Can a validated website help improve university students' e-health literacy?

Background: The fight against fake news, mainly spread through Internet, is a major public health issue, even among undergraduate students. This study aims to evaluate the effectiveness of a website promoted by the Italian Federation of the Provincial Orders of the Medical Doctors as a first aid communication kit for health topics. Study design: Pre-post study using a web-based survey, conducted in April-May 2019 on Medical students and October-November 2020 on Communication Sciences students at the University of Florence (Italy). Methods. Undergraduate students of both schools were exposed to the use of the "dottoremaeveroche" website. Primary and secondary outcomes measures: the Italian-electronic Health Literacy Scale self-assessment tool was used to examine subjects' electronic Health literacy, and source quality. All responses were rated on a 5-point Likert scale. Changing in perception of abilities were examined using the Wilcoxon test. Results: The 362 participants felt moderately confident in electronic Health Literacy, with an initial Italian-electronic Health Literacy Scale overall mean score of 3.6±0.7 for medical and 3.2±0.8 for communication students. Medical students had a good idea of how to find helpful sources (3.9±0.8) and communication students felt confident in recognizing their quality (3.5±1.0). In contrast, their confidence in using Web information to make health decisions was low (medical: 2.9±1.1; communication: 2.8±1.1). All items improved significantly after "dottoremaeveroche" use (p<.001), with the overall mean score of Italian-electronic Health Literacy Scale increasing to 4.3±0.6 for medical and 4.1±0.8 for communication students. Conclusions: Low electronic health literacy levels can affect public health efforts, as seen during the COVID-19 pandemic. The effectiveness of "dottoremaeveroche" among students showed the usefulness of online educational interventions that, if further implemented, could help combat the spread of infodemic.

Redefining anterior ankle arthroscopic anatomy: medial and lateral ankle collateral ligaments are visible through dorsiflexion and non-distraction anterior ankle arthroscopy.

PURPOSE: A thorough understanding of the arthroscopic anatomy is important to recognise pathological conditions. Although some ankle ligaments have been described as intra-articular structures, no studies have assessed the full visibility of these structures. The purpose of this study was to assess arthroscopic visibility of medial and lateral ankle collateral ligaments. METHODS: Arthroscopy was performed in 20 fresh frozen ankles. The arthroscope was introduced through the anteromedial portal and the anterior compartment was explored in ankle dorsiflexion without distraction. Intra-articular structures were tagged using a suture-passer introduced percutaneously and they were listed in a table according to the surgeon's identification. After the arthroscopic procedure, the ankles were dissected to identify the suture-tagged structures. RESULTS: According to the suture-tagged structures, 100% correlation was found between arthroscopy and dissection. In the anterior compartment, the superior fascicle of the anterior talofibular ligament, the distal fascicle of the anterior tibiofibular ligament and the anterior tibiotalar ligament on the medial side were observed. The deep fascicle of the posterior tibiofibular ligament and the intermalleolar ligament were tagged at the posterior compartment. CONCLUSION: Ankle dorsiflexion and non-distraction arthroscopic technique allows full visualisation of the medial and lateral ankle collateral ligaments: the superior fascicle of the anterior talofibular ligament, the distal fascicle of the anterior tibiofibular ligament and the anterior tibiotalar ligament. When using distraction, posterior structures as the deep fascicle of the posterior tibiofibular ligament and the intermalleolar ligament can be observed with anterior arthroscopy.

Anatomic lectures on structures at risk prior to cadaveric courses reduce injury to the superficial peroneal nerve, the commonest complication in ankle arthroscopy.

