Unpaved road conservation planning at the catchment scale.

In addition to soil losses on hillslopes, unpaved rural roads, especially when poorly designed and maintained, can be a significant contributor to the erosive processes seen at the catchment scale. In areas with deep soils, the solutions primarily focus on channeling excess surface runoff into settling ponds or terraces. However, few studies have addressed runoff control from roads on steep slopes in areas of shallow soil. Modeling hydrological processes at the catchment scale is a useful strategy for choosing the most effective and least costly conservation practices to control surface runoff. This study applies a mathematical model to a monitored catchment in southern Brazil to better understand the effects of conservation practices on unpaved roads and their impact on the hydrological and erosive dynamics of a small rural catchment. We calibrated the LISEM model using data from eight stormwater events and evaluated how three different road conservation scenarios-low (LI), medium (MI), and high intensity (HI)-contributed to sediment yield (SY), surface runoff volume (Qe), and peak flow (Qp) reduction. The LI and MI scenarios involved installation of hydraulic structures to control the road surface runoff (i.e. road ditch graveling, diversion weirs and grass waterways) while the HI scenario added surface runoff control practices (grass strips) to surrounding crop fields, in addition to the practices included in the MI scenario. Based on these scenarios, the results showed a Qe reduction at the catchment outlet from - 3.5% (LI) to - 22.5% (HI). The Qp and SY varied from + 6.0% (LI) to - 292.5% (HI) and from + 20.0% (LI) to - 963.9% (HI), respectively. These results show that the low- and medium-intensity practices were not effective in controlling surface runoff from roads, based on the Qe, Qb, and SY observed at the catchment's outlet. On the other hand, when MI scenarios were complemented with practices to control surface runoff in the cultivated areas, a significant reduction in surface runoff (Qe and Qp) and SY was verified.

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Manual thromboaspiration technique as a first approach for endovascular stroke treatment: A single-center experience.

BACKGROUND: For intracranial large vessel occlusion in acute ischemic stroke (AIS), a high degree of revascularization in the minimal amount of time predicts good outcomes. Recently, different studies have shown that the direct aspiration first pass technique (ADAPT technique) for AIS obtains high recanalization rates, fast interventions and low costs when it works as first attempt. This study retrospectively describes revascularization efficacy, duration of procedure, intra and post-procedural complications, early and after 90-days clinical outcome in a group of patients who underwent ADAPT as the primary endovascular approach, eventually followed by stent retriever thrombectomy, for recanalization of large vessels in the anterior circulation. MATERIALS AND METHODS: We analyzed clinical and procedural data of patients treated from April 2014 to August 2015. Recanalization was assessed according to the Thrombolysis in Cerebral Infarction score. Clinical outcome was evaluated at discharge and after 3 months (modified Rankin Scale, mRS). RESULTS: Overall, 71 patients (mean age of 69.7 years) were treated. Sites of occlusion were anterior circulation (including seven tandem extracranial-intracranial occlusions). In 39 patients i.v. rtPA was attempted. Recanalization of the target vessel was obtained in 87.3% of cases whereas direct aspiration alone was successful in 46/71cases (64.8%) with an average puncture-to-revascularization time of 43.1 minutes. Symptomatic intracranial hemorrhage occurred in 7.8% and embolization to new territories in 5.6%. In total, 38 patients (53.5%) had a good outcome at 90 days follow-up. CONCLUSIONS: In our series, the manual thromboaspiration technique has been shown as fast and safe, with good rates of vessel revascularization in 87.3% of patients and neurological outcome <3 mRS in 53.5% of patients.

Strain-specific pathogenicity of putative host-adapted and nonadapted strains of Streptococcus uberis in dairy cattle.

