Breast density in NF1 women: a retrospective study.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.

[Exposure to vegetal esters based metal cutting fluids: health effects]. / Esposizione ad oli lubrorefrigeranti vegetali: effetti sulla salute.

The aim of our research is to study respiratory and dermatologic diseases (irritative and allergic) in a cohort of workers exposed to vegetal esters based metal cutting fluids of the latest generation. A cohort of 81 workers (mean age 34.5 years, seniority 17.4 years), with mean exposure to vegetal esters based metal cutting fluids of 2.8 years, has been subjected to clinical evaluations. The investigation did not reveal any disease or disorder of the respiratory system, any folluculitis or any allergic contact dermatitis caused by sensitization to vegetal esters based metal cutting fluids. On the contrary we documented 5 cases of irritant contact dermatitis, even if favored by an improper use of protection devices. According to early results, the introduction of vegetal esters based metal cutting fluids seems to reduce the risk to the worker's health. A longitudinal surveillance is still needed to confirm that even in the medium and long-term sensitizations will not occur.

Characterization of the HER2 status in BRCA-mutated breast cancer: a single institutional series and systematic review with pooled analysis.

BACKGROUND: Pathogenic variants (PVs) in BRCA1/2 genes account for ∼6% of breast and 20% of ovarian cancers. Most breast tumors developed by BRCA1 carriers are triple negative. BRCA2 tumors have similar rates of estrogen receptor positivity as sporadic controls but are less likely to be human epidermal growth factor receptor 2 (HER2)-positive. Prevalence of HER2 positivity among breast cancers (BCs) in BRCA1/2 mutation carriers is poorly and variably described, ranging from 0% to 10% and 0% to 13% in BRCA1 and BRCA2 carriers, respectively. PATIENTS AND METHODS: We assessed the prevalence of HER2 positivity among a single institutional cohort of 398 BCs developed in carriers of BRCA1/2 PVs (240 BRCA1, 158 BRCA2). Subsequently, a systematic review of the literature and pooled analysis was carried out. RESULTS: In our series we found a 7% HER2 positivity rate among all first BRCA1/2 BCs overall. In BRCA1 carriers, 5.4% of BCs were HER2-positive compared with 9.5% in BRCA2-mutated patients. Among bilateral BCs, HER2-positive cases were 15.2% in the BRCA1 group and 23.1% in the BRCA2 group. Notably, six BRCA1 and eight BRCA2 carriers showed discordant HER2 status between BC and bilateral BC (23.7%, 14/59). The systematic review included 21 083 BRCA1/2 patients from 73 eligible studies. The pooled rate of BRCAmut/HER2-positive BCs is 9.1% (95% confidence interval 7.3% to 11.2%). BRCA1 and BRCA2 when reported as separate data ranged from 0% to 33.3% (mean 8.3%) and from 0% to 86% (mean 10.3%), respectively. CONCLUSIONS: As compared with sporadic cases, BCs occurring in BRCA1 and/or BRCA2 PVs carriers are less frequently HER2-positive. Prevalence of HER2 positivity in our series was consistent with pooled analysis and did not exceed 10%. Although not common, co-existence of BRCA mutations and HER2 overexpression and/or gene amplification should be acknowledged. More research is needed to better characterize this subgroup of patients who should not be excluded a priori from clinical trials of targeted therapy for BRCA1/2-driven cancers.

[Basic concepts of radiology physics]. / Bases physiques du radiodiagnostic.

An x-ray tube mainly emits low-energy X-rays, with few maximum energy E0 (equal in keV to the voltage U in kV) x-rays. Aluminium filtration (mandatory minimum thickness of 1.5 to 2.5 mm based on tube voltage) reduces soft X-rays and provides a mean energy equal to 2/3 E0. The half value layer of a reference material characterizes the spectrum. X-ray attenuation in tissues is due to secondary electron interactions: photoelectric effect at low-energy, especially in dense materials with high Z number; compton effect at intermediate-energy, proportional to density. The optimization of acquisition parameters of a medically necessary examination is based on appropriate selection of the highest voltage (U in kV) providing the best contrast and lowest tube current (Q in mAs) providing a diagnostic image.

[Concepts of dosimetry]. / Notions de dosimétrie.

The effects of exposure to ionizing radiation are determined by the absorbed dose D. The equivalent dose H takes into consideration the variation in probability of a stochastic effect (cancer, leukemia, genetic mutation) based on the quality of the exposure. The effective dose E takes into account the sensitivity of tissues (T) to stochastic effects from radiation exposure. Optimization of radiation exposure to patients in diagnostic radiology in based on diagnostic reference levels (DRL): entrance surface dose or dose-area product for conventional radiology; CT dose index and DLP for CT.