PURPOSE: To assess the effectiveness of cadaveric ankle arthroscopy courses in reducing iatrogenic injuries. METHODS: A total of 60 novice surgeons enrolled in a basic cadaveric ankle arthroscopy course were divided into two groups. Group A (n = 32) was lectured on portal placement and use of the arthroscope, whereas group B (n = 28) was in addition lectured on specific portal-related complications. Following the performance of anterior ankle arthroscopy and hindfoot endoscopy, the specimens were dissected and carefully assessed for detection of any iatrogenic injuries. RESULTS: The rate of injury to the superficial peroneal nerve (SPN) was reduced from 25 to 3.6%, in group A compared with B (p = 0.033). Injuries to the peroneus tertius or extensor digitorum longus, the flexor hallucis longus and the tibial nerve or the Achilles tendon were also reduced in group B. Overall, the number of uninjured specimens was 50% (n = 30) and higher in group B (57%) than group A (44%). Lesions to the plantaris tendon, the sural nerve or the posterior tibial artery were more common in group B, however, without reaching statistical significance. Overall, 25 (13.9%) anatomic structures were injured in anterior arthroscopy compared to 18 (5%) in hindfoot endoscopy, out of a potential total of 180 and 360, respectively (p = 0.001). CONCLUSION: Dedicated lectures on portal-related complications have proven useful in reducing the risk of injury to the SPN, the commonest iatrogenic injury encountered in ankle arthroscopy. Hindfoot endoscopy is significantly safer than anterior ankle arthroscopy in terms of injury to anatomical structures.

A step-by-step arthroscopic examination of the anterior ankle compartment.

PURPOSE: Despite the increased use of ankle dorsiflexion without distraction, no reports have specifically addressed the arthroscopic anatomy of the ankle in this position. The purpose of this study was to describe the normal arthroscopic anatomy of the ankle joint, when using the ankle dorsiflexion and the dynamic distraction technique, and to propose an arthroscopic examination system for the anterior ankle compartment. METHODS: Ankle arthroscopy was performed in 20 fresh frozen specimens. Arthroscopic examination was performed with the arthroscope introduced through the anteromedial portal. The anterior compartment was examined in ankle dorsiflexion without distraction. The compartment was examined in four steps: (1) lateral area including the lateral gutter; (2) the central area of the anterior tibial rim; (3) the medial area including the medial gutter; (4) the talar neck. Next, distraction was applied to visualise the anterior compartment again and to examine the central and posterior ankle compartments. RESULTS: Anatomic intra-articular structures were visualised in all specimens. Four intra-articular fat pads, one anteromedial, two syndesmotic and another posteromedial, were constantly observed. A description of the normal arthroscopic anatomy of the ankle using the ankle dorsiflexion and the dynamic distraction technique is detailed for the anterior, central and posterior compartments. CONCLUSION: The ankle arthroscopic procedure without distraction allows constant visualisation of the ATFL's superior fascicle on the floor of the lateral gutter, the ATiFL's distal fascicle laterally and the most anterior margin of the deltoid ligament in the medial gutter (anterior tibiotalar ligament). However, ankle distraction is required to observe the central and posterior compartments, but it does not provide optimal visualisation of the anterior ankle compartment structures. LEVEL OF EVIDENCE: V.

Impact assessment of an educational course on vaccinations in a population of medical students.

BACKGROUND: The inadequate knowledge about vaccinations of healthcare workers, including medical doctors, has certainly contributed to the spread of the vaccine hesitancy. Therefore, it is essential to improve the level of knowledge of future doctors. The aim of the study is to evaluate the impact of a course about vaccinations on the knowledge of medical students. METHODS: Medical students were asked to complete an anonymous questionnaire before and after a seminar on vaccination that they willingly attended. The two questionnaires contained the same 10 questions about vaccines. Only the students who had attended the lecture were allowed to fulfil the post-lecture questionnaires through the learning management system (LMS) called "Moodle". A descriptive statistical analysis of the data collected through the comparative evaluation of the answers before and after the seminar was performed. Mann-Whitney test for two independent samples was used to compare medians score before and after the interventions. RESULTS: A total of 100 medical students filled the pre-lecture questionnaire and 81 of them completed the post-lecture questionnaire. Knowledge of the students on the indication of the MMR (Measles-Mumps-Rubella) vaccine strongly improved after the seminar. Moreover, the number of students who would recommend vaccination for pertussis and influenza during pregnancy increased significantly by 37% and 19% respectively after the seminar and those aware of the need for Herpes Zoster vaccination over the age of 65 increased by 22%. DISCUSSION: For future doctors, a thorough knowledge about vaccinations is increasingly required in order to deal with vaccine hesitancy. Extracurricular seminars about vaccines, provided in the second half of the course of study, can have a highly positive impact.