Streptococcus uberis is an important cause of intramammary infection in dairy cattle. Strains of Strep. uberis appear to differ in their ability to cause disease based on previous epidemiological studies. We explored the pathogenicity of 2 strains of Strep. uberis, where one strain represented a putatively host-adapted type based on its ability to cause persistent infection and to spread from cow to cow in a lactating herd. This type was part of a clonal complex that is commonly associated with bovine mastitis. The other strain, which was isolated from a transient infection in a single animal in the same herd and did not belong to any known clonal complex, was selected as putatively nonadapted type. Cows (6 per strain) were experimentally challenged in a single hind quarter and the adjacent hind quarter was used as mock challenged control quarter. Both strains showed an equal ability to grow in the milk of challenge animals in vitro. All cows that were challenged with the putatively host-adapted strain developed clinical signs of mastitis, including fever and milk yield depression as well as elevated somatic cell count due to influx of polymorphonuclear leucocytes and lymphocytes. The cytokine response followed a specific order, with an increase in IL-1ß, IL-6, and IL-8 levels at the time of first SCC elevation, followed by an increase in IL-10, IL-12p40, and tumor necrosis factor-α levels approximately 6h later. In 4 of 6 animals, IL-17A was detected in milk between 57 and 168 h postchallenge. The increase in IL-17A levels coincided with inversion of the prechallenge CD4(+)-to-CD8(+) T lymphocyte ratio, which was observed from 96 h postchallenge. This was followed by normalization of the CD4(+)-to-CD8(+) ratio due to continued increase of the CD8(+) concentration up to 312 h postchallenge. Spontaneous resolution of infection was observed in 5 animals and coincided with a measurable IL-17A response in 4 animals, suggesting that IL-17 may be involved in the resolution of intramammary infection. With the exception of minor elevation of IL-8 levels, no clinical, cytological, or immunological response was detected in quarters challenged with the nonadapted strain. The observed strain-specific pathogenicity was consistent across animals, implying that it is determined by pathogen factors rather than host factors.

Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: implications for ovarian cancer immunotherapy.

BACKGROUND: We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen. METHODS: We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix). Quantitative real-time PCR and immunohistochemistry staining techniques were used to validate microarray data at RNA and protein levels for SCGB2A1. Full-length human-recombinant SCGB2A1 was used to pulse monocyte-derived dendritic cells (DCs) to stimulate autologous SCGB2A1-specific cytotoxic T-lymphocyte (CTL) responses against chemo-naive and chemo-resistant autologous ovarian tumours. RESULTS: Gene expression profiling identified SCGB2A1 as a top differentially expressed gene in all histological ovarian cancer types tested. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody. Intracellular cytokine expression measured by flow cytometry showed a striking type 1 cytokine profile (i.e., high IFN-γ secretion) in SCGB2A1-specific CTLs. CONCLUSION: SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers and may represent a novel and attractive target for the immunotherapy of patients harbouring recurrent disease resistant to chemotherapy.

[Neuroimaging and definition of transient ischemic attack]. / Neuroimaging e definizione di attacco ischemico transitorio.

AIM: Transient ischemic attack (TIA) has to be considered an "alarm bell" of a more or less severe organic or systemic vasculopathy. Positive findings at neuroimaging means tissue damage. The purpose of this retrospective study was to assess the role of neuroimaging in the management of patients presenting with TIA, and to consider the relative implications. METHODS: In a consecutive series of 82 patients (53 males, 29 females, mean age: 65.9±13.1 years) admitted for TIA, it was possible to review the history and the clinical data of 66 patients, including ABCD2 score, laboratory including plasmatic D-dimer, and neuroimaging data including computed tomography (CT) and magnetic resonance imaging including diffusion-weighted with apparent diffusion coefficient measure (DWI-ADC) obtained at diagnosis and by a week later (16 by CT, and 50 by DWI-ADC). Thirty-three patients underwent DWI-ADC within 24 hours from symptoms onset. Statistical analysis has been performed by non-parametric tests (χ2 and Mann-Whitney), and logistic regression by a commercially available software. RESULTS: CT and/or DWI-ADC showed signs of acute ischemic lesions in 23/66 (35%) patients. 12 out of the 35 patients with a 24-hour DWI-ADC follow-up were positive. Statistical analysis showed that positive neuroimaging was significantly associated only with familial history of cardiovascular diseases (P<0.012) and previous TIA/stroke (P<0.046). CONCLUSION: In this patients series, at least 35% of patients with TIA had a positive neuroimaging, especially DWI-ADC. Positive neuroimaging seems an independent factor. Patients with TIA need an early assessment by neuroimaging including DWI-ADC, in order to obtain a correct classification and prognosis.