Feasibility study for a microchip-based approach for noninvasive prenatal diagnosis of genetic diseases.

Fetal DNA in maternal plasma may represent a source of genetic material for prenatal noninvasive diagnosis of genetic diseases. We evaluated a cohort of physiological pregnancies to determine if fetal DNA can be retrieved at any gestational week in sufficient quantity to be analyzed with advanced mutation detection technologies. We performed fetal DNA quantification by real-time polymerase chain reaction (PCR) on the SRY gene in 356 women sampled from 6 to 40 gestational weeks. Fetal DNA was retrieved at any week. All female fetuses were correctly identified. In 5 of 188 (2.6%) male-bearing pregnancies, no amplification was obtained. For noninvasive testing, complete clearance of fetal DNA after delivery is mandatory. Long-term persistence was not detected in women with previous sons or abortions. These findings confirm that maternal plasma may represent the optimal source of fetal genetic material. For noninvasive diagnosis of genetic diseases, we evaluated microchip technology. The detection limit for a minority allele determined by diluting a mutated DNA into a wild-type plasma sample was 5 genome equivalents, indicating that the test might be applied to the identification of paternally inherited fetal alleles in maternal plasma. The addition of peptide nucleic acids (PNAs) to either the PCR reaction or the chip hybridization mixture allowed approximately 50% inhibition of wild-type allele signals.

What is the pathogenetic role of antiphospholipid antibodies?

The association between antiphospholipid antibodies (aPL) and arterial or venous thrombosis, fetal loss and thrombocytopenia defines the so-called "antiphospholipid syndrome" (APS). Despite serial studies in recent years, a clear pathogenetic mechanism(s) has not yet been demonstrated. Several authors have investigated the interaction between aPL and the membranes of blood cells (endothelial cells and platelets) involved in coagulation. aPL is also thought to affect the balance between the procoagulant and anticoagulant states by interacting with plasma or tissue cofactors. Finally, the strong association between aPL and experimental animal models of fetal loss supports a direct pathogenetic role for aPL in inducing a poor pregnancy outcome in APS women.

Comparison of jet and ultrasonic nebulizers for alveolar targeting of methylprednisolone.

The secondary systemic effects of oral corticosteroid therapy in chronic lung disease indicate the possible benefits of local therapy. The aim of this study was to show if alveolar targeting of a corticosteroid, methylprednisolone (MP), is possible, and to determine which type of nebulizer allows the most selective deposition into the alveoli. A jet nebulizer (Respirgard II) with 2 ml volume fill (R2), and an ultrasonic nebulizer (Ultraneb 99) with 4 ml volume fill (U4), were compared using a 40-mg dose of MP labelled 99Tcm human serum albumin. Particle size and MP-to-albumin binding were measured in the aerosol cloud. Each nebulizer was used in random order in five healthy volunteers. A dynamic posterior scan of 68 images of 15 s each was performed with a Gammatome II gamma camera during inhalation. Peripheral and central regions of interest were automatically defined with reproducible methods, and the peripheral-to-central ratio was used as a penetration index. Stomach and oropharynx activities were estimated on static anterior and static left lateral views, respectively, at the end of the examination. The mass median aerodynamic diameter (MMAD) was lower for R2 when unlabelled MP was used. The MMAD of MP+HSA was compatible with alveolar targeting. In the aerosol cloud, MP-albumin binding was 75% for R2 and 79% for U4. Peripheral and central activities at equilibrium (13-16 min) were higher with U4, but the penetration index was significantly higher with R2. Moreover, the stomach and oropharynx activities were significantly lower with R2.(ABSTRACT TRUNCATED AT 250 WORDS)

Thalidomide treatment for hypertrophic cutaneous lupus erythematosus.

INTRODUCTION: In recent years numerous reports have been published regarding satisfactory thalidomide therapy for refractory chronic cutaneous lesions of lupus erythematosus (CCLE); to date, in the literature, there is just one report describing two patients affected by hyperkeratotic CCLE successfully treated with thalidomide. METHODS: Six patients affected by a hypertrophic/verrucous variant of CCLE were treated with thalidomide during the period October 1999 to December 2002 and their medical records were retrospectively reviewed. The initial dose of thalidomide was 100 mg/die by mouth for all the cases, while the duration of therapy was variable among the patients. RESULTS: All six patients responded to treatment: two had partial resolution of the lesions and four achieved almost complete clearing of cutaneous disease. Response to treatment was seen in the first month of therapy in all the patients. Follow-up nerve conduction studies were negative but a patient had to discontinue the drug because of neurological problems. DISCUSSION/CONCLUSION: Our case series confirms the efficacy of a 'low-dose' thalidomide regimen in verrucous/hyperkeratotic CCLE, which is normally unresponsive to conventional treatment; in this setting, thalidomide should be kept in mind as an extremely valid therapeutic option despite the lack of prospective, randomized, double-blind, placebo-controlled studies.

