Validation of modular endoscopic medial maxillectomies for inverted papilloma of the maxillary sinus.

BACKGROUND: Treatment of inverted papilloma of the maxillary sinus (IPMS) has a lower success rate compared to other IPs. As such, its correct management generally needs trans-nasal endoscopic medial maxillectomy (EMMs) for adequate resection. The aim of this manuscript is to describe outcomes and major prognostic factors of a cohort of patients with IPMS who were treated with EMM. METHODOLOGY: In this multicentric study, patients affected with IPMS and treated with EMMs were included. The site of origin of the IPMS were studied as well as the type of EMM performed. The histological features (IP vs dysplasia), type of mucosal resection (total vs. pedicle oriented), and post-operative complications were analyzed. RESULTS: 310 patients were included (212 primary and 98 recurrent cases). After a mean follow-up of 45.4 months, 15 patients experienced recurrence (4.8%) due to the application of EMMs tailored to the surgical insertion point. Dysplasia was significantly associated with a higher risk of recurrence. The rates of early and late complications were 11.6% and 11.9%, respectively. CONCLUSIONS: IPMS resection via tailored EMM is associated with excellent disease control, thus excluding the systematic use of extended EMMs, which can however be justified in case of dysplastic IPMS given its significant impact on recurrence.

A combined molecular dynamics simulation and DFT study on mercapto-benzamide inhibitors for the HIV NCp7 protein.

Molecular dynamics and quantum simulations are performed to elucidate some aspects of the action mechanism of mercapto-benzamides, a proposed class of antivirals against HIV-1. These molecules act as prodrugs that, after modifications in the biological environment, are able to denature the HIV nucleocapsid protein 7, a metal binder protein, with two zinc finger motifs, vital for RNA maturation and viral replication. Despite their attractive features, these molecules and their biological target are not well understood. Simulations were performed to support a proposed action mechanism, based on the activation of mercapto-benzamides by acetylation, targeting a relatively rare protein hydrolyzed state, followed by trans-molecular acetylation from the molecule to the protein and finally the direct interaction of the molecular sulphur atom of mercapto-benzamides with the zinc atom coordinated by the protein. Our simulation results are in agreement with the NMR data about the zinc finger binding protein equilibrium configurations.

The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients.

PURPOSE: Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene, located on chromosome 9p21 has been demonstrated to be the commonest cause of familial amyotrophic lateral sclerosis (ALS) and to account for 5 to 10 % of apparently sporadic ALS. Relatively little is known about the brain metabolism profile of patients carrying the expansion. Our aim was to identify the [(18)F]FDG PET profile in ALS patients with the C9ORF72 expansion (C9ORF72-ALS). METHODS: Fifteen C9ORF72-ALS patients were compared with 12 patients with ALS and comorbid frontotemporal dementia (FTD) without the C9ORF72 expansion (ALS-FTD) and 30 cognitively normal patients with ALS without mutations of ALS-related genes (sALS). The three groups were then cross-matched to 40 neurologically normal controls. All patients underwent FDG PET within 4 months of diagnosis. RESULTS: The C9ORF72-ALS patients compared with the sALS patients showed significant hypometabolism in the anterior and posterior cingulate cortex, insula, caudate and thalamus, the left frontal and superior temporal cortex, and hypermetabolism in the midbrain, bilateral occipital cortex, globus pallidus and left inferior temporal cortex. The ALS-FTD patients compared with the sALS patients showed more limited hypometabolic areas, including the orbitofrontal, prefrontal, anterior cingulate and insular cortex, and hypermetabolic areas, including the bilateral occipital cortex, the left precentral and postcentral cortex and superior temporal gyrus. The C9ORF72-ALS patients compared with the ALS-FTD patients showed hypometabolism in the left temporal cortex. CONCLUSION: ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more widespread central nervous system involvement than ALS patients without genetic mutations, with or without comorbid FTD, consistent with their more severe clinical picture.

Formaldehyde and methylene glycol equivalence: critical assessment of chemical and toxicological aspects.