Anatomy, pathophysiology and classification of posterior tibial tendon dysfunction.

OBJECTIVE: Adult acquired flatfoot deformity is generally associated with a collapsing medial longitudinal arch and a progressive loss of strength of the posterior tibial tendon (PTT). This condition is commonly associated with PTT dysfunction or rupture, which can have an arthritic or a traumatic etiology. Several causes have been proposed to explain the clinical evidence of tendon degeneration observed at the time of surgery including trauma, anatomical, mechanical, inflammatory and ischemic factors. MATERIALS AND METHODS: In this review, we analyzed anatomy, pathophysiology and existing classifications of posterior tibial tendon dysfunction. RESULTS: Anatomical features, and in particular vascularization, expose PTT to major degenerative disorders until rupture. A literature overview showed that a low blood supply of the gliding part of the tendon is linked to a dysfunction and/or a rupture of the PTT in the region located behind the medial malleolus. CONCLUSIONS: PTT low blood supply causes a dysfunction resulting in an abnormal loading of the foot's medial structures. This may be the reason why PTT dysfunction leads to an acquired flatfoot deformity. Conversely, flatfoot deformity may be a predisposing factor for the onset of PTT dysfunction.

Amniotic fluid stem cells: an ideal resource for therapeutic application in bone tissue engineering.

OBJECTIVE: Skeletal diseases, both degenerative and secondary to trauma, infections or tumors, represent an ideal target for regenerative medicine and in the last years, stem cells have been considered as good candidates for in vitro and in vivo bone regeneration. To date, several stem cell sources, such as adult mesenchymal stem cells, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have shown significant osteogenic potential. MATERIALS AND METHODS: In this narrative review, we analyze the possible advantages of the use of AFSCs in the treatment of skeletal diseases, especially through the application of tissue engineering and biomaterials. RESULTS: Among the different sources of stem cells, great attention has been recently devoted to amniotic fluid-derived stem cells (AFSC) characterized by high renewal capacity and ability to differentiate along several different lineages. CONCLUSIONS: Due to these features, AFSCs represent an interesting model for regenerative medicine, also considering their low immunogenicity and the absence of tumor formation after transplantation in nude mice.

Cardiovascular effects of peptide kinin B2 receptor antagonists in rats.

Bradykinin (BK) is a vasoactive peptide reputed to play an important role in cardiovascular homeostasis. In this study, we describe the cardiovascular changes (mean blood pressure (BP) and heart rate (HR)) induced by the i.v. administration (left jugular vein) of two selective kinin B2 receptor antagonist, namely icatibant (0.1-1 micromol/kg as a bolus) and MEN1 1270 (0.1-1 micromol/kg as a bolus or 1 micromol/kg infused in 15 or 60 min), in urethane-anaesthetized or conscious rats with an indwelling catheter implanted in the right carotid artery for BP measurements. In conscious rats, icatibant at 0.1 or 0.3 micromol/kg did not change BP but at 0.1 micromol/kg increased HR at 30 min from administration. MEN1 1270 at 0.1 or 0.3 micromol/kg induced a dose-related increase in BP and a concomitant bradycardia (significant at 0.3 micromol/kg) lasting for 5 or 30 min, respectively. Icatibant at 1 micromol/kg induced a slight (P < 0.05) increase in BP that resolved in 5 min and a biphasic tachycardia (peaks at 30 and 90 min from administration). MEN1 1270 at 1 micromol/kg induced a triphasic change in HR (tachycardia in the first 5 min, bradycardia at 30 min, and tachycardia at 90 and 120 min) and a biphasic change in BP (hypotension at 15 min and hypertension at 30 min). The i.v. infusion of MEN1 1270 (1 micromol/kg in 15 or 60 min) produced hypertension, whereas HR was increased only following the 15-min infusion. In urethane-anaesthetized rats, both icatibant and MEN1 1270 (0.1 micromol/kg as a bolus) increased BP and the onset for this effect was correlated with the time course of the antagonism of BK-induced hypotension, where the effect of MEN1 1270 was more rapid than that of icatibant. These results indicate that kinin B2 receptor antagonists can induce acute cardiovascular effects, and the reason for the different haemodynamic profile between icatibant and MEN1 1270 could be putatively attributed to kinetic characteristics.

