PubMed Health⌕ Search

Biomedical subjects

F Morelli

Publications and source records attributed to F Morelli.

At least 19 recordsLinked to original sources

Postchemotherapy residual masses in germ cell tumor patients: our experience.

BACKGROUND: The nature of post-chemotherapy tumor residuals can be determined only by excision and histological examination, but at present no consensus has been reached as to whether all patients with residual masses should undergo adjunctive surgery. PATIENTS AND METHODS: Between August 1991 and September 2004, 120 patients with metastatic germ cell tumors were diagnosed at our hospital and 35 of these patients (30%) underwent adjunctive surgery after cisplatin-based chemotherapy. If serum tumor markers were still raised salvage chemotherapy was administered. RESULTS: At the time of surgical intervention 30 patients (86%) had a partial remission with normal markers. Necrosis, differentiated teratoma and undifferentiated tumor were found in nine (30%), 19 (63%) and two (7%) of all patients. Five patients (14%) underwent postchemotherapy resections after second-line cisplatin-based combination chemotherapy. Four of the 35 patients died as a result of their malignant germ cell tumor. The median observation time after the initial diagnosis was 99 months (range 15-172 months). CONCLUSIONS: Secondary resection of residual masses after first or second-line chemotherapy is still an essential part of the treatment of metastatic testicular cancer. Resection of mature teratoma or viable cancer adds to long-term event-free and overall survival in these patients.

Adolescent↗

Multicomponent collection as of 2005.

Multicomponent apheresis (MCA) begun in Genoa in 1985 in autologous terms. Named "sequestration" it was the preoperative collection of autologous components (RBC-plasma-platelets) using the same apparatus and harness ready for intraoperative blood salvage. In 1986 the technique was applied to donor platelet apheresis with the goal of reducing the costs of platelet collection and concurrently reducing the risks of viral disease transmission to haematological patients who did receive, in the same transfusion event, the necessary blood components obtained from the same donor. The results of this application were maximized by the so called aggressive MCA by which in selected donors, it is possible to collect 2 units of platelets along with 1 or 2 units of PRBCs. These applications were made possible by the development of the concept of dry-platelet collection according to which platelets are collected in only 20-25 mL of plasma and subsequently resuspended in non-plasma solutions such as T-Sol. A last development of MCC is for RBC apheresis, with the collection of 1-2 units of RBC independently of platelet collection. This is going to be the first step of apheresis as the unique modality of collecting blood leaving the bags to history of blood transfusion. Interestingly it took 15 years to MCC to be rediscovered and appreciated worldwide both for its intrinsic cost saving capabilities offered along with an increasing safety for patients. In terms of donor acceptance it is our experience that, since 1989 no donor has refused MCC, consisting at least in the concurrent collection of plasma along with platelets, but also RBC and or a second unit of platelets.

Blood Donors↗

Hypertriglyceridemia: apheretic treatment.

Patients with extremely high triglyceride levels and associated lipemia are at high risk for acute pancreatitis. Two factors can increase triglyceride-rich lipoproteins; one is overproduction and other is a defect in clearance. Either mechanism can cause hypertriglyceridemia and both may exist simultaneously. Causes can be either primary or secondary. Plasmapheresis is efficacious for severe Hypertriglyceridemia in patients who have not responded to previous therapies. We have treated 15 cases of hypertriglyceridemia complicating the course of patients receiving Cyclosporin A after bone marrow transplantation. Five patients were treated with plasmapheresis, the other ten with cascade filtration. The removal rate for triglycerides was 58.0% for patients treated by cascade filtration and 63.5% for patients treated by plasmapheresis. The removal rates for triglycerides were low possibly as a consequence of early saturation of the filter.

Blood Component Removal↗

Hypercholesterolemia and LDL apheresis.

Several trials have assessed the link between low-density lipoprotein cholesterol (LDL) and the development of coronary heart disease (CHD). LDL apheresis provides an effective role in treating patients with familial hypercholesterolemia (FH) and in preventing the progression of coronary artery disease (CAD). Five different techniques of LDL apheresis are in current use: immunoadsorption (IMA), dextran sulphate-cellulose adsorption (DSA), heparin extracorporeal LDL precipitation system (HELP), double filtration plasmapheresis (DFPP) or lipidfiltration and direct adsorption of lipoprotein using hemoperfusion (DALI). All methods are efficient,but their cost restricts LDL apheresis to the treatment of FH. Indications could include other diseases, but controlled trials are still lacking.

Blood Component Removal↗

Lupus vulgaris developing at the site of misdiagnosed scrofuloderma.

Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis primarily occurring in developing countries. The recent increase in the incidence of tuberculosis, especially due to human immunodeficiency virus (HIV) infections, has led to a resurgence of extrapulmonary forms of this disease. We describe a case of lupus vulgaris in a 33-year-old woman who had a 5-year history of a slowly growing plaque on her neck. The lesion was located at the site of surgery repairing the scar resulting from the incision of a subcutaneous abscess during childhood. This lesion was misdiagnosed as bacterial abscess. Histopathologic examination of the plaque revealed non-caseating tuberculoid granulomas consisting of lymphocytes, epithelioid and giant cells. Staining for acid-fast bacilli and culture from biopsied tissue was negative. Polymerase chain reaction (PCR) for detection of Mycobacterium tuberculosis DNA, performed on a skin biopsy specimen, was positive. A diagnosis of lupus vulgaris developing at the site of a previous misdiagnosed scrofuloderma was made. Conventional antitubercular therapy with rifampicin, isoniazid and ethambutol was administered for 6 months, resulting in resolution of the lesion.

Adult↗

Biomechanics of anterior cruciate ligament reconstruction using twisted doubled hamstring tendons.

We studied the biomechanical properties of a twisted doubled semitendinosus and gracilis graft. We applied an un-axial load in order to reproduce the kinematics of a reconstructed anterior cruciate ligament (ACL). A modified cryo-jaw clamp system was used to minimize soft tissue slippage. The lower grip, after fixation of the free ends of the tendons, was rotated 45 degrees, translated 1 cm, and bent 40 degrees, simulating a knee sprain. The graft was tested to failure using a servohydraulic machine. The specimen from one knee of seven unembalmed cadavers was assigned to the untwisted (parallel) bundles group, while its pair was assigned to the twisted group. For the parallel bundles group, the mean maximum load was 1,709.3+/-581.9 N, for the twisted group 2,428.3+/-475.4 N (P<0.05). The mean stiffness was respectively 213.6+/-72.4 N/mm and 310.3+/-97.3 N/mm (P=0.08). Although caution should be used in extrapolating the results to clinical estimates of the strength of hamstring grafts, the results of the present study could justify the use of twisted semitendinosus and gracilis bundles in ACL reconstruction.

Aged↗

Synthesis of novel anti-inflammatory peptides derived from the amino-acid sequence of the bioactive protein SV-IV.

SV-IV is a basic, thermostable, secretory protein of low Mr (9758) that is synthesized by rat seminal vesicle (SV) epithelium under strict androgen transcriptional control. This protein is of obvious pharmacological interest because it has potent nonspecies-specific immunomodulatory, anti-inflammatory, and pro-coagulant activities. In evaluating the clinical relevance and the possible use in medicine of SV-IV, we became interested in the study of its structure-function relationships and aimed to identify in its polypeptide chain specific peptide fragments possessing the marked anti-inflammatory properties of the protein not associated with other biological activities (pro-coagulation and immunomodulation) typical of this molecule. By using two different experimental approaches (the fragmentation of the protein into peptide derivatives by chemical methods and the organic synthesis on solid phase of selected peptide fragments), data were obtained showing that in this protein: (a) the immunomodulatory activity is related to the structural integrity of the whole molecule; (b) the anti-inflammatory activity is located in the N-terminal region of the molecule, the 8-16 peptide fragment being the most active; (c) the identified anti-inflammatory peptide derivatives do not seem to possess pro-coagulant activity, even though this particular function has been located in the 1-70 segment of the molecule.

Amino Acid Sequence↗

Phosphorylation of seminal vesicle protein IV on Ser58 enhances its peroxidase-stimulating activity.

In this study we show that SV-IV, a major immunomodulatory, anti-inflammatory, and sperm immunoprotective protein secreted from the rat seminal vesicle epithelium, acts in vitro as a substrate of protein kinase C (PKC) competing efficiently with H1 histone, a very well known PKC substrate. Electrospray mass spectrometry (ES-MS) analysis demonstrated that approximately 10% of the native SV-IV molecules were phosphorylated by PKC and that such a modification involved only a single serine residue (Ser58) out of the 22 occurring in the protein. Interestingly, this modification produced a substantial enhancement (approximately 50%) of the native SV-IV's ability to stimulate the activity of both horseradish peroxidase (POD) and selenium-dependent glutathione peroxidase (GPX), an enzyme that is known to protect the mammalian spermatozoa from oxidative stress and loss of motility in the female genital tract following ejaculation. In contrast, the phosphorylation of SV-IV on Ser58 did not produce any effect on the anti-inflammatory properties of SV-IV, as measured by its ability to inhibit the phospholipase A2.

Amino Acid Sequence↗

Combination of paclitaxel and etoposide in the treatment of advanced non-small cell lung cancer: a phase I-II study.