Due largely to the controversy concerning the potential human health effects from exposure to formaldehyde gas in conjunction with the misunderstanding of the well-established equilibrium relationship with its hydrated reaction product, methylene glycol, the concept of chemical equivalence between these two distinctly different chemicals has been adopted by regulatory authorities. Chemical equivalence implies not only that any concentration of methylene glycol under some condition of use would be nearly or completely converted into formaldehyde gas, but also that these two substances would be toxicologically equivalent as well. A relatively simple worst case experiment using 37% formalin (i.e., concentrated methylene glycol) dispels the concept of chemical equivalence and a review of relevant literature demonstrates that methylene glycol has no inherent toxicity apart from whatever concentration of formaldehyde that might be present in equilibrium with such solutions.

DGAT1 mutation in two sisters with failure to thrive: a case report. / Mutación DGAT1 en dos hermanas con falla de medro: reporte de caso.

Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that have been described in recent years. Within the CODEs, the mutation in the diacylglycerol O-acyltransferase 1 (DGAT1) gene is a rare enzyme disorder associated with severe, early-onset chronic diarrhea. Our objective is to describe the case of 2 sisters who consulted for chronic diarrhea, growth retardation, vomiting, and hypoalbuminemia in early childhood. A compound heterozygous DGAT1 mutation was found in both patients. This mutation was previously described in the Asian population; however, these are the first 2 patients to show this mutation in the Latin American population. These 2 cases may expand our knowledge about congenital diarrhea in general and the clinical characteristics of patients with DGAT1 mutations in particular.

Las diarreas y enteropatías congénitas (CODE por su sigla en inglés) son un grupo de trastornos monogénicos que se han descrito en los últimos años. Dentro de las CODE, la mutación del gen de la diacilglicerol o-aciltransferasa 1 (DGAT1) es un trastorno enzimático poco común asociado con diarrea crónica grave de aparición temprana. El objetivo es presentar a dos hermanas que consultaron por diarrea crónica, retraso en el crecimiento, vómitos e hipoalbuminemia en la primera infancia. En ambas pacientes se encontró un compuesto heterocigota de la mutación del DGAT1. Esta mutación se describió previamente en la población asiática; sin embargo, estas son las dos primeras pacientes en tener esta mutación en la población latinoamericana. Estos dos casos pueden ampliar nuestro conocimiento sobre las diarreas congénitas en general y las características clínicas de los pacientes con mutaciones en DGAT1 en particular.

Intraoperative anaphylaxis: a case report of allergy to ranitidine.

We report the case of a 18-year old male who developed intraoperative anaphylaxis. The presence of specific IgE to ranitidine was documented This case confirms the possibility of anaphylaxis at first exposure.

Interobserver agreement in breast radiological density attribution according to BI-RADS quantitative classification.

PURPOSE: The authors sought to assess interobserver agreement in classifying mammography density according to quantitative Breast Imaging Reporting and Data System (BI-RADS) criteria. MATERIALS AND METHODS: Six expert mammography readers were tested on a set of 100 mammograms. Interobserver agreement was determined according to the kappa statistic, adjusting for chance agreement, on a four-category (D1 vs. D2 vs. D3 vs. D4) or two-category (D1-2 vs. D3-4) basis. Agreement with a panel of 12 readers who had been tested on the same set in a previous study was also assessed. RESULTS: The six readers showed good agreement when compared in pairs [agreement on a four-category basis was substantial (kappa=0.60-0.80) for 13 pairs and almost perfect (kappa>0.80) for two pairs); agreement on a two-category basis was substantial for 12 pairs and almost perfect for three pairs) or compared with the panel (on a four-category basis, agreement was substantial for five of six readers and almost perfect for one; on a two-category basis, agreement was substantial for all readers). CONCLUSIONS: In agreement with previous studies, visual classification of mammography density according to BI-RADS quantitative criteria was highly reproducible among readers; nevertheless, attribution to the "dense breast" (BI-RADS D3-4) category, which might be adopted as a determinant of different screening protocols (such as adjunct ultrasonography or yearly interval) varied among readers (range 6-15%). Controlled studies should be performed comparing visual with computer-density category attribution, the latter possibly being a better alternative due to its absolute reproducibility.