High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: results of a randomized trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group.

PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.

Effect of a tachykinin NK(2) receptor antagonist, nepadutant, on cardiovascular and gastrointestinal function in rats and dogs.

The effect of the tachykinin NK(2) receptor antagonist, nepadutant (MEN 11420 or (c[[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta)])) was assessed on cardiovascular function (unanaesthetized rats and anaesthetized dogs) and gastrointestinal motor activity (fasted unanaesthetized dogs). The selective tachykinin NK(2) receptor agonist, [betaAla(8)]neurokinin A (4-10), up to 100 nmol/kg, i.v., did not produce changes on mean blood pressure or heart rate in unanaesthetized rats. Nepadutant did not affect blood pressure and heart rate up to 10 micromol/kg, whereas saredutant (SR 48968 or ((S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] benzamide), a nonpeptide antagonist, produced a transient reduction of mean blood pressure and heart rate. Nepadutant up to 20 micromol/kg, i.v. neither caused changes of cardiovascular and respiratory parameters in anaesthetized dogs nor induced any changes in left ventricular systolic pressure, left ventricular dP/dt or of electrocardiogram (lead II) waveforms. Intravenous administration of neurokinin A (9 nmol/kg) in unanaesthetized dogs stimulated gastrointestinal motility for 20-25 min. Nepadutant at 0.1 micromol/kg suppressed the stimulant effects of neurokinin A but, up to a dose of 10 micromol/kg, did not produce significant changes in the basal migrating motor complexes. We conclude that tachykinin NK(2) receptors do not participate in the physiologic regulation of resting cardiovascular and respiratory functions and that they do not regulate the fasted pattern of gastrointestinal motility. The cardiovascular changes induced by the nonpeptide tachykinin NK(2) receptor antagonist, saredutant, likely arise from nonspecific effects unrelated to tachykinin NK(2) receptor blockade.

The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer's disease.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43 non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut-off point for being considered as responsive to tacrine treatment was a 4-point decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers to respond better than the epsilon4+ carriers. When patients were stratified by gender, no differences were found between the effects of the treatment on men and women. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to tacrine in AD patients.

Relevance of aromatic residues in transmembrane segments V to VII for binding of peptide and nonpeptide antagonists to the human tachykinin NK(2) receptor.

We used membranes from Chinese hamster ovary cells stably transfected with the human tachykinin NK(2) receptor, either wild-type or mutated, at four aromatic residues (His(198), Tyr(266), Phe(270), Tyr(289)) located in transmembrane segments V to VII, to assess the role of these residues in the binding of natural tachykinins and peptide and nonpeptide antagonists. Three radioligands, the agonist [(125)I]neurokinin A (NKA), the peptide antagonist [(3)H]MEN 11420, and the nonpeptide antagonist [(3)H]SR 48968 bound to the wild-type receptor with high affinity (K(d) = 2.4 nM, 0.3 nM, and 4.0 nM, respectively). Four of the six mutant receptors tested retained high affinity for at least one of the radioligands. H(198)A mutation abrogated the binding of NKA but not that of MEN 11420 or SR 48968 (K(d) = 4.8 and 11.5 nM, respectively); Y(266)F mutation abrogated the binding of MEN 11420 but not that of NKA or SR 48968 (K(d) = 2.8 nM and 1.2 nM, respectively); F(270)A mutation abrogated the binding of both NKA and MEN 11420 but not that of SR 48968 (K(d) = 1.6 nM); Y(289)F mutation abrogated the binding of SR 48968 but not that of NKA and MEN 11420 (K(d) = 2.0 and 2.9 nM, respectively). Y(266)A and Y(289)A mutations abrogated the binding of all radioligands. Among the unlabeled antagonists, the affinity of the nonpeptide GR 159897, at variance with SR 48968, resulted heavily compromised by H(198)A and Y(266)F mutations; the peptide antagonists R396 and MEN 10376 essentially followed the binding profile of NKA, but R396 showed markedly increased affinity for the Y(289)F mutant receptor. Taken together, these results indicate that different, partially overlapping sets of sites may be involved in the binding of agonists and diverse antagonists to the human tachykinin NK(2) receptor.

