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Biomedical subjects

M Rinaldi

Publications and source records attributed to M Rinaldi.

At least 37 records · Page 2Linked to original sources

Heart transplantation in patients with amyloidosis: single-center experience.

INTRODUCTION: Amyloidosis is a systemic disease. Heart transplantation in this subset of patients is contraindicated by the majority of authors. In our center, patients with heart failure due to amyloidosis have been evaluated for cardiac transplantation since 1991. The aim of this study was to analyze the outcome of these patients waiting for transplant and the effectiveness of this therapy. MATERIALS AND METHODS: Since 1991, eight patients affected by amyloidosis have been evaluated and enrolled on the waiting list for transplant: five affected by AL lambda type; two by APO A1; and one by TTR. Four were transplanted, three died waiting for a donor (two from cardiac failure, one from sudden death), and one has been recently transplanted after 17 months on waiting list. RESULTS: Since 1985, 713 patients underwent heart transplantation in our center, five of whom were affected by amyloidosis (0.7%). Two are still alive (60 and 41 months) without evidence of cardiac amyloidotic infiltration. One patient recently underwent a combined heart-liver transplantation. Two patients died after the intervention: one sudden death after 23 months with amyloidotic infiltration of transplanted heart, and one multiple organ failure (MOF) due to progression of the systemic disease. CONCLUSIONS: Despite the small size of the group preventing us from drawing definitive conclusion, heart transplantation may prevent therapy to arrest organ damage in patients with isolated cardiac involvement. Cardiac events are the main cause of death. Patients must be followed-up for evolution of systemic disease. The midterm survival is encouraging.

Amyloidosis↗

Influence of biotic and abiotic factors on human pathogens in a finished compost.

The role of indigenous microflora of a finished compost, defined NK12, on the growth suppression of pathogens under different moisture and temperature storages was investigated. Total count of mesophilic and thermophilic bacteria was evaluated by the most probable number method and growth of seeded Salmonella arizonae 3924 serogroup B and enteropathogenic Escherichia coli 84 M in NK12 at different moisture temperature conditions was monitored. Results on sterile and non-sterile NK12 were compared. In all tested experimental conditions, the NK12 indigenous microflora was stable and biologically active. S. arizonae 3924 and E. coli 84 M grew rapidly in sterilized NK12 at different moistures and storage temperatures, and their growth was suppressed in non-sterilized NK12. Pathogens inactivation was lower when compost was stored at 40% and 80% humidity and at 37 degrees C. Our results show that the major role in the pathogens suppression was played by the indigenous microflora of the finished compost, although physical factors too influenced the growth phenomenon.

Colony Count, Microbial↗

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Animals↗

Quality control limits for voriconazole 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 voriconazole disk diffusion tests on Mueller-Hinton agar with 2% glucose and 0.5 micro g of methylene blue per ml. The supplement may be added to the agar before autoclaving, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates with 1- micro g voriconazole disks generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (28 to 37 mm), Candida albicans ATCC 90028 (31 to 42 mm), and Candida krusei ATCC 6258 (16 to 25 mm). Candida tropicalis ATCC 750 was not useful for this purpose.

Agar↗

Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial.

BACKGROUND: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined. OBJECTIVE: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28-31 weeks gestation. DESIGN: Multicentre randomised controlled clinical trial. SETTING: Seventeen Italian neonatal intensive care units. PATIENTS: A total of 230 newborns of 28-31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP. INTERVENTIONS: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome. MAIN OUTCOME MEASURES: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks. RESULTS: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids. CONCLUSIONS: In newborns of 28-31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4.

Continuous Positive Airway Pressure↗

Solitary cardiac metastasis from a clear cell carcinoma of the kidney. A case report and review of the literature.

A case of solitary septal metastasis from a clear cell carcinoma of the kidney is reported in a 55-year-old man who 5 years before had undergone right nephrectomy and adrenalectomy. Since then, he had been successfully treated by means of chemotherapy, radiation therapy, or operated on, at almost yearly intervals, for secondary pancreatic, pulmonary and cerebral single metastases. Diagnosis was obtained by routine computed tomography. The septal mass was surgically removed and the patient was discharged on the 4th postoperative day.

Adenocarcinoma, Clear Cell↗

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↗

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↗

Invasive mycotic infections caused by Chaetomium perlucidum, a new agent of cerebral phaeohyphomycosis.

We report the first two cases of invasive human mycoses caused by the phaeoid ascomycete, Chaetomium perlucidum, and review the English literature regarding invasive Chaetomium infections. Fatal disseminated disease involving the brain, heart, lungs, and spleen is described in an acute myelogenous leukemia patient. A second patient with a history of asthma and chronic bronchiectasis experiencing right-middle-lobe syndrome grew C. perlucidum from lung tissue. This study adds C. perlucidum to the list of other known neurotropic Chaetomium species, C. atrobrunneum and C. strumarium, and also documents this organism's ability to disseminate beyond the central nervous system.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