Efforts for the Correct Comprehension of Deceitful and Ironic Communicative Intentions in Schizophrenia: A Functional Magnetic Resonance Imaging Study on the Role of the Left Middle Temporal Gyrus.

Deficits in social cognition and more specifically in communication have an important impact on the real-life functioning of people with schizophrenia (SZ). In particular, patients have severe problems in communicative-pragmatics, for example, in correctly inferring the speaker's communicative intention in everyday conversational interactions. This limit is associated with morphological and functional alteration of the left middle temporal gyrus (L-MTG), a cerebral area involved in various communicative processes, in particular in the distinction of ironic communicative intention from sincere and deceitful ones. We performed an fMRI study on 20 patients with SZ and 20 matched healthy controls (HCs) while performing a pragmatic task testing the comprehension of sincere, deceitful, and ironic communicative intentions. We considered the L-MTG as the region of interest. SZ patients showed difficulties in the correct comprehension of all types of communicative intentions and, when correctly answering to the task, they exhibited a higher activation of the L-MTG, as compared to HC, under all experimental conditions. This greater involvement of the L-MTG in the group of patients could depend on different factors, such as the increasing inferential effort required in correctly understanding the speaker's communicative intentions, and the higher integrative semantic processes involved in sentence processing. Future studies with a larger sample size and functional connectivity analysis are needed to study deeper the specific role of the L-MTG in pragmatic processes in SZ, also in relation to other brain areas.

Type and trends in outcomes research in breast cancer between 2000 and 2007.

BACKGROUND: Interest in outcomes research (OR) derives from the need to know the value and the effectiveness of health interventions, especially for oncology. We focused our research on OR in breast cancer, providing an overview of the trend of publications. PATIENTS AND METHODS: We carried out a Medline search to retrieve all articles in English published from 2000 through 2007. The abstracts were reviewed and classified according to the research topics and the primary design of the trial. RESULTS: We selected 405 articles: their number remained constant until 2003, rose during 2004-2005 and decreased during the last 2 years. The most common topic was surgery (n = 234), alone or in association with other interventions. The category more investigated was the process. Clinical outcomes, and among them disease-free survival, were more frequent than other outcomes. The median value of 2007 Impact Factor of the journals publishing the selected references was 2.466 (range 0.272-25.547) and the median value of Citation Index was 8 (range 0-143). CONCLUSIONS: Our research showed a decreasing interest in OR during the more recent years. We are hopeful that it will regenerate interest, particularly by the light of the funds allocated to the comparative effectiveness research in the United States.

Identification of a new HLA-B*08 allele in a family of Iraqi origin.

The novel allele HLA-B*08:62 differs from HLA-B* 08:01:01 by a nonsynonymous nucleotide substitution at position 24 of exon 2 (codon 9 changes from GAC to CAC).

Analysis of proportional incidence and review of interval cancer cases observed within the mammography screening programme in Trento province, Italy.

PURPOSE: The aim of this study was to assess the performance of the mammography screening programme in Trento Province, Italy, by analysing the interval cancers (IC) observed from 2001 to 2008. MATERIAL AND METHODS: IC were identified by linking screening archives with local cancer registry and pathology archives as well as with hospital discharge records. Proportional incidence was determined according to breast cancers expected in the absence of screening, estimated on the basis of patients/year at risk and age-specific incidence. The review of screening mammograms preceding ICs was performed by an external (three radiologists) and an internal (five radiologists) panel and aimed at assessing the proportion of IC reviewed as screening errors. Results were compared with European Community (EC) recommended standards. RESULTS: IC proportional incidence was 15.90% for the first year (EC standard <30%) and 25.77% for the second year (EC standard <50%) of the interval. At external review, 18.4% of cases were reviewed as screening errors (identified by at least two of three reviewers), whereas at internal review (identified by at least three of five reviewers) it was 17.4% (EC standard <20%). No significant difference was observed between external and internal review (mean recall rate 8.3% vs. 9.0%; mean identification rate 19.7% vs 19.6%). CONCLUSIONS: The study confirms good performance of the mammography screening programme in Trento Province, Italy. Comparable results of external and internal reviews suggest that the latter, no doubt easier to be implemented, might be adopted as a routine procedure to assess this early efficacy indicator.