Relationship between the modified Rankin Scale and the Barthel Index in the process of functional recovery after stroke.

OBJECTIVE: The modified Rankin Scale (mRS) and the Barthel Index (BI) are the most common clinimetrical instruments for measuring disability after stroke. This study investigated the relationship between the BI and the mRS at multiple time points after stroke. The BI, which is a widely used instrument for longitudinal follow-up post-stroke, was used as reference to determine the effect of time on the sensitivity of the mRS in differentiating functional recovery. METHODS: Ninety-two patients with first stroke and hemispheric brain lesion were evaluated using the BI and mRS at 10 days, 3 and 6 months. The Kruskal-Wallis test was applied to examine median differences in BI among the mRS levels at 10 days, 3 and 6 months with Dunn's correction for multigroup comparison. The Mann and Whitney test was used to compare median differences in BI scores between two aggregations of mRS grades (mRS=0-2, mRS=3-5) at the same time periods after stroke. RESULTS: BI score distribution amongst mRS grades overlapped at 10 days, differentiating only between extreme grades (no disability vs severe disability). At 3 months, independent patients with slight disability could be distinguished from dependent patients with marked disability. At 6 months, grade 2 and 3 overlapped no more, differentiating independence (class 0-2) from dependence (class 3-5). The largest transition to an independent functional status occurred from grade 4, at 3 months. CONCLUSION: Maximum sensitivity of mRS in differentiating functional recovery is reached at six months post-stroke.

The efficacy and tolerability of a sunitinib 3-week administration schedule in metastatic renal cell carcinoma patients: report of three cases.

Sunitinib, an orally multitargeted tyrosine kinase inhibitor and standard first-line treatment for metastatic renal cell carcinoma, is usually administered on a 6-week schedule. Toxicities reported with this drug are usually of moderate grade, which results in good treatment tolerability and patients' compliance. However, in some cases high-grade or prolonged toxicities require temporary treatment interruption or dose adjustment, possibly resulting in reduced treatment efficacy. We describe three cases of metastatic renal cell carcinoma patients (a 53-year-old male, a 70-year-old woman, and a 65-year-old woman) who received a shortened 3-week sunitinib administration schedule, 2 weeks daily administration followed by 1 week of rest (2/1) due to toxicities developed on the classic 6-week schedule, which would have required a temporary treatment interruption or a dose reduction. Treatment was generally well tolerated with manageable toxicities. A 3-week administration schedule of sunitinib may represent a valid alternative for managing toxicity while maintaining the planned dose intensity over a 6-weeks period of time. Sunitinib may thus be administered using a flexible dosing schedule to meet individual patient needs, achieving better tolerability and maintaining significant response to treatment.

A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer.

Germline variants in the 3' untranslated region (3'UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3'UTR of the KRAS oncogene, referred to as the KRAS variant, is associated with both cancer risk and altered tumor biology. Here, we test the hypothesis that the KRAS variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS variant-positive EOC patients. As this variant seems to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival. EOC patients with complete clinical data were genotyped for the KRAS variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125) and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were used to confirm altered sensitivity to chemotherapy associated with the KRAS variant. Finally, the KRAS variant was directly targeted through small-interfering RNA/miRNA oligonucleotides in cell lines and survival was measured. Postmenopausal EOC patients with the KRAS variant were significantly more likely to die of ovarian cancer by multivariate analysis (hazard ratio=1.67, 95% confidence interval: 1.09-2.57, P=0.019, n=279). Perhaps explaining this finding, EOC patients with the KRAS variant were significantly more likely to be platinum resistant (odds ratio=3.18, confidence interval: 1.31-7.72, P=0.0106, n=291). In addition, direct targeting of the KRAS variant led to a significant reduction in EOC cell growth and survival in vitro. These findings confirm the importance of the KRAS variant in EOC, and indicate that the KRAS variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this study supports the hypothesis that these tumors have continued dependence on such 3'UTR lesions, and that direct targeting may be a viable future treatment approach.

Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients.

BACKGROUND: To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis. METHODS: Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4-EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated. RESULTS: Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort. CONCLUSION: We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.

Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient.

BACKGROUND: The activity of sunitinib, a multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activities, has been explored in several solid malignancies such as breast, lung, prostate and pancreatic cancer. Currently it is approved for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Non-small cell lung cancer usually presents at an advanced or metastatic stage at diagnosis. Treatment options are limited for this disease, therefore symptom palliation and patient's quality of life are primary objectives of therapy. CASE REPORT: We describe the case of a patient (male, 67 years old) with heavily pre-treated metastatic non-small cell lung carcinoma who received sunitinib according to the following 3-week schedule: 50 mg daily for 2 weeks followed by a 1-week rest. The patient completed six months of therapy achieving a major disease response without high-grade toxicities. CONCLUSION: In this case, sunitinib shows promising single-agent activity in pretreated non-small cell lung cancer, with a good toxicity profile and flexible administration schedule.

Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas.

This study identifies the genetic fingerprint of poorly differentiated endometrioid endometrial carcinomas (G3-EEC) and analyses the potential utility of trefoil factor 3 (TFF3) as novel serum marker in G3-EEC. Affymetrix microarrays were used to identify the gene expression patterns of 19 snap-frozen G3-EEC and 15 normal endometrium (NE) biopsies. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to validate TFF3 expression. Finally, TFF3 serum levels were determined by ELISA in 25 G3-EEC patients, 42 healthy controls, and in 13 endometrial hyperplasia patients. Hierarchical cluster analysis showed TFF3 as the top differentially expressed gene between 363 upregulated genes in G3-EEC, when compared with NE. Trefoil factor 3 gene expression levels analysed by qRT-PCR significantly correlated with Affymetrix results (P<0.001; rs=0.85). By immunohistochemistry, TFF3 protein was significatively more expressed in EEC compared with NE (P<0.01), with cytoplasmatic positivity in 79% G3-EEC and 18% NE. Patients harbouring G3-EECs had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients (P<0.001) or patients harbouring endometrial hyperplasia (P=0.012). In conclusion, TFF3 is highly expressed at gene and protein level in G3-EEC. Further investigations on a wider set of samples are warranted to validate TFF3 as a novel serum marker for early detection and/or monitoring of G3-EEC patients.

Claudin-7 expression in human epithelial ovarian cancer.

Claudin-7 (CLDN-7) is a tight junction protein recently found highly differentially expressed in ovarian carcinoma. To evaluate its potential as a novel biomarker, in this study, we quantified and compared claudin-7 expression at messenger RNA and protein level in 110 patients harboring various histologic types of epithelial ovarian carcinomas (EOC). CLDN-7 transcript was found significantly overexpressed in both primary and metastatic EOCs compared to normal human ovarian surface epithelium cell lines (fold change = 111.4, P < 0.001) by reverse transcription-polymerase chain reaction. At the protein level, CLDN-7 expression was found significantly higher in tumors of primary and metastatic origin when compared to normal ovaries (P < 0.001), regardless of the histologic type, the grade of differentiation, and the pathologic stage of the disease (P = 0.12). Moreover, a strong immunoreactivity for CLDN-7 was detected in EOC cells present in ascites fluids, whereas ascites-derived inflammatory cells, histiocytes, and reactive mesothelial cells were negative. Finally, immunohistochemical expression of CLDN-7 was observed in several human normal epithelial control tissues analyzed. CLDN-7 is significantly overexpressed in all main histologic types of EOC and in single neoplastic cells disseminated in peritoneal cavity and pleural effusions, suggesting its potential role as novel diagnostic marker in ovarian cancer. Despite widespread expression of CLDN-7 in several human normal tissues, the high density of CLDN-7 molecules, their membranous localization on EOC cells, and their lack of expression on the celomic epithelium in the peritoneal cavity suggest that this target could be potentially suitable for antibody-mediated localized therapies of ovarian adenocarcinoma.