A rare case of pancreatic lipoma.

During CT scanning, a pancreatic lipoma was diagnosed in a 70 year-old woman presenting with abdominal pain, elevated amylase and abnormal liver function tests. The patient underwent surgical excision of the lipoma located in the head of the pancreas. The postoperative course was uneventful. This is the third case of pancreatic lipoma described in the literature. It is a very rare neoplasm that should be included in the category of "non-ductal" tumors of the pancreas. The role of different diagnostic tools for the differential diagnosis of ductal pancreatic adenocarcinoma is discussed.

[Measurement by isotope study of the cardiac output in the elderly]. / Mesure par étude isotopique du débit cardiaque chez le vieillard.

Cardiac output and haemodynamic volumetric values (stroke volume, stroke index, left ventricular end-diastolic volume, blood volume, mean corpuscular volume and packed red cell volume) were measured in a population of 69 very old subjects (80 to 102 years) whose heart was regarded as normal on the basis of criteria determined, by radiocardiography and radionuclide ventriculography. These harmless and non-invasive techniques provided reference values in subjects of a seldom explored age group. Altogether, these values were lower than those of younger adults, and they decreased with age. Their reliability is due to the fact that they were obtained by true measurement and not by extrapolation of results observed in adults.

[Dynamic study of the coronary vascular bed by selective coronary scanning using hyperaemia]. / Exploration dynamique du lit artériolaire coronaire par scintigraphie coronarienne sélective sous hyperhémie.

Advantage may be taken of the hyperaemic response to the iodine contained in the contrast medium injected during coronary angiography to assess the functional value of the coronary tree using radioactive microspheres. This series comprises 73 selective coronary scans performed in the resting state (113 m In marked microspheres) and during the hyperaemic phase (99 m TC marked microspheres) in 70 patients. A positive hyperaemic response distal to severe truncular stenosis indicates a good distal arteriolar bed and collateral circulation for aorto-coronary bypass grafting. After aorto-coronary bypass (23 cases), the hyperaemic response gives an indication of the functional value of the revascularised myocardium. In 71% cases, the results correlate well with the measurement of the peroperative blood flow through the graft. It is usually positive when the bypass graft is implanted with good distal arterial run off.

[Induced coronary spasm: immediate revascularization by the opposite coronary artery. Use of myocardial scintigraphy]. / Spasme coronaire provoqué revascularisation immédiate par suppléance hétérocoronarienne. Apport de la scintigraphie myocardique.

The case reported analyses the instantaneous revascularisation distal to a coronary spasm by electrocardiography and thallium scintigraphy. The patient, a 48 year old man, had an 18 months history of spontaneous anginal chest pain sensitive to trinitrin. No electrocardiogrammes had been recorded during an attack. Coronary angiography was normal apart from a slight reduction in calibre of a dominant right coronary artery. Injection of 0.4 mg methylergometrine provoked an occlusive spasm of this artery after 4 minutes. At the same time the patient experienced angina and 4,5 mm depression of the ST segment, without ST changes in D3 and AVF, was observed. Opacification of the left coronary artery during spasme of the right showed retrograde revascularisation of the posterior interventricular artery which was reversed when the coronary spasm was terminated with trinitrin. Thallium scintigraphy was performed during another spasm provocation test four days later which gave identical clinical and electrical changes. A zone of hypofixation with blurred limits over the inferior myocardial wall was demonstrated. In the absence of ST elevation and of lacuna on myocardial scanning, the myocardial ischaemia induced by this occlusive spasm could not be considered to be total. Therefore the immediate revascularisation of the coronary artery in spasm seemed to have played the role of an effective collateral circulation.

[Use of radiotherapy in cardiovascular disease. Radiophysical basis, current results, indications and perspectives]. / La curiethérapie en pathologie cardiovasculaire. Bases radiophysiques, résultats actuels, indications et perspectives.

