Gene symbol: Notch3. Disease: CADASIL.
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Amino Acid Substitution↗
Biomedical subjects
S Bianchi
Publications and source records attributed to S Bianchi.
A supernova origin for dust in a high-redshift quasar.
Interstellar dust plays a crucial role in the evolution of the Universe by assisting the formation of molecules, by triggering the formation of the first low-mass stars, and by absorbing stellar ultraviolet-optical light and subsequently re-emitting it at infrared/millimetre wavelengths. Dust is thought to be produced predominantly in the envelopes of evolved (age >1 Gyr), low-mass stars. This picture has, however, recently been brought into question by the discovery of large masses of dust in the host galaxies of quasars at redshift z > 6, when the age of the Universe was less than 1 Gyr. Theoretical studies, corroborated by observations of nearby supernova remnants, have suggested that supernovae provide a fast and efficient dust formation environment in the early Universe. Here we report infrared observations of a quasar at redshift 6.2, which are used to obtain directly its dust extinction curve. We then show that such a curve is in excellent agreement with supernova dust models. This result demonstrates a supernova origin for dust in this high-redshift quasar, from which we infer that most of the dust at high redshifts probably has the same origin.
Journal Article↗
Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.
To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.
Breast Neoplasms↗
Occupational therapy and tools for monitoring the effectiveness of therapy.
We have constructed a battery of tests for assessment of some aspects of self-sufficiency (washing, dressing, eating) and called it the Ronchi brief evaluation battery (RBEB). The tests were designed to allow for more accurate monitoring of the effects of occupational therapy interventions with patients recovering in our subacute care nursing home (abbreviated from the Italian name: "Residenza Sanitaria Assistenziale" as RSA). The RBEB results showed great advantage, in maximizing levels of independence of patients, of occupational therapy input. Furthermore, when RBEB results are compared to those from the Barthel index, greater improvements are seen in each of the functions tested suggesting that the RBEB results are more detailed and therefore more appropriate. The RBEB tests are based on analysis of the activities of daily living (ADL) and have provided us with brief, clear, accurate, low-cost and practical baseline assessment and review tool.
Activities of Daily Living↗
Two cases of meningeal involvement in Wegener's granulomatosis.
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Female↗
Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.
Aged↗
Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.
AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.
Biomarkers, Tumor↗
Cell response to oxidative stress induced apoptosis in patients with Leber's hereditary optic neuropathy.
OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease in which acute or subacute bilateral visual loss occurs preferentially in young men. Over 95% of LHON cases are associated with one of three mitochondrial DNA (mtDNA) point mutations, but only 50% of men and 10% of women who harbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete penetrance and preference for men suggests that additional genetic (nuclear or mitochondrial) and/or environmental factors must modulate phenotype expression in LHON. A role for reactive oxygen species (ROS) in mitochondrial diseases, secondary to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpose of this study was to investigate the role of oxidative stress induced apoptosis in LHON. METHODS: The 2-deoxy-D-ribose induced apoptotic response of peripheral blood lymphocytes from six patients with LHON and six healthy subjects was investigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential. RESULTS: Cells of patients with LHON had a higher rate of apoptosis than those of controls and there was evidence of mitochondrial involvement in the activation of the apoptotic cascade. CONCLUSIONS: These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expression of genetic mutations in different individuals and could represent a potential target in the development of new therapeutic strategies.
Antimetabolites↗
Measurement of somatostatin receptor subtype 2 mRNA in breast cancer and corresponding normal tissue.
Somatostatin analogs are effective in inhibiting growth of human breast cancer cell lines. These antiproliferative effects are mediated by specific receptors located on cell membranes. The somatostatin receptor subtype 2 (sst2) is the principal mediator of somatostatin effects in normal and cancer cells, and its presence has already been demonstrated in breast cancer. The purpose of our study was to evaluate the clinical relevance of the expression of sst2 by quantifying its mRNA in a large group of infiltrating breast cancers and their corresponding normal tissues. The expression of sst2 mRNA was measured with quantitative real time RT-PCR in 169 breast cancers and in their corresponding unaffected tissues. We evaluated the association of sst2 expression with the commonest clinical-pathologic features of breast cancer. The correlation with a marker of cell proliferation (Ki-67) and with receptor concentration was also evaluated. In cancer tissues, we found that the absolute concentrations of sst2 mRNA were significantly higher in estrogen receptor (ER)-positive samples (P=0.002) as well as in lymph-node-negative cancers (P=0.04) (Student's t-test or one-way ANOVA). In addition, sst2 mRNA was significantly higher in breast cancers than in corresponding unaffected tissues (P=0.0002). However, when the clinical-pathologic parameters were considered, this gradient maintained its statistical significance only in tumors expressing positive prognostic markers, such as the presence of ER (P=0.0005) and progesterone receptors (PgR) (P=0005), and the lack of lymph-node involvement (P=0.0003). The same difference was also significant in postmenopausal women (P=0.001) and in T1 patients (P=0.001). In addition, sst2 mRNA expression was significantly higher (P=0.008) in low-proliferating breast cancers. Finally, we found that the quantitative expression of sst2 mRNA was directly related to the PgR concentration in breast cancer tissues (P<0.001). Our data seem to indicate that an upregulation of sst2 gene expression is a common feature of breast cancers which, on the basis of conventional predictive parameters, are expected to have a better prognosis. Featuring a possible role of somatostatin analogs in combined endocrine therapies for breast cancer, our results seem to confirm that the sst2 status of the tumor should be previously investigated.
