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Biomedical subjects

F Longo

Publications and source records attributed to F Longo.

At least 19 recordsLinked to original sources

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

Humans↗

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Journal Article↗

Pathophysiology and therapeutic possibilities of calcitonin gene-related peptide in hypertension.

Calcitonin gene related peptide (CGRP), a 37 amino acid neuropeptide, is the most potent vasodilator known. Participation of CGRP in hypertension and related diseases, such as preeclampsia or vasospasm after subarachnoid haemorrage, is one of the most studied topics. In this review we summarize the published roles of CGRP in pathophysiology of hypertension in humans and in experimental models. We also discuss the effects of direct administration of CGRP in the treatment of hypertension and of anti-hypertensive drugs that enhance the release or response of endogenous calcitonin gene-related peptide: angiotensin converting enzyme inhibitors, selective antagonists for the angiotensin II receptor, beta-blockers, magnesium sulphate for preeclampsia and rutaecarpine, as well as the possibilities using CGRP in gene therapy for prevention of vasospasm after subarachnoid haemorrage.

Animals↗

Elastic neutron scattering study of water dynamics in ion-exchanged type-A zeolites.

With the aim to investigate, by means of elastic neutron scattering, the effects produced by the cation substitution on the dynamics of water in zeolites, we measured, using a neutron backscattering spectrometer, the temperature dependence of mean-square atomic displacements [u2] derived from window integrated quasielastic spectra of fully and partially hydrated Na-A and Mg50-A zeolites. The results, collected in the 20-273 K temperature range, reveal that, at low temperature, the [u2] shows a harmonic trend independent of hydration and cation substitution, and, at higher temperatures, the onset of a non-Gaussian dynamics of the elastic intensity. This latter takes place at T approximately 200 K and approximately 150 K for fully and partially hydrated samples, respectively. This behavior has been interpreted in terms of reorientational jumps of H atoms described by two-site processes within an asymmetric double-minimum potential. In spite of its simplicity, the model seems to reproduce the rearrangement of the hydrogen bond network of zeolitic water. The fit results indicate a reduced proton mobility by diminishing the water content and by the induced Na+-->Mg2+ ion exchange, in agreement with previous incoherent quasielastic neutron scattering results at higher temperatures.

Journal Article↗

Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to bacillus Calmette-Guérin therapy.

INTRODUCTION: Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS). MATERIAL AND METHODS: Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months. RESULTS: Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2-4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed. CONCLUSION: Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.

Adjuvants, Immunologic↗

Deferiprone: New insight.

Recent results from independent studies suggest that deferiprone is more cardioprotective than deferoxamine. Patients on long-term treatment with deferiprone have a better myocardial magnetic resonance imaging pattern and less chance to develop a new cardiac disease or worsen an existing one. Most of these observations are retrospective and require confirmation from randomized controlled trials. Other new observations regard the effects of combining the two chelators. Most results indicate an additional effect on iron excretion and a significant reduction of the time required to mitigate severe iron overload and to reverse clinical heart disease. Again, these data require confirmation, as they were mostly obtained on individual cases or small groups of patients treated with a wide range of combinations of the two chelators, but the univocity of results is impressive. After many years of controversy, deferiprone is emerging as a useful oral iron chelator that enhances the chances for the patient to have optimal treatment. Well-designed and -conducted studies will help in answering the questions still open.

Agranulocytosis↗

Validation and comparison of analytical methods for the determination of histamine in tuna fish samples.

Histamine is a degradation product of the bacterial decarboxylation of the amino acid histidine, which is present in large amounts in fish tissues of the Clupeidae and Scombridae families and its presence is an indicator of good manufacturing practices and of the state of preservation of some food. A capillary electrophoresis and high-performance liquid chromatography method with diode arrays detection (HPLC-DAD) were compared and validated: no laborious pre-treatment, no clean up and no derivatization was necessary. In both techniques the correlation coefficient exceeded 0.999 for all the analyses carried out during validation. The limit of detection and the limit of quantitation are 1 and 2 mg/kg, respectively, for high-performance liquid chromatography and 0.5 and 1 mg/kg, respectively, for capillary electrophoresis. Good recoveries were observed for the histamine under investigation at all spiking levels and average recoveries were higher than 92% with the relative standard deviation less than 4% for high-performance liquid chromatography and average recoveries were higher than 85% with the relative standard deviation less than 3% for capillary electrophoresis.

