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Biomedical subjects

M Rinaldi

Publications and source records attributed to M Rinaldi.

At least 19 recordsLinked to original sources
PubMed2003

Minimally invasive closure of patent foramen ovale through port-access surgery.

We present here our experience of patent foramen ovale closure through a mini-invasive surgical technique. With the new surgical platform termed Heartport System, it is possible to install extra-corporeal circulation and to obtain cardioplegic arrest of the heart with endovascular techniques. This allows the operation of closure to be entirely performed through a micro-thoracotomy (Port-access surgery) in the right 4th intercostal space. Sixty-one patients underwent this surgical correction and seventeen of them (26%) had a diagnosis of patent foramen ovale, 12 with an history of cerebrovascular accidents. They are all alive and well after a mean follow-up of 16 months, with no recurrence of the inter-atrial communication and free from new neurological events. The post-operative course was uneventful with patients discharged on postoperative day 4. This technique shows a 100% efficacy, minimise surgical trauma, allows a quick recovery and offers excellent cosmetic results with no scarring. We believe that this procedure must be regarded as the "golden standard" for the closure of atrial septal defects

Cardiac Catheterization↗
PubMed2003

Heart transplantation in chemotherapeutic dilated cardiomyopathy.

Anthracycline cardiotoxicity can induce dilated cardiomyopathy (DCM). Nine patients (four men) experienced postchemotherapy DCM: age at time of tumour diagnosis ranged from 1-45 years (mean 13.5 +/- 19 years); interval time between tumour and HT was 3-23 years (mean 10.8 +/- 6.6) and age at HT ranged from 10-65 years (30.8 +/- 20.1). Interval between end of chemotherapy and beginning of cardiac symptoms was 5.71 +/- 4.6 years. Mean age at DCM diagnosis was 19.2 +/- 19.7 (range 1-50 years). Interval between start of chemotherapy and DCM ranged from 1 month to 10 years (mean 3.15 +/- 3.6 years). Tumours were Ewing sarcoma (7-year-old boy), paratesticular rabdomyosarcoma (1-year-old boy), Wilms tumor with pulmonary metastasis (3-year-old girl), bilateral breast carcinoma (45-year-old woman), uterine leiomyosarcoma (44-year-old woman), acute myelocytic leukemia (1.5-year-old boy and 17-year-old girl), and chronic myelocytic leukemia (5-year-old boy). All patients had high pulmonary resistance values. One patient with chronic myelocytic leukemia (14 year-old at HT) died due to graft failure on the first postoperative day. At follow-up (mean, 80.4 +/- 69.3 months) two patients died: a 32-year-old woman (acute myelocytic leukemia) 1 year after HT for sepsis and a 68-year-old woman who had breast adenocarcinoma recurrence 81 months after HT. The remaining patients are alive, in good condition with no difference in survival from other transplanted patients (P =.757). Patients with end-stage postchemotherapy DCM without evidence of tumour recurrence can safely undergo HT.

Adolescent↗
PubMed2003

Quality control limits for fluconazole disk susceptibility tests on Mueller-Hinton agar with glucose and methylene blue.

An international collaborative study was performed in order to propose quality control limits for fluconazole disk diffusion susceptibility tests on Mueller-Hinton agar with 2% glucose and 0.5 micro g of methylene blue per ml. The supplements may be added before autoclaving the agar, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (22 to 33 mm), C. tropicalis ATCC 750 (26 to 37 mm), and C. albicans ATCC 90028 (28 to 39 mm). C. krusei ATCC 6258 was not useful for this purpose.

Agar↗
PubMed2003

Sjögren reticular dystrophy of the retinal pigment epithelium: a case report.

PURPOSE: To describe the clinical manifestations in a patient with Sjögren reticular dystrophy of the retinal pigment epithelium, and the evolution of the disease over a 20-year follow-up period. CASE REPORT: A 45-year-old woman with Sjögren reticular dystrophy of the retinal pigment epithelium was seen for the first time in 1983; the patient underwent 20 years of annual check-ups. RESULTS: Over the follow-up period, fundus photographs, computerized perimetry, electroretinogram, and electro-oculogram findings had either normal or slightly subnormal outcome. CONCLUSIONS: The results confirm that this disease involves only the retinal pigment epithelium and should not be considered a central tapeto-retinal degeneration or late onset retinopathy.

Electrooculography↗
PubMed2003

Lung transplantation in a Jehovah's witness. Case report in a twinning procedure.