Adult↗
[Sonography of the hand and wrist].
In the recent years US has gained wide diffusion as a useful imaging tool in the evaluation of musculoskeletal disorders. Recognized advantages of US over the other imaging modalities are low costs, non-invasiveness, possibility to perform a dynamic examination and readiness. Unfortunately, US has a long learning curve and allows good results only when performed by well-trained and experienced examiners. Specifically, utilization of the recent small transducers allows to perform dynamic examination of the hand during flexion-extension movements of the fingers, while their high frequency (till 15 MHz) have increased the possibility to evaluate small anatomic structures of the hand and wrist as well as to detect subtle pathologic changes. The purpose of this article is to present first the normal basic anatomy and US appearance. Then the main pathological conditions including joint and tendon disorders, foreign bodies and other traumatic lesions, entrapment neuropathies and expansible lesions will be presented.
Arthritis, Rheumatoid↗
[Ultrasonography of peripheral nerves].
With the recent advances in broadband transducer technology and refinements in scanning technique, an increasing number of nerves and related pathologic conditions are identified with sonography. High-resolution sonography can support clinical and electrophysiological testing for detection of a variety of nerve abnormalities, including entrapment neuropathies, traumas, infectious disorders, and tumors. In addition, procedures of regional anesthesia and percutaneous treatment of painful neuromas can be effectively guided by sonography in real time. This article addresses the normal US appearance of peripheral nerves and discusses the potential role of this technique to image nerve disorders in specific clinical settings.
Animals↗
Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.
Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.
Breast Neoplasms↗
Silent ischemia is more prevalent among hypertensive patients with microalbuminuria and salt sensitivity.
Some patients with essential hypertension manifest greater than normal urinary albumin excretion (UAE). Salt-sensitive hypertensives also manifest greater UAE compared to salt-resistant individuals. Although the significance of these associations is not well established, several lines of evidence suggest that microalbuminuria and/or salt sensitivity may be associated with greater prevalence of cardiovascular risks and events. In this study, we have evaluated by ergometric exercise 42 subjects with microalbuminuria and 42 matched individuals with normal UAE. All these subjects also underwent a standardized protocol to determine blood pressure sensitivity to a high salt intake. Patients with microalbuminuria displayed greater levels of ambulatory blood pressure and a greater rise in systolic blood pressure during exercise compared to patients with normal UAE (33.1 +/- 1.56 vs 26.4 +/- 1.7 mmHg, P < 0.001). Seven hypertensive patients with microalbuminuria developed ST segment depression during exercise compared to only one subject with normal UAE. Salt-sensitive patients manifested greater UAE than salt-resistant subjects (58 and 14 mg, 24 h, P < 0.001) and greater prevalence of silent ischemia (6 vs 2) than salt-resistant individuals. In conclusion, these studies have shown that hypertensive individuals with microalbuminuria and/or salt sensitivity manifest an increased prevalence of silent ischemia.
Albuminuria↗
Evidence of apoptosis via TUNEL staining in muscle biopsy from patients with mitochondrial encephaloneuromyopathies.
Apoptosis is an evolution-conserved form of cell death essential for development and maintenance of tissue homeostasis. Dysregulation of apoptosis has been implicated in several pathological conditions, including neurodegenerative disorders. The crucial role of mitochondria in regulation of the apoptotic pathway prompted us to investigate the pattern of apoptosis in muscle biopsies from 17 patients with mitochondrial encephaloneuromyopathies caused by mtDNA defects. The results were compared with muscle biopsies from controls and from patients with myopathies without mitochondrial impairment. The terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling (TUNEL) reaction was used as marker of apoptosis. Our findings were very heterogeneous, even between patients with the same mtDNA mutations, suggesting that tissue evaluation of apoptotic process is less useful than in vitro techniques, for investigating the role of apoptosis in mitochondrial pathologies.