Thirty-six patients (pts) with unpretreated advanced non-small cell lung cancer (NSCLC) stages IIIB and IV were enrolled in this two-stage phase I-II study aimed to establish the maximum tolerated dose (MTD) of paclitaxel and to evaluate the efficacy and safety of paclitaxel combined with etoposide every 3 weeks for a maximum of 6 courses, increasing the dose of paclitaxel according to a modified Fibonacci scheme. Nineteen pts were enrolled in the first stage and 17 pts in the second stage. The characteristics of the pts were as follows: median age 56 years (40-70), median Karnofsky's Performance Status 80% (70-80), 11 pts were stage IIIB and 25 pts stage IV. The doses of etoposide administered were 50 mg/m2 for 15 pts and 100 mg/m2 for 21 pts. MTD has not been reached and the study proceeded with the dose of paclitaxel 250 mg/m2. We obtained 9 (25%) partial remissions (PR) and 11 (31%) stable disease (SD) in 33 objectively evaluable pts. Median time to progression (TTP) was 4 months (0.3-21), median survival was 9.3 months (0.3-27). The main toxicity was neutropenia and neurotoxicity, while the gastrointestinal toxicity was mild. Two pts deceased after the first course. The causes of death were necrotizing enteritis in the first pt and congestive heart failure in the second pt. A total of 156 courses were administered at 7 dose levels, with a median of 4 courses per patient (1-6). The results seem to support the use of this combination in advanced non-small cell lung cancer.

Adult↗

Treatment of v-Ki-ras-transformed SVC1 cells with low retinoic acid induces malignancy reversion associated with ras p21 down-regulation.

The effect of nontoxic, low concentrations (10(-8) M) of retinoic acid (RA) for a relatively long time (28 days) on a Kirsten ras-virus transformed cell line (Ki-SVC1), derived from the rat seminal vesicle epithelium, was investigated. In these experimental conditions, the cell treatment with RA induced a decrease of the proliferation rate, apoptosis and a marked reduction of both anchorage-independent growth and tumorigenicity. These biological responses were either preceded or associated with important changes in adenylate cyclase/protein kinase C signaling pathways, the activation of important apoptosis-linked genes and a marked decrease of the v-Ki-ras p21 protein. The significance of these findings is discussed.

Adenylyl Cyclases↗

Inhibition of antithrombin by protein SV-IV normalizes the coagulation of hemophilic blood.

The aim of the study was to evaluate the effect of the protein Seminal Vesicle Protein No. 4 (SV-IV), a potent inhibitor of antithrombin III (antithrombin), on the coagulation of blood obtained from patients affected by hemophilia A. In the coagulating blood of these patients, the antithrombin/thrombin ratio was found to be markedly higher (about 44) than in normal individuals (about 4. 4). This high ratio was related to the low efficiency of thrombin-generating reactions induced by the factor VIII deficiency and to the high levels of free (not bound to serine proteases) antithrombin present in the hemophilic serum (antithrombin concentration was the same in normal and hemophilic plasma). The elevated concentration of free antithrombin in hemophiliacs was primarily a consequence of a reduced consumption caused by the scarce availability in the hemophilic serum of factors Xa and IIa, which are serine proteases possessing strong binding affinity for antithrombin. Addition of SV-IV to coagulating hemophilic blood reduced markedly the serum antithrombin and thrombin-antithrombin complexes, normalizing, as a consequence, the clotting time and other coagulation parameters. Similar results were obtained by using appropriate concentration of factor VIII.

Antithrombin III↗

Sodium butyrate/retinoic acid costimulation induces apoptosis-independent growth arrest and cell differentiation in normal and ras-transformed seminal vesicle epithelial cells unresponsive to retinoic acid.

Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. We studied their effect on normal (SVC1) or v-Ki-ras-transformed (Ki-SVC1) rat seminal vesicle (SV) epithelial cell lines. The treatment of these cells with 10(-((7( M RA did not produce significant changes in the morphological and biochemical parameters analyzed. When RA was used in combination with 2 mM NaB, the treatment induced substantial morphological changes, apoptosis-independent growth arrest, up-regulation of tissue transglutaminase (tTGase), and down-regulation of beta and gamma RA receptor (RAR) mRNA expression. The same cells did not express RAR alpha either before or after NaB/RA treatment. A similar treatment did not change the amount of mRNA coding for the protein SV-IV (a typical differentiation marker of the SV epithelium) in normal or ras-transformed cells nor the level of v-Ki-ras mRNA in Ki-SVC1 cells. These findings suggest that a defective RA/RARs signaling pathway is probably the biochemical condition that underlies the unresponsiveness to RA of our in vitro culture system, and indirectly points to the possibility that the NaB/RA-induced effects were brought about by a cooperation at the transcription level between the histone deacetylase inhibitory activity of NaB and the ability of RA/RAR to modulate the expression of various genes involved in the control of cell growth and differentiation.

Animals↗