Jehovah's Witnesses, patients who refuse blood transfusions, are generally not considered as candidates for lung transplantation owing to the frequent requirement for transfusions. A successful procedure in a Jehovah's Witness is presented and to our knowledge this is the 2(nd) reported case. The patient, a 38-year-old female, type I diabetes, affected by idiopatic pulmonary fibrosis underwent left lung transplantation. From the same pulmonary bloc a twinning procedure was obtained by means of right lung transplantation in a 58-year-old man affected by the same pathology. Surgical strategies employed in achieving a successful outcome, ethical and moral aspects are discussed.

Adult↗
PubMed2002

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm). RESULTS: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05). CONCLUSION: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.

Adult↗
PubMed2002

Experimental murine model of disseminated Pseudallescheria infection.

Pseudallescheria boydii is found in soil and has a worldwide distribution. This fungus was initially identified as a pathogen targeting a variety of tissues. There are fragmentary data in the literature on the in vitro susceptibility of P. boydii to different antifungal compounds. P. boydii is highly refractory to antifungal treatments. In this study, a murine model of disseminated Pseudallescheria infection was developed to evaluate efficacy of different treatment regimens. A clinical strain of P. boydii was studied in normal and neutropenic outbred ICR mice. Several inocula were tested over a range from 1 x 10(3) to 5 x 10(6) cfu. Groups of eight mice were injected with a intravenous dose of one inoculum. Mortality correlated with the dose of the inoculum, and with immunosuppression. Quantitative cultures of various tissues showed initial dissemination of disease in immune competent mice. This was followed by, reduction of tissue burden, except in the brain. In contrast, disseminated infection persisted in most organs in immunosuppressed animals (p < 0.0001). This model should be appropriate for in vivo evaluation of antifungal chemotherapy.

Animals↗
PubMed2001

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Biopsy, Needle↗
PubMed2001

A somatic mutation in the 5'UTR of BRCA1 gene in sporadic breast cancer causes down-modulation of translation efficiency.

Mutations in the 5' UTR which cause increment/decrement of translation efficiency have been recently described as a novel molecular mechanism of disease. Alterations in the consensus sequence for the translation initiation may promote context-dependent leaky scanning of ribosomes and/or initiation from a downstream AUG codon. Initiation of translation from a downstream in-frame AUG codon in BRCA1 gene was recently identified in normal cells and possibly in breast cancer. Here we present further insight into BRCA1 translational pathophysiology investigating the role of the canonical structure of the initiation consensus sequence of BRCA1. We have analysed the effect of a somatic point mutation (117 G>C) in position -3 with respect to the AUG of the BRCA1 gene, identified in a highly aggressive sporadic breast cancer. We constructed chimeric genes encoding the luciferase reporter sequence downstream of the wild type or the mutated BRCA1 5'UTR. These transcripts were tested for their activity in in vitro and in vivo systems. In in vitro transcription/translation assays the estimated translation efficiency of the construct with the mutated BRCA1 5'UTR was 30-50% lower than that with the wild type BRCA1 5'UTR. The same chimeric genes were analysed for their expression in vivo by transient transfection in human cells. While the two constructs were equally transcribed, the plasmid carrying the mutated sequence produced 70% less luciferase activity compared to the wild type sequence. Finally, to obtain a direct evaluation on translational efficiency in vivo, we analysed mRNA translation on translationally active and non-active ribosomes separated from transfected cells. Mutant mRNA was partially localized in subpolysomal particles analytically confirming a polysome recruitment defect. Thus, characterization of BRCA1 5'UTR and translation efficiency seems to provide new insight into BRCA1 role in breast and ovarian cancer pathogenesis.

5' Untranslated Regions↗
PubMed2001

Simultaneous determination of reduced and oxidized glutathione in peripheral blood mononuclear cells by liquid chromatography-electrospray mass spectrometry.

We developed a sensitive and specific liquid chromatography-electrospray mass spectrometric (HPLC-ESI-MS) assay for the simultaneous determination of reduced and oxidized glutathione (GSH and GSSG) in peripheral blood mononuclear cells (PBMC). Following derivatization with N-ethylmaleimide to prevent GSH auto-oxidation, addition of thiosalicylic acid as internal standard, and protein precipitation with cold acetonitrile, the samples were injected into a diol column, eluted with acetonitrile-1% aqueous acetic acid (25:75) and detected by the ESI-MS system. The optimized method exhibited a good detection limit for both analytes (0.01 and 0.05 microM for GSH and GSSG, respectively). Good linearity was reached in the 0.01-20 microM range for GSH and 0.05-20 microM for GSSG. The mean recoveries of GSH and GSSG were 98.5-100.6% and 105.8-111.5%, respectively. The run-to-run repeatability for retention time and peak area was RSD% 0.06 and 1.75 for GSH and 0.18 and 2.50 for GSSG. The optimized method was applied to GSH and GSSG assay in PBMC analyzing 20 healthy individuals.