High preoperative serum vascular endothelial growth factor levels predict poor clinical outcome after curative resection of gastric cancer.

BACKGROUND: Tumour vascular endothelial growth factor (VEGF) and tumour urokinase-type plasminogen activator (uPA) are prognostic factors in gastric cancer but surgical specimens are required for testing. The prognostic value of preoperative serum VEGF (s-VEGF) and serum uPA (s-uPA) levels was evaluated in patients undergoing potentially curative (R0) gastric cancer resection. METHODS: Concentrations of s-VEGF and s-uPA were measured 97 patients with gastric cancer and 20 controls. Angiogenesis was measured in vitro based on human endothelial cell tube formation. RESULTS: Levels of s-VEGF were higher in patients with gastric cancer than controls (median 288 versus 189 pg/ml respectively; P = 0.002). They were associated with pathological tumour node metastasis (pTNM) stage, pT, pN, lymph node ratio and perineural invasion, and correlated with platelet counts. In multivariable analysis, s-VEGF over 320 pg/ml was the only preoperative predictor of both recurrence and disease-specific survival. Serum from patients with raised s-VEGF levels enhanced angiogenesis in vitro significantly more than serum from those with a s-VEGF level of 320 pg/ml or less. CONCLUSION: High preoperative s-VEGF level is an independent prognostic factor for recurrence and survival after R0 resection of gastric cancer. This may provide a useful guide to decision making regarding neoadjuvant and adjuvant therapies.

Humoral immunity to respiratory syncytial virus in young and elderly adults.

Respiratory syncytial virus (RSV) has been demonstrated to cause substantial disease in elderly and immunocompromised subjects. The relationship of serum antibody to RSV infection and the risk of infection in elderly subjects is controversial, thus we evaluated the presence of neutralizing antibodies to RSV in healthy people of different age groups and the correlation with viral protection. Baseline blood samples from 197 subjects aged 20-80 years were analysed for the presence of anti-RSV antibodies either by indirect immunofluorescence and microneutralization test. The percentage of people who had neutralizing antibodies to RSV was significantly higher (P=0.001) in the youngest group (92.51%) compared to the frail group (36.21%). The RSV antibody level tends to wane in some older people; this factor could determine proneness to RSV re-infections in the elderly who are at a greater risk of developing severe respiratory disease.

Periprosthetic hip and knee infections: comparison of etiology, perioperative management and costs.

OBJECTIVE: We compared two series of patients treated at our Hospital for periprosthetic hip and knee infections (PHI; PKI), in order to evaluate etiology, perioperative management (duration of spacer, antibiotic therapy, quality of life during the treatment), length of hospital stay, and costs. PATIENTS AND METHODS: We included in the study 32 patients with PHI and 30 patients with PKI. The average age of the patients was 74.8 in PHI and 71.2 in PKI. Treatment consisted of a two-stage revision associated with antibiotic therapy. All patients were followed up for at least two years after surgery. We analyzed the causative microorganism responsible for the infection, duration of the spacer and antibiotic therapy, quality of life during this time, length of hospital stay, and total hospital cost of treatment. RESULTS: The gram-negative microorganisms were more common in PHI, without any statistically significant difference compared to PKI. Duration of the spacer for PHI was 7.4 months and 5.5 months for PKI (p=0.005). Length of antibiotic therapy was 6.2 months for PHI and 4.1 months for PKI (p<0.001). Most patients in the two series had an acceptable quality of life during treatment. The mean length of hospitalization was 54 days in PHI and 26 days in PKI (p<0.001). The cost averaged 38,300 euros for PHI and 22,100 euros for PKI (p<0.001). CONCLUSIONS: Our study showed statistically significant differences between periprosthetic hip and knee infections as regards etiology, duration of treatment and global costs. Periprosthetic hip infections are caused by more virulent microorganisms that are harder to eradicate, require a longer length of treatment and have a greater economic impact on the healthcare system.

