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.

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.

[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.

[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.

Effects of therapeutic doses of lactulose vs. polyethylene glycol on isotopic colonic transit.

BACKGROUND: Lactulose and polyethylene glycol are osmotic agents used to treat idiopathic chronic constipation. AIM: To compare the effects of low doses of lactulose and PEG 4000 on transit time measured by scintigraphy in normal subjects. METHODS: For 5 days, 10 healthy subjects received either 10 g b.d. of lactulose or PEG 4000 in a randomized, double-blind, crossover study. On the evening of day 4, they took a capsule containing Amberlite resin pellets labelled with (111)In. On day 5, after a 1000 kcal test meal labelled with 99 Tcm, gastric, small bowel and colonic transits were measured. RESULTS: Gastric emptying and small bowel transit time were not different. Ascending colon emptying curve was significantly accelerated with lactulose in comparison with polyethylene glycol (P = 0.001) and, respectively, 50 +/- 18% vs. 35 +/- 18% of the radioactivity had left the ascending colon at the end of the study (P < 0.05). The descending colon filling curves, variations in the geometric centre and numbers of scintigraphic movements were not different. CONCLUSIONS: In healthy subjects, in comparison to PEG 4000, usual therapeutic doses of lactulose significantly accelerate ascending colon emptying. This result supports a stimulating motor effect of colonic fermentation of lactulose.

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.

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.

[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.

[Lead poisoning in adults. Experience of the Poison Control Center of Marseille from 1993 to 2000]. / Le saturnisme des adultes. Expérience du Centre antipoison de Marseille de 1993 à 2000.

OBJECTIVE: Report the experience of the Marseille's anti-poison center with lead poisoning adults. PATIENTS AND METHODS: Between 1993 and 2000, 45 adults patients consulted the poison Centre of Marseille for a history of lead exposure (9 women, 36 men, average age 44 YO, between 22 an 76 YO). The lead sources were mostly occupational (welding, heavy metal industries...), but some were environmental (shooting as a hobby, hunting,...). RESULTS: Ninety-one percent of the patients presented with a clinical feature of possible lead intoxication (asthenia, abdominal pain, anaemia, seizures,...). For 22 patients, calcitetracemate provocation test was negative. 6 patients with a positive test refused to be treated. 16 patients with a positive test were treated with chelation therapy (average lead blood level 566 micrograms/l--mini 320 micrograms/l, maxi 943 micrograms/l--and average lead urine elimination 3,011 micrograms/24 H--mini 789 micrograms/24 H, maxi 7,229 micrograms/24 H. 58 cures were done (1 to 12 cures for each patient). The average quantities of lead eliminated in the urine during the chelation therapy was 30,912 micrograms +/- 29,059 micrograms by case. For 12 patients who stopped the lead exposure after the diagnosis of lead poisoning, the chelaion therapy permitted to decrease the lead blood level of 69%. For 4 patients still exposed during the treatment, the lead blood level decrease of 7% only. For the 16 treated patiEnts, a clinical improvement was noted, and no adverse effects of chelation therapy was observed during the 58 cures.

[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.

Mycoplasma genitalium in males with nongonococcal urethritis: prevalence and clinical efficacy of eradication.

BACKGROUND: Mycoplasma genitalium is regarded as a potential pathogen of the human urogenital tract based on prevalence findings of several European studies. GOAL: To determine the prevalence of M genitalium in urethral specimens of symptomatic patients with nongonococcal urethritis and from asymptomatic patients attending a sexually transmitted disease clinic in Milan, and to verify the clinical efficacy of M genitalium eradication by antibiotic treatment. STUDY DESIGN: From May 1998 to late April 1999, a routine analysis for M genitalium by DNA amplification (polymerase chain reaction) was performed in patients attending the Institute of Dermatological Science in Milan. The authors examined urethral swabs from 178 symptomatic and 23 asymptomatic males. M genitalium-positive patients were clinically and microbiologically tested after treatment with either doxycycline or azithromycin. RESULTS: Among males with nongonococcal urethritis, M genitalium was detected in 14.0% of patients as the only agent; in 15.1% of patients in association with Chlamydia trachomatis and/or Ureaplasma urealyticum; and in 1 asymptomatic patient. In all symptomatic M genitalium-positive patients, antibiotic treatment eradicated the infection and cured clinical symptoms. CONCLUSION: These data reveal the high prevalence of M genitalium in symptomatic patients, the rarity of asymptomatic carriers, the high susceptibility to antibiotic treatment, and the clinical efficacy of M genitalium eradication. Moreover, data confirm the etiologic role of M genitalium in inflammatory processes of the human urogenital tract in the Mediterranean area.