Pharmacokinetics of the bicyclic peptide tachykinin NK2 receptor antagonist MEN 11420 (nepadutant) in rats.

The pharmacokinetics of MEN 11420 [nepadutant, c[[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta++ +)]], a potent glycosylated analogue of the selective, bicyclic peptide, tachykinin NK2 receptor antagonist MEN 10627 [c[(Met-Asp-Trp-Phe-Dpr-Leu)c(2beta-5beta)]], were studied in rats after different routes of administration. The plasma concentration profile for MEN 11420 after iv administration (1 mg/kg) was compared with that for the parent compound MEN 10627. The mean plasma half-life (44 min) and AUC value (285 micrograms.min/ml) for MEN 11420 were almost 3-fold greater than those for MEN 10627, and the systemic clearance was reduced to one third. The absolute bioavailability of MEN 11420 after intranasal (1 mg/kg) or ip (1 mg/kg) administration was virtually complete. However, bioavailability was only approximately 5% after intrarectal treatment (5 mg/kg) and was too low to be quantified (<3%) after sublingual (1 mg/kg) or oral (10 mg/kg) doses. The urinary excretion of unchanged compound, after an iv dose of 1 mg/kg, was approximately 34% of the dose for MEN 11420 but was <2% for MEN 10627. This is in agreement with in vitro data showing that MEN 11420 is more resistant to hydrolytic and oxidative metabolism than is MEN 10627. It is concluded that the hydrophilic modification of MEN 10627 to produce MEN 11420 resulted in marked improvement in the pharmacokinetic and metabolic characteristics of the peptide.

Characterization of [3H]MEN 11420, a novel glycosylated peptide antagonist radioligand of the tachykinin NK2 receptor.

[3H]MEN 11420, a radiolabeled glycosylated peptide antagonist of the tachykinin NK2 receptor, has been investigated in ligand-receptor binding assays using membranes of CHO cells transfected with the human tachykinin NK2 receptor. [3H]MEN 11420 bound to a single class of high affinity binding sites: its binding was inhibited by natural tachykinins (potency ranking: NKA >> SP > or = NKB), as well as by peptide (MEN 11420 > MEN 10376 >> R 396) and nonpeptide (SR 48968 > GR 159897) selective NK2 receptor antagonists. These data indicate that [3H]MEN 11420 is a potent radioligand for the human tachykinin NK2 receptor that may represent a useful tool for studying ligand-receptor interactions at the molecular level.

World Wide Web interface for advanced SPECT reconstruction algorithms implemented on a remote massively parallel computer.

Data from Single Photon Emission Computed Tomography (SPECT) studies are blurred by inevitable physical phenomena occurring during data acquisition. These errors may be compensated by means of reconstruction algorithms which take into account accurate physical models of the data acquisition procedure. Unfortunately, this approach involves high memory requirements as well as a high computational burden which cannot be afforded by the computer systems of SPECT acquisition devices. In this work the possibility of accessing High Performance Computing and Networking (HPCN) resources through a World Wide Web interface for the advanced reconstruction of SPECT data in a clinical environment was investigated. An iterative algorithm with an accurate model of the variable system response was ported on the Multiple Instruction Multiple Data (MIMD) parallel architecture of a Cray T3D massively parallel computer. The system was accessible even from low cost PC-based workstations through standard TCP/IP networking. A speedup factor of 148 was predicted by the benchmarks run on the Cray T3D. A complete brain study of 30 (64 x 64) slices was reconstructed from a set of 90 (64 x 64) projections with ten iterations of the conjugate gradients algorithm in 9 s which corresponds to an actual speed-up factor of 135. The technique was extended to a more accurate 3D modeling of the system response for a true 3D reconstruction of SPECT data; the reconstruction time of the same data set with this more accurate model was 5 min. This work demonstrates the possibility of exploiting remote HPCN resources from hospital sites by means of low cost workstations using standard communication protocols and an user-friendly WWW interface without particular problems for routine use.

Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer.