Residual haptic sensation following stroke using ipsilateral stimulation.

In 1987, Weiskrantz and Zhang described a stroke patient with severe somatosensory loss who, nevertheless, demonstrated impressive residual sensory performance when required to touch the affected limb with her ipsilesional hand (self touch; ST). The current study set out to ascertain the prevalence and characteristics of self-touch enhancement (STE) in patients with unilateral stroke and hemihypaesthesia. Thirty-nine stroke patients who were referred with hemihypaesthesia fulfilled the criteria. STE was defined where a patient showed a statistically significant increase (p<0.05) in performance for (i) detection, (ii) localisation and/or (iii) perceived intensity during touch with their ipsilesional hand, compared with standard experimenter elicited sensory performance. Group comparisons between the conventional touch versus ST conditions revealed significant differences for detection (p<0.01), intensity estimation (p<0.01) and localisation (p<0.001) using ST. Twenty-two of the 39 patients (56.4%) showed STE on at least one assessment mode. In detection, 16 (41%) patients showed STE; for localisation, 12 patients (31%) showed STE and for intensity, 17 patients (44%) showed STE. Out of the 22 patients with STE, 17 had right hemisphere lesions. In summary, more than half of the stroke patients showed reliable and significant improvements in somatosensory performance when using their unaffected hand as the source of tactile stimulation. This striking phenomenon suggests that the threshold for the impaired hand is affected by active involvement of the contralateral (ipsilesional) limb when delivering the stimulus contact. Possible mechanisms to explain these findings are discussed.

Mutación DGAT1 en dos hermanas con falla de medro: reporte de caso / DGAT1 mutation in two sisters with failure to thrive: a case report

Las diarreas y enteropatías congénitas (CODE por su sigla en inglés) son un grupo de trastornos monogénicos que se han descrito en los últimos años. Dentro de las CODE, la mutación del gen de la diacilglicerol o-aciltransferasa 1 (DGAT1) es un trastorno enzimático poco común asociado con diarrea crónica grave de aparición temprana. El objetivo es presentar a dos hermanas que consultaron por diarrea crónica, retraso en el crecimiento, vómitos e hipoalbuminemia en la primera infancia. En ambas pacientes se encontró un compuesto heterocigota de la mutación del DGAT1. Esta mutación se describió previamente en la población asiática; sin embargo, estas son las dos primeras pacientes en tener esta mutación en la población latinoamericana. Estos dos casos pueden ampliar nuestro conocimiento sobre las diarreas congénitas en general y las características clínicas de los pacientes con mutaciones en DGAT1 en particular.

Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that have been described in recent years. Within the CODEs, the mutation in the diacylglycerol O-acyltransferase 1 (DGAT1) gene is a rare enzyme disorder associated with severe, early-onset chronic diarrhea. Our objective is to describe the case of 2 sisters who consulted for chronic diarrhea, growth retardation, vomiting, and hypoalbuminemia in early childhood. A compound heterozygous DGAT1 mutation was found in both patients. This mutation was previously described in the Asian population; however, these are the first 2 patients to show this mutation in the Latin American population. These 2 cases may expand our knowledge about congenital diarrhea in general and the clinical characteristics of patients with DGAT1 mutations in particular.

Intima-media thickness of common carotid as cardiovascular risk factor in rheumatoid arthritis and metabolic disorders.

