3H]CGS 21680 binding was observed. Pretreatment of membranes with 1 mM N-ethylmaleimide also resulted in a 2-fold reduction of A2a adenosine receptor affinity for [3H]CGS 21680, as well as a slight decrease in the maximal number of binding sites. Neither agonist nor antagonist ligands were effective in protecting the receptor sites from inactivation by N-ethylmaleimide. In contrast, addition of 100 microM guanosine-5'-O-(3-thiotriphosphate) or 5'-guanylylimidodiphosphate were both effective in protecting the receptor sites from inactivation by N-ethylmaleimide. This protective effect was significant but not complete. Our data suggest that disulfide bridges play a role in the structural integrity of the A2a adenosine receptor, furthermore, reduced sulfhydryl groups appear to be important but we do not yet know if they are on the receptor or on the Gs alpha subunit.

Adenosine↗

Lead poisoning in an electrician: a bad substitute for a bad habit.

An electrician presented with a four-month history of unexplained abdominal pain and constipation, which had prompted four hospital admissions and numerous investigations. Blood-film results suggested lead poisoning, and an occupational history revealed that he had chewed about a metre of electrical cable (which contains lead) daily for 10 years as a substitute for smoking.

Abdominal Pain↗