HER-2/neu overexpression and amplification in uterine serous papillary carcinoma: comparative analysis of immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization.

Uterine serous papillary carcinoma (USPC) is a rare and highly malignant form of endometrial cancer (EC) characterized by early metastasis, chemoresistance, and high mortality rate. Little is known about USPC tumorigenesis even if recently a HER-2/neu role has been suggested in its development and progression. The aim of the present study was to evaluate HER-2 expression by immunohistochemistry (IHC) in 12 USPC formalin-fixed, paraffin-embedded (FFPE) samples. Moreover, we looked at the correlation between HER-2 protein expression and HER-2/neu gene amplification by fluorescence in situ hybridization (FISH), other than HER-2/neu messenger RNA expression by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Finally, these results have been compared with commonly evaluated clinical features in EC patients, in order to define the potential prognostic value of HER-2/neu overexpression in USPCs. A high expression of HER-2 protein by IHC was noted in 2 of 12 patients (16.6%), and the same cases showed specific HER-2/neu gene amplification by FISH. All the samples investigated displayed a perfect concordance between IHC and FISH data. Five (41.6%) of 12 tumors demonstrated polysomy of chromosome 17 and, focusing on the 2 USPCs that showed HER-2/neu overexpression, one of them (50%) was polysomic for chromosome 17. All the other USPC cases (58.4%) showed to be disomic for chromosome 17. Quantitative RT real-time PCR performed on complementary DNA obtained from all FFPE USPC samples showed a complete correlation with FISH and IHC data. Moreover, HER-2/neu overexpression was associated with a poorer overall survival and a very low relapse-free survival time, thus being considered a candidate marker of worse overall prognosis in USPC. The use of trastuzumab (Herceptin), a monoclonal antibody directed against HER-2/neu, for the therapy of patients with HER-2/neu-positive USPCs should be further investigated in clinical trials.

Mammaglobin B expression in human endometrial cancer.

Mammaglobin B (MGB-2) is an uteroglobin gene family member recently found highly differentially expressed in ovarian cancer by gene expression profiling. To evaluate its potential as a novel endometrial cancer biomarker, in this study we quantified and compared MGB-2 expression at messenger RNA and protein levels in endometrial tumors (endometrioid endometrial cancer [EEC]) with different grades of differentiation. MGB-2 expression was evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) in fresh frozen biopsies and paraffin-embedded tissues derived from a total of 70 patients including 50 primary EEC and 20 normal endometria (NECs). High levels of MGB-2 gene expression were detected in 10 of 11 EEC G1 cases (91%), 16 of 17 EEC G2 cases (94%), and 6 of 22 EEC G3 cases (27%) by real-time PCR. In contrast, normal endometrial cells expressed low to negligible levels of MGB-2 by real-time PCR (P = 0.002 EEC vs NEC). Well- and moderately differentiated EECs overexpressed MGB-2 gene at significant higher levels when compared to NECs (P < 0.01). Pairwise differences between both G2 and G1 vs G3 cases for MGB-2 relative gene expression values were also statistically significant (G2 vs G3 P < 0.001, G1 vs G3 P = 0.016). MGB-2 protein expression was detected in 31 (86%) of 36 EEC and 0 of 5 atrophic NEC controls, while seven of eight (88%) of the proliferative/secretory/hyperplastic NECs focally expressed MGB-2 by IHC. MGB-2 is highly expressed in EEC, particularly in well- and moderately differentiated tumors, and may represent a novel molecular marker for EEC.

Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients.