Chromatography, Liquid↗
PubMed2001

Antibodies elicited by naked DNA vaccination against the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain idiotypic determinants of B-lymphoproliferative disorders specifically react with patients' tumor cells.

Several reports have suggested that the mechanism of protection induced by antiidiotypic vaccination against low-grade lymphoproliferative disorders is likely to be antibody mediated. Here we test the hypothesis that DNA vaccination with the short peptide encompassing the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain (VH-CDR3) may elicit a specific antibody immune response able to recognize the native antigens in the form required for therapy. As a test system, we used the VH-CDR3 sequences derived from two patients with non-Hodgkin's B lymphomas (PA, AS) and one patient with hairy cell leukemia (BA) to immunize outbred Swiss mice. This experimental model could mimic a clinical setting in which different patients present distinct HLA haplotypes. Individual tumor-specific VH-CDR3 sequences were amplified by a two-step procedure and directly cloned into multigenic plasmid vectors (pRC100 and derived) with and without mouse interleukin 2 (mIL-2). Each tumor-specific sequence was characterized by sequencing. Female Swiss mice were vaccinated i.m. with plasmids expressing the tumor-specific VH-CDR3 sequence alone (pRC101-PA), mIL-2 plus the VH-CDR3 sequence (pRC111-PA), or a different unrelated antigen (NS3 of hepatitis C virus; pRC112), the sole mIL-2 (pRC110), and the empty plasmid (pRC100). Boost injections were performed at 3 and 16 weeks from the first vaccination, and sera were drawn before each vaccination and at 6, 9, and 19 weeks. Induction of anti-VH-CDR3s antibodies in the sera and their ability to recognize native antigens on patients' tumor cells were evaluated by FACS analysis. Up to 56% (n = 25) of mice vaccinated with pRC111-PA plasmid and 20% (n = 15) of mice vaccinated with pRC101-PA developed a specific immune response that was maintained throughout 19 weeks of observation in 40% of pRC111-PA-vaccinated mice. No response was detected in sera obtained from mice vaccinated with the other plasmids (n = 45). pRC111-PA injection s.c. was less effective (13%, n = 15) than i.m. injection (53%, n = 15). Indeed, we demonstrated that antibodies elicited by naked DNA vaccination against three different patient-derived VH-CDR3 peptides (pRC111-PA or BA or AS) readily reacted with binding epitopes on the idiotypic proteins expressed on the surface of tumor cells derived from each patient; 60, 40, and 40% of, respectively, PA-, BA-, and AS-vaccinated mice developed specific antibodies. No cross-reactivity was detected among the three different CDR3s against tumor cells derived from the other two patients. The outbred mouse strategy confirmed the significant matching potential of three different VH-CDR3 peptides to be efficaciously presented through different MHCs. We conclude that individual VH-CDR3 DNA vaccination can result in a potentially effective specific immune response against non-Hodgkin's B lymphoma cells by a rapid and low-cost therapeutic approach.

Amino Acid Sequence↗
PubMed2001

Contribution of posture to the maintenance of anal continence.

The anorectal angle (ARA) is believed to provide one of the most important contributions to anal continence. The normal resting angle is approx. 90 degrees, but the erect position may modify the ARA and other parameters usually considered in a proctometrogram. We compared the proctometrogram in different postures to elucidate the role of changes in the ARA in maintaining fecal continence. Sixty-three patients with constipation underwent static proctography. Variations in the ARA, perineal descent, puborectalis muscle length, and pubococcygeal distance were determined during resting, squeezing, and pushing with the patient in the Sims' position (SP); further evaluations used radiographs in resting position but with straight legs, in erect and sitting positions. The resting mean ARA was 95.3 +/- 15 degrees in SP and 79.8 +/- 14 degrees standing erect; the latter value was also significantly less during squeezing (84 +/- 11 degrees). The mean ARA during pushing was 118 +/- 16 degrees. A systematic and statistically significant difference in the mean resting ARA was demonstrated using the baseline of the rectal shape instead of the major rectal axis when measuring the anorectal angle. When sitting on a toilet, the mean resting ARA was significantly wider than in SP. The length of the puborectalis sling at rest did not change but was significantly reduced during squeezing and increased during pushing. The descent of the perineum at rest was near to 0 (-0.089 +/- 1.76 cm) in SP and significantly less when standing (-0.65 +/- 1.9 cm) and during squeezing (-0.97 +/- 1.7 cm). Perineal descent during pushing was +2.94 +/- 2.2 cm. The mean pubococcygeal distance did not change significantly in SP and in the erect position. The erect position thus contributes significantly to the maintenance of fecal continence by sharpening the ARA. This effect is stronger than any active contraction of the puborectalis muscle and is not related to shortening of the puborectalis sling but is secondary to lifting of the pelvic floor.