Animals↗

Determination of biogenic amines in fish tissues by ion-exchange chromatography with conductivity detection.

Some biogenic amines, such as putrescine, cadaverine, spermidine and histamine, have been found to be useful as quality indices for the decomposition of fish, so research on the simultaneous analysis of various biogenic amines in food is of interest and importance. The intake of histamine may cause an allergic intoxication known as "scombroid poisoning" while secondary biogenic amines can potentiate the toxicity of histamine and in addition can react with nitrite to form carcinogenic nitrosamines. A new method for the simultaneous determination of underivatized biogenic amines based on ion-exchange chromatography with conductivity detector has been developed. The proposed method offers a number of advantages over previous pulsed amperometric detection and integrated pulsed amperometric detection methods such as simpler extraction procedure and sharp peaks. Separations were performed on a new low hydrophobic weak cation-exchange analytical column. This technique is simple, rapid and useful for routine checks in repetitive analyses.

Animals↗

Primary non-Hodgkin's lymphoma of the mandible. Report of a case.

A case of a 45-year-old white man admitted for an osteomyelitis and subsequently diagnosed affected by an IE stage, diffuse high grade large B cell non-Hodgkin's lymphoma of the mandible is reported. The patient presented a swelling in the right mandibular region with paraesthesia of the ipsilateral lower lip without nodal involvement of the neck. After an incisional biopsy, which showed a diffuse high grade large B-cell non-Hodgkin's lymphoma, the patient was staged and treated with CEOP protocol for six courses and subsequently external beam radiation therapy with complete remission of the lesion.

Antineoplastic Combined Chemotherapy Protocols↗

Validation of a high-performance liquid chromatography method for the determination of oxytetracycline, tetracycline, chlortetracycline and doxycycline in bovine milk and muscle.

High-performance liquid chromatography with diode-array detection (HPLC-DAD) was optimised and validated for the determination of tetracyclines in bovine milk and tissues. Milk and tissue samples were extracted and purified using a solid-phase extraction HLB Oasis cartridge and analysed using HPLC-DAD set at 365 nm. The analyses were carried out using the mobile phase of 0.01 M oxalic acid-acetonitrile-methanol (60:25:15, v/v/v) on a C8 column (250 x 4.6 mm I.D., 5 microm). Recoveries of tetracyclines from spiked samples at the three concentrations (0.5, 1 and 1.5) of the maximum residues limits (corresponding to 100 microg/kg for milk and the muscle) were higher than 81.1% in milk and 83.2% in muscle. The method was successfully validated for bovine milk and muscle in compliance with requirements set by draft SANCO/ 1805/ 2000 European Decision. The decision limit (CCalpha) was in the range 113.2-127.2 microg/kg and 107.7-129.9 micro/kg for all compounds in milk and muscle, respectively. The detection capability (CCbeta) was in the range 117.2-131.3 microg/kg and 114.9-133.1 microg/kg for all compounds in milk and muscle, respectively.

Animals↗

Determination of enrofloxacin and its metabolite ciprofloxacin in goat milk by high-performance liquid chromatography with diode-array detection. Optimization and validation.

A high-performance liquid chromatography-diode array detection method (HPLC-DAD) combined with liquid chromatography-mass spectrometry was developed for the determination of enrofloxacin and its metabolite ciprofloxacin in goat milk. The HPLC-DAD method validation was compliant with the "DG SANCO 1805/2000" European regulation. The residues were extracted from milk with phosphate buffer, purified on a C18 Speedisk cartridge SPE (Baker) and then analysed using HPLC-DAD set at 277 nm. The decision limit (CCa) calculated by spiking samples at 100 microg/kg with both analytes, taking into account the maximum residue limit (MRL) of 100 microg/kg established by the European Union for the sum of enrofloxacin and its metabolite ciprofloxacin in milk, was 105.3 microg/kg for enrofloxacin and 105.5 microg/kg for ciprofloxacin. The detection capability (CCbeta) was 110.7 and 110.9 microg/kg for enrofloxacin and ciprofloxacin, respectively. The mean recoveries of the method, calculated by spiking samples at 50, 100 and 150 microg/kg were 84% for enrofloxacin and 88% for ciprofloxacin. The limit of quantification was 20 microg/kg for both analytes. The HPLC-DAD validated method was successfully applied for the first time in goats milk, and proved to be suitable for the sensitive and accurate quantification and confirmation analysis of enrofloxacin and ciprofloxacin for regulatory purposes.