Human papillomaviruses (HPVs), particularly HPV-16/18, are linked to cervical cancer development. Full-length, recombinant HPV-16/18 E7 oncoproteins were used in a new streptavidin-biotin capture ELISA method to investigate anti-HPV E7 antibody prevalence in serum. Sera from 99 healthy women, 70 cervical cancer patients, and 30 patients with cervical pre-invasive neoplasia were analyzed. Anti-HPV-16/18 E7 positivity was found in 53% of cervical cancer patients, in 40% with cervical pre-invasive neoplasia, and in 8% of healthy women. Serum samples from 12 cervical cancer patients were obtained at different time intervals during the treatment. Eleven out of 12 showed a correspondence between HPV-E7 antibody levels (decreasing versus increasing) and the type of response (clinically complete or partial response versus progression or stable disease) at each serological evaluation. Five patients with recurrent HPV-16/18-positive cervical carcinoma were analyzed before and after vaccination with HPV-16/18 E7-pulsed autologous dendritic cells; anti-HPV-16/18 E7 positivity was found in 3 out of 5 women. In conclusion, this assay could potentially be used as an adjunctive tool to monitor the type of response to treatment and possibly to detect antibody induction in cervical cancer patients after vaccination, as a potential marker to evaluate its efficacy.

[Idiopathic sudden hearing loss: role of the posterior communicating cerebral arteries of the Willis' circle]. / Ipoacusia improvvisa idiopatica: ruolo delle arterie cerebrali comunicanti posteriori del circolo di Willis.

Sudden hearing loss (SHL) is a neurosensorial hearing loss of variable entity with an onset of less than three days. In most cases (85-90%) it is of unknown etiology (idiopathic sudden hearing loss--ISHL). The most accredited hypotheses for origin are: viral, immunitary and vascular. ISHL accounts for approximately 1% of all neurosensorial hearing loss; onset is most frequent in winter, i.e. January and February, and it most frequently affects women, particularly at 15 and between 40-50 years of age. In order to evaluate the role of vascular condition on the onset of ISHL, we focused our attention on the circle of Willis. The results confirm that, in the absence of cerebro-vascular pathology, posterior communicating arteries (PCAs) that cannot be activated--evaluated by transcranial Doppler (TCD)--are associated with ISHL. Moreover, hemodynamic alterations detected in the basilar artery in ISHL patients are correlated with the final prognosis for hearing. These observations highlight the importance of TCD in testing subjects at risk for idiopathic SHL and show that PCAs are essential in maintaining normal cochlear function.

Non-functioning posterior communicating arteries of circle of Willis in idiopathic sudden hearing loss.

Most cases of sudden hearing loss have no identifiable cause. A link between compensatory blood flow through the circle of Willis and recovery from sudden hearing loss has, however, been suggested. We assessed 22 patients with sudden hearing loss who had no cerebrovascular disease, and 41 controls matched for age and sex. We took ultrasonographic doppler flow measurements of the extracranial carotid and vertebrobasilar systems and independent audiological measurements. 12 patients with sudden hearing loss, compared with four controls had bilateral non-functioning posterior communicating arteries (p=0.00019). Our findings suggest a strong association between a non-functioning posterior communicating artery of the circle of Willis and sudden hearing loss.

[A case of cerebral angioma: non-invasive instrumental diagnosis]. / Un caso di angioma cerebrale: diagnostica strumentale non invasiva.

A case of cerebral angioma: non-invasive assessments. A 65-year-old woman, suffering from epileptic seizures since the age of 6, was examined. Transcranial Doppler (TCD) ultrasounds, SEPs and EEG brain mapping by means of median nerve stimulation, were performed, followed by a NMR of the brain, which revealed an arteriovenous malformation in the left hemisphere (frontal and parietal lobe). By comparing the results of the neurophysiological tests, the diagnostic value of TCD, confirmed by the neuroradiologic findings, was established. EEG and SEPs were also abnormal, but their actual effectiveness in clinical studies is discussed. We conclude that these electrophysiological examinations do not allow a reliable diagnosis as with TCD.