Restenosis is the main limitation of percutaneous angioplasty, especially in vessels of small diameters such as the coronary arteries, the femoro-popliteal and tibial-peroneal arteries and the arterio-venous dialysis grafts. The extensive use of tents has not entirely prevented its occurrence, whereas treating in-stent restenosis gives even more uncertain results. Endovascular radiotherapy has emerged over the past few years as a promising approach to both prevent and cure it. The analogy between the tumour-like cellular proliferations observed in post-angioplasty restenosis and tumour processes prompted pioneering works to study the effect of ionizing radiations in animal models of arterial restenosis. The demonstrated feasibility, tolerance and efficacy of this approach lead to test this strategy in humans. The results of 3 recently presented randomized double-blind trials in the treatment of coronary in-stent restenosis have been so promising that endovascular brachytherapy might now be considered the treatment of choice in this indication. Other randomized trials are currently carried out to test whether endovascular brachytherapy may prevent restenosis in coronary and femoro-popliteal arteries as well as in hemodialysis shunts. In the present review, we describe the basics of the biological effects of ionizing radiations, the technical modalities to deliver endovascular radiations, our current knowledge about their effects on the vascular wall and the restenosis mechanisms, and the results of the first clinical studies. Finally, we address the remaining problems in the use of endovascular curietherapy and question the promises and challenges of its clinical application.

[Selective coronary scintigraphy using labelled microspheres]. / Scintigraphie coronarienne sélective au moyen de microsphères marquées

Selective intracoronary injection of microspheres labelled with radioactive substances which emit gamma rays with different energy levels (Indium 113 m and Technetium 99 m) allows us to explore by scintigraphic methods the areas of distribution of the two coronary arteries. Having been carefully calibrated, the particles are injected in limited numbers, and block the precapillary arterioles, where they gradually diminish in number. Scintigraphic examination is carried out in various projections (anteroposterior, left anterior oblique and right anterior oblique) immediately after coronary arteriography. Coronary scintigraphy allows us to establish the integrity of the distribution network of a coronary trunk which appears normal on coronary arteriography, to visualise the diminution of flow caused by a stenosed but patent trunk, and to visualise the extent of the collateral circulation and the quality of revascularisation achieved by an aorto-coronary bypass operation.

[Gynaecological pelvic mass. Emergency clinical assessment]. / Le tumefazioni ginecologiche dello scavo pelvico. Atteggiamento clinico in urgenza.

BACKGROUND: The authors report the gynaecological pathology of surgical interest occurring in an Emergency Department in the first half of 2000 and occasionally found during an operation in women who presented a pelvic mass or abdominal pain. METHODS: Six women, average age of 50 years, reached the Emergency Department: five of them were operated with an emergency procedure. RESULTS: Of the 6 cases, 1 patient was affected by uterine mass, 1 by uterine-ovarian mass and 3 by ovarian mass; in one patient, affected by ovarian tumour, another intervention was necessary for intestinal metastasis. CONCLUSIONS: The authors have considered the clinical aspect of the abdominal masses, the age of the patients, the diagnostic laboratory and instrumental implications, the surgical approach and the histological result, referring to literature. Their contribution is related to the need for an appropriate surgical approach in emergency where it may, sometimes, solve or, at least, stabilize an uncertain clinical case, thanks to the implicit basic knowledge of multidisciplinary surgical technique.

[Rupture of the urinary bladder caused by trivial trauma. Case report]. / Lo scoppio della vescica repleta da trauma banale. Contributo clinico.

The urinary bladder occupies the deep pelvic cavity and is well protected from the bacin: this is the reason why it can rarely be traumatized. Anyway it could suffer traumas, which can cause extraperitoneal and intraperitoneal ruptures. A classification of traumas that can injure the urinary bladder and the treatments of these lesions are presented. A clinical case personal observed regarding a 78 year-old female patient is described. An accidental fall and direct trauma in the hypogastrium caused a rupture of her urinary bladder. In this case, the patient was anuric, though the macrohematuria and microhematuria can be present in the 85% of the urinary bladder lesions. This is an interesting case since it deals with a urinary bladder wall rupture, due to a trivial trauma on the bladder.

[Role of pharmacovigilance center in information for the public on drugs. Experience in Marseille on 9 month]. / Rôle d'un centre de pharmacovigilance dans l'information du public sur le médicament. Expérience à Marseille sur 9 mois.

We analyzed the role of the Marseille pharmacovigilance center (working in collaboration with the local poison treatment center) in informing the general public on medicinal drugs. Over a 9-month period, the center received 115 requests from members of the public for information. 82.6% of callers were not members of the health professions and wanted information for themselves (61.7%, 67.6% women) or their children (26.08%). The questions mainly involved drug interactions (28.7%), side-effects (26%) and precautions for use in particular circumstances (20%). 178 proprietary drugs (47 of which had been bought over the counter) were mentioned. The main therapeutic classes were neuropsychiatric drugs (n = 41), cardiovascular drugs (n = 17) and analgesics (n = 16). A number of communication difficulties and problems of a deontological nature were encountered. Full information was provided in every case, together with advice on prevention to about half the callers.