Animals↗

Diagnosis of juvenile hemochromatosis in an 11-year-old child combining genetic analysis and non-invasive liver iron quantitation.

UNLABELLED: Juvenile or type2 hemochromatosis is a rare autosomal recessive disorder which leads to severe iron overload early in life. As in the classic adult form of the disease iron toxicity causes liver cirrhosis, cardiomyopathy, and endocrine complications, but the onset of the disease is anticipated in the second to third decades of life. Experience of this disease in children is limited. Molecular diagnosis is unfeasible because the type2 hemochromatosis gene is still unknown, although it is known that the disease locus maps to chromosome 1q. Combining linkage analysis with markers encompassing chromosome 1 locus and a non-invasive method for liver iron quantitation we diagnosed juvenile hemochromatosis in a presymptomatic stage in an 11-year-old Italian child. A regular phlebotomy protocol reduced iron overload preventing all the disease complications. CONCLUSION: Juvenile hemochromatosis patients have severe iron overload within the first years of life, strengthening the greater iron absorption that occurs in this as compared to other types of hemochromatosis. Early detection is essential, because treatment in presymptomatic stages prevents organ damage.

Child↗

Fatigue is associated with high circulating leptin levels in chronic hepatitis C.

BACKGROUND AND AIMS: Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyse fatigue in CHC and to determine its relationship with disease activity, resting energy expenditure (REE), circulating leptin, and tumour necrosis factor alpha (TNF-alpha). METHODS: Seventy eight CHC patients, 22 healthy controls, and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-alpha. All subjects completed the fatigue impact scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients. RESULTS: Thirty eight of 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of patients was significantly higher than that of controls (53.2 (40.1) v 17.7 (16.9); p<0.0001) and was more pronounced in females (p=0.003). Leptin was increased significantly in CHC patients compared with controls (15.4 (20.7) v 6.4 (4.1) ng/ml; p<0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (r=0.30, p=0.01). This correlation increased when the physical domain of fatigue was included (r=0.39, p=0.0009). Furthermore, a similar positive correlation was found in PBC patients (r=0.56, p=0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load, or the METAVIR score in CHC patients. CONCLUSIONS: Fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.

Adult↗

[Peritoneal papillary serous carcinoma: clinical report].

Peritoneal papillary serous carcinoma (PPSC) is a rare tumour that involves the surface of the peritoneum, with prevalence in female patients and can originate from a single or multicentric focus is here described. A primary peritoneal serous carcinoma is here described. The patient has been treated with paclitaxel 175 mg/m2 and carboplatinum AUC 6.

Aged↗

Psychological impact of news of genetic risk for Huntington disease.

A one-year longitudinal study was conducted investigating the psychological effects of the news of genetic testing for the Huntington disease (HD) gene. Participants were assessed at baseline (before obtaining news of test results) and at three, six, and 12 months after test results on stress-specific symptom measures. Among carriers of the HD gene, a considerable number (55%) showed evidence of neurological impairment at baseline, indicative of HD. Also noteworthy, these individuals had significantly higher psychological symptom scores at baseline than carriers without neurological impairment or noncarriers. Despite this, these individuals were no more aware of their carrier status at baseline than carriers without HD symptoms or noncarriers. Furthermore, the psychological symptom levels of HD carriers with neurological impairment remained elevated across the follow-up assessments. Results for noncarriers and carriers without HD neurological symptoms were consistent with the findings of previous studies indicating that news of genetic testing for the HD gene had limited detrimental impact. The clinical implications of the results are discussed.

Adaptation, Psychological↗