OBJECTIVES: To study the intima-media thickness (IMT) of the common carotid artery and the lipid profile in patients with rheumatoid arthritis (RA), type 1 diabetes mellitus T1DM), and obesity (Ob), against a control group of normal subjects (NS), in order to determine the relationship between cardiovascular risks and pro-atherosclerosis conditions in various inflammatory and metabolic disorders. MATERIALS AND METHODS: 147 subjects, with written consent, were divided into the following categories: 38 patients with RA (6m/32f; average age 51.7+/-4.4 years, range 42-71); 42 patients with T1DM (20m/22f; average age 52.1+/-6.2 years, range 45-65); 37 patients with obesity (20m/17f; average age 53.8+/-5.3 years, range 46-70); 30 normal subjects, age and sex matched, that make up the control group (14m/16f; average age 52.5+/-4.6, range 40-62). The IMT and the plaques were measured (values expressed in mm) according to the guidelines of the GIUV (Gruppo Italiano Ultrasonologia Vascolare, Italian Group of Vascular Ultrasonology). RESULTS: Our research has revealed the presence of a thickening of the intima-media complex in patients suffering from RA, highlighting, at the same time, that the atherosclerotic risk factor in these patients manifested regardless of the activity of the disease or the serum level. CONCLUSIONS: The presence of an inflammatory systemic chronic disease such as rheumatoid arthritis, seems to constitute a significant and independent atherosclerosis risk in itself, which apparently does not correlate with the lipid profile.

[The d.p.r. 37/97 and the thermal comfort of the surgeons according to the new version of UNI EN ISO 7730]. / Il d.p.r. 37/97 e il benessere termico dello staff operatorio alla luce della nuova versione dello standard UNI-EN-ISO 7730.

The Italian law, through a specific government decree (d.p.r. 37/97), recommends the minimal technological, structural and organising requirements that surgery rooms of public hospitals must assure. Nevertheless, thermal comfort is usually evaluated by the indices PMV and PPD (Fanger's indices). Microclimatic data, acquired inside 80 surgery rooms over 20 public hospitals located in South of Italy, have been reviewed taking into account the new version of the international standard UNI EN ISO 7730. This version enables to classify the workers in three categories, A, B and C each one related to a different value of the acceptable number of dissatisfied people PPD. Considering the particular task which surgeons and nurses are involved in, a percentage of dissatisfied < 6% appears more realistic and conservative respect to the 10% prescribed in the old version of the standard. So the calculations show that, in this case, less than 17% of the staff would considered the thermal conditions as comfortable. Furthermore, the range of the microclimatic parameters, as established by the low, is not sufficient to assure thermal comfort using the PMV or PPD.

[Study on prevalence of upper and lower airways disorders in woodworkers, using data from medical surveillance reports and exposure registers]. / Indagine sulla presenza di alterazioni delle vie respiratorie superiori ed inferiori in esposti a polveri di legno, utilizzando i dati della sorveglianza sanitaria e dei registri di esposizione.

OBJECTIVES: To evaluate correlations between exposure to wood dust, upper airways symptoms and lung function. METHODS: We have analysed medical surveillance reports of 197 woodworkers with a median wood dust TWA exposure of 2.1 mg/m3. Every worker was examined by an otorhinolaryngologist and had a spirometric test. The results have been analysed with logistic regression to correlate prevalence of symptoms and spirometric data with occupational exposure to wood dust, length of service, regular use of respiratory protection and smoking habits. RESULTS: Epistaxis (prevalence: 10.1%) correlates with no smoking habits (OR = 6.4; p = 0.01); subacute or chronic rhinitis (prevalence: 41.6%) correlates with exposure to wood dust (O = 1.37; p = 0.01) and no use of respirstory protection (OR = 1.68; p = 0.09); subacute or chronic pharyngitis (prevalence: 17.2%) has a weak but significant correlation with length of service (OR = 1.03; p = 0.05); decrease in FEF25-75 (prevalence: 19.8%) correlates with no use of respiratory protection (OR = 2.56; p = 0.02) and exposure to wood dust (OR = 1.29; p = 0.09); pathologic decrease of VC (prevalence: 5.1%) correlates with exposure to wood dust (OR = 1.69; p = 0.05). CONCLUSIONS: this study seems to confirm that chronic irritation of upper and lower respiratory tract are caused by exposure to wood dust below the european 8 hours exposure legal limit of 5 mg/m3.