Adult↗
PubMed2001

Chilaiditi's syndrome. Successful surgical correction by colopexy.

We describe the case of a patient affected by the Chilaiditi's syndrome, the interposition of the small or large bowel between the inferior face of the diaphragm and the liver, a rare anomaly, often asymptomatic. A 50-year-old man came to our outpatients clinic because of persistent pain in the right abdominal region. Two attempts to perform colonoscopy failed because of the impossibility of passing through the transverse colon. A double contrast enema indicated only sigmoid diverticulitis. Only after abdominal radiography was the abnormal position of the right colon noted. At surgery the right colon was totally intraperitoneal and positioned between the diaphragm and liver, which was smaller than normal. The right colon was repositioned and fixed to the anterior abdominal wall. The postoperative course was uneventful and the right abdominal pain disappeared completely. In conclusion, surgical treatment of Chilaiditi's syndrome may be required in cases of persistent abdominal pain.

Colon↗
PubMed2001

Induction chemotherapy with gemcitabine and cisplatin in stage III non-small cell lung cancer.

The necessity of improving the long-term survival of patients with locally advanced non-small cell lung cancer (NSCLC) points out on the one hand the limit of surgery alone and, on the other hand, the need of combined modality therapy, in which the role of chemotherapy to control distant metastases is prominent. Recent experiences support the efficacy of neoadjuvant chemotherapy with or without radiotherapy. Phase II studies show response rates of 50-80% and median survival longer than 2 years. Phase III studies suggest that neoadjuvant chemotherapy improves survival and objective responses, and induces higher percentages of complete resections compared with surgery alone or chemotherapy and radiotherapy. The gemcitabine-cisplatin regimen has proved its efficacy in NSCLC advanced disease with response rate greater than 40% in phase II and III trials. Representing one of the regimens most used in Europe, its activity has been investigated also in the neoadjuvant setting. Phase II studies have reported an average response rate greater than 60%, complete surgical resections in 60-70% of the cases, and 1-year survival of about 60%. A modern tendency is to use neoadjuvant chemotherapy in very early stages of NSCLC. Gemcitabine-cisplatin regimen has been used as a randomised clinical trial (chemotherapy for early stages trial, CHEST) to compare the efficacy of surgery alone versus surgery plus preoperative chemotherapy in early-stage disease (T2-3N0, T1-2N1, T3N1), and to evaluate the progression free survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Neoplastic disease after heart transplantation: single center experience.

OBJECTIVES: Mandatory use of prolonged immunosuppression in organ transplantation is complicated by an increased incidence of cancer. The current study represents a retrospective analysis of the incidence of neoplasms in our heart transplantation program. METHODS: Four-hundred and seventy-four patients (403 male and 71 female; mean age, 48.6+/-12.1 years), with at least 30 days of follow-up, were enrolled in this study. Patients received triple immunosuppression with cyclosporin A, azathioprine and steroids. Moreover, as a prophylactic anti-lymphocyte therapy, 388 patients (82%) were administered RATG, 67 patients (14%) received ALG and 19 patients (4%) OKT3. The mean follow-up time was 71.1+/-43.0 months. RESULTS: Fifty-five patients (11.6%) developed malignant neoplasms. The cancer frequencies were: solid tumors, 55%; non-Hodgkin lymphomas (NHL), 20%; Kaposi's sarcomas, 11%; skin cancers, 9%; undifferentiated sarcomas and myelomas, 5%. Solid tumors mainly affected the lung (39%), bowel (16%), stomach (6.5%), liver (6.5%), pancreas (6.5%) and oral cavity (6.5%). The times to the onset of cancer from transplantation were: Kaposi's sarcoma, 12.7+/-16.8 months; skin cancers, 34.5+/-23.8 months; solid tumors, 54.3+/-38.7 months; NHL, 60.1+/-36.4 months; undifferentiated sarcomas and myelomas, 90.0+/-15.6 months. As determined by univariate and multivariate analyses, sex, number of treated rejections, previous history of tumor, average dose of cyclosporine and prednisone and cyclosporine blood levels did not increase the incidence of malignancies. Univariate analysis suggests a significant correlation between the type of prophylactic immunoglobulins and the average dose of azathioprine with the incidence of neoplasms. Both univariate and multivariate analyses demonstrated a significant correlation between patient's age at the time of transplantation and risk of cancer occurrence (risk increased by 1.074/year; P=0.0056 with multivariate Cox regression). CONCLUSIONS: Cancer is a strong limitation for long-term survival after heart transplantation. The only risk factor recognized is the patient's age at the time of transplant. Furthermore, the type of prophylactic globulins used for induction therapy and some specific immunosuppressant agent (azathioprine) may play a significant role in the development of malignancies after transplantation.

Adult↗