PURPOSE: Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity. PATIENTS AND METHODS: One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units. RESULTS: One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms. CONCLUSION: Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.

Effect of adjuvant chemotherapy with or without anthracyclines on the activity and efficacy of first-line cyclophosphamide, epidoxorubicin, and fluorouracil in patients with metastatic breast cancer.

PURPOSE: To evaluate the effect of previous adjuvant chemotherapy with or without anthracyclines on overall survival (OS), progression-free survival (PFS), and objective response (OR) rates of metastatic breast cancer patients treated with cyclophosphamide, epidoxorubicin, and fluorouracil (CEF) as first-line chemotherapy. PATIENTS AND METHODS: Three-hundred twenty-six assessable metastatic breast cancer patients entered onto four consecutive randomized trials performed in our Institution and North-West Oncology Group (GONO) cooperative centers from 1983 to 1994. Patients received CEF-based chemotherapy as first-line therapy and were then evaluated. One hundred forty-four patients (44%) did not receive previous adjuvant chemotherapy, and 143 (44%) and 39 (12%) patients received cyclophosphamide, methotrexate, and fluorouracil (CMF)-based and anthracycline-based adjuvant chemotherapy, respectively. RESULTS: ORs to CEF chemotherapy were observed in 161 patients (49.4%). On univariate analysis, patients who had received prior adjuvant chemotherapy had a significantly lower probability of response than patients who did not: 43% versus 58% (P=.02). No difference between CMF-based (OR rate, 43%) and anthracycline-based (OR rate, 44%) adjuvant chemotherapy was observed. Stepwise logistic regression analysis indicated that adjuvant chemotherapy (P=.005), bone as dominant metastatic site (P=.02), and previous hormonotherapy for metastatic disease (P=.005) were the most important factors in predicting a poor OR rate. The median PFS and OS times of the whole group were 9.8 and 17.9 months, respectively. Patients who did not receive adjuvant chemotherapy had a longer survival time (21.1 months) compared with patients previously treated with CMF-based (15.3 months) or anthracycline-based (15.8 months) adjuvant chemotherapy. Multivariate analysis confirmed adjuvant chemotherapy to be among the strongest prognostic factors associated with both a poor PFS and OS. CONCLUSION: Previous adjuvant chemotherapy adversely affects OR, PFS, and OS in metastatic breast cancer patients treated with the CEF regimen as first-line chemotherapy. No difference was observed between patients previously treated with CMF-based or anthracycline-based adjuvant chemotherapy.

Maternal uniparental disomy for chromosome 14.

A girl carrying a de novo balanced 13-14 robertsonian translocation showed a clinical phenotype with severe hypotonia, hyperextensible joints, frontal bossing, asymmetric face, no mental retardation, severe scoliosis and motor delay. In situ hybridization analysis on chromosome spreads revealed the presence of the two centromeres in the rearranged chromosomes. Molecular analysis on genomic DNA showed the presence in the proposita of two chromosomes 14 of maternal origin and no chromosome 14 from the father indicating a maternal monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows several similarities with other reported cases of mUPD14, suggesting imprinting of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.

Pharmacology of LR-B/057, a novel orally active AT1 receptor antagonist.

We studied the pharmacologic properties of LR-B/057, a novel nonpeptide angiotensin II (AII) receptor antagonist. The compound potently displaced [3H]AII from AT1 but not from AT2 receptors in rat adrenal cortex (Ki 3 nM), but did not modify the dissociation rate of the radioligand from the receptors. Both its affinity and the nature of its interaction with AT1 receptors (saturation studies) were markedly affected by the presence of bovine serum albumin (BSA) in the binding assay. In rabbit aorta, LR-B/057 caused nonparallel shifts to the right of the dose-response curve to AII and decreased the maximal response (pKB 9.6). Oral (p.o.) administration of LR-B/057 to conscious rats dose-dependently antagonized the pressor response to AII. LR-B/057 administered either intravenously (i.v.) or p.o. to conscious renal hypertensive rats produced a powerful dose-dependent antihypertensive effect. These results show that LR-B/057 is a potent and selective antagonist at AT1 receptors and has p.o. bioavailability.