Adult↗
Quantification of the effect of mammographic screening on fatal breast cancers: The Florence Programme 1990-96.
Breast cancer cases diagnosed in women aged 50-69 since 1990 to 1996 in the City of Florence were partitioned into those who had been invited to screening prior to diagnosis and those who had not. All cases were followed up for vital status until 31 December 1999. The cumulative number of breast cancer deaths among the cases were divided by screening and invitation status, to give the rates of cancers proving fatal within a period of 8 years of observation (incidence-based mortality). We used the incidence-based mortality rates for two periods (1985-86, 1990-96), pre and during screening. The incidence-based mortality ratio comparing 1990-96 and 1985-86 was 0.50 (95% CI : 0.38-0.66), a significant 50% reduction. For noninvited women, compared to 1985-86, there was a 41% significant mortality reduction (RR=0.59, 95% CI : 0.42-0.82). The comparable reduction in those invited was a significant 55% (RR=0.45, 95% CI : 0.32-0.61). The incidence ratio of rates of cancers stage II or worse was close to one when the noninvited in 1990-96 were compared with 1985-86 (RR=0.97, 95% CI : 0.78-1.21). Excluding prevalent cases, the rate of stage II+ breast cancer cases was 42% lower in Screened women compared with the noninvited (RR=0.58, 95% CI : 0.45-0.74). This study confirmed that new treatments and the first rounds of the screening programme contributed to reducing mortality from breast cancer.
Aged↗
Pelvic haemophilic pseudotumour: management of a patient with high level of inhibitors.
Haemophilic pseudotumour (HP) is a rare but very serious complication of haemophilia. HP affects mainly patients with severe haemophilia and those who have developed antibodies to factor VIII or factor IX. We report on a 45-year-old man with haemophilia A and high titres of inhibitors who developed an extensive HP with progressive destruction of the right ilium over a period of 12 years. The different therapeutic options (conservative management by replacement therapy, surgical approach, radiotherapy, percutaneous evacuation with secondary refilled cavity and transcatheter arterial embolization) are reviewed.
Bone Diseases↗
Secondary omental torsion in children: report of two cases and review of the literature.
Torsion of the greater omentum (TGO) may be due to a congenital abnormal attachment of its free edge. There are no specific symptoms that allow a preoperative differential diagnosis of this condition from common pathologies such as acute appendicitis. Attachment of the omentum to the large bowel and the absence of concomitant diseases make it possible to distinguish TGO secondary to a congenital attachment anomaly from omental infarction, primary TGO, and TGO secondary to an acquired attachment anomaly (attachment to cysts, tumours, hernias, surgical scars, or perforated bowel segments). Resection of the ischaemic portion of the omentum permits complete resolution of the clinical symptoms. The authors report two cases of TGO in children due to abnormal attachment of the greater omentum to the ascending and transverse colon, respectively.
Adolescent↗
Assessment of the early impact of the population-based breast cancer screening programme in Florence (Italy) using mortality and surrogate measures.
The aim of this study was to evaluate the effects by the end of 1999 of the Florence breast screening programme that started in 1990. Approximately 60000 women (aged 50-69 years) were enrolled from 1990 to 1993. Breast cancer cases diagnosed from 1990 to 1996 were partitioned by the method of detection, classified by their tumour size and nodal status and followed-up for mortality at on the 31 December 1999. Incidence-based mortality in the 50-74-year-old women and advanced carcinomas rates were assessed. Due to low compliance (approximately 60%) and the long enrollment phase, only approximately 35% of the total age-specific population person-years were screened. The number of invasive cases diagnosed was 1122, 17% higher than the 958 expected. After the prevalence screening, a reduction of approximately a quarter in advanced carcinomas was observed in the invited women (Odds Ratio (OR): 0.74; 95% Confidence Interval (CI): 0.55-0.98). In the period 1990-1999, 547 breast cancer deaths were observed: 78 (14%) occurred in women invited and half of these in never responders, 385 (70%) occurred in cases diagnosed before screening started. Disproportionate numbers of deaths occurred in women with advanced tumours. The 19% mortality reduction for the invited women was of borderline statistical significance (observed/expected (O/E) deaths: 0.81; 95% CI: 0.64-1.01); by a one-sided test the result would be unequivocally significant. The mortality reduction attributable to screening in the whole population over the 10-year period was 3.2%. The incidence-based mortality analysis confirmed the current follow-up time is too short for screening to have had a major effect on the breast cancer mortality trends. Screening performance might be improved by a higher level of compliance and shorter interval times, but the estimate of the mortality reduction for the invited and the lower rate of advanced carcinomas confirmed that the effect of the programme is in the expected direction.
Aged↗