Covid-19 pandemic and clinical activity stop: oral health study in a group of children.

AIM: Public and private health services, which provide both preventive and health promotion interventions, were forced to suddenly stop their activities to limit the risk of infections during the pandemic emergency. Oral health administration, including that of children, was affected by these planned medical service closures, from both therapeutic and preventive perspectives. This study aims to analyse the consequences, at the oral cavity level, of failures to treat patients of childhood age, considering the impact of carious pathology on quality of life and incorrect eating and oral hygiene habits, which may occur in this age group. METHODS: This is a cross-sectional, single-center, observational study. One hundred patients from the Odontostomatological University Center (C.O.U.) of Perugia were randomly enrolled. CONCLUSION: Oral health status of the examined sample is satisfactory overall, considering the clinic's interruption of treatments with the resulting long period of no follow-up and the emotional and economic stress generated by the pandemic condition for both the young patients and their caregivers.

Biological effects of resin monomers on oral cell populations: descriptive analysis of literature.

AIM: Recently, the application of restorative materials containing metacrilate monomers in the conservative and paediatric dentistry has focused on the possible negative effects due to the use of these composites. In particular the release of monomers from reconstructions as a result of an insufficient polymerisation, can spread along the mucosal and dental tissues with potential immunological ed cytotoxic effects. Regarding to the importance of this issue, the aim of this study is to provide a descriptive review of the literature on potential local and systemic interactions of metacrylic and acrylic monomers with the immune system, both in vitro and in vivo. RESULTS: The most highly used monomers in composite materials applied in conservative dentistry include: 2-hydroessietil- methacrylate (HEMA), triethylene glycol-dimethacrylate (TEGDMA), bisphenol A glycidyl-methacrylate (BisGMA) and urethane- dimethacrylate (UDMA). Different investigations have been performed for better understanding of the potential side effects of metacrylic monomers on immune system cells. Different factors such as cell population, exposure time and parameters more strictly connected to these materials, such as molecular weight, chemical composition and mechanical characteristics, seem to be directly involved in these reactions.

Blockade of nociceptive sensory afferent activity of the rat knee joint by the bradykinin B2 receptor antagonist fasitibant.

OBJECTIVE: The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia. METHODS: Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test. RESULTS: BK (100 µM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 µM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 µg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug. CONCLUSIONS: Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.

Fasitibant prevents the bradykinin and interleukin 1ß synergism on prostaglandin E2 release and cyclooxygenase 2 expression in human fibroblast-like synoviocytes.

This study investigates the effect of the selective and potent B(2) receptor antagonist fasitibant (MEN16132) on the proinflammatory effect of bradykinin (BK) and its interaction with interleukin 1ß (IL-1ß) in human synoviocytes. PGE(2) content was detected in the surnatants and COX-2 and COX-1 gene and protein expression determined in the cells. Radioligand binding ([(3) H]BK) and BK-induced inositolphosphate experiments were performed. Incubation of synoviocytes with BK induced a sustained production of PGE(2) and transient COX-2 gene expression that were prevented by pretreatment with fasitibant (1 µM, 30 min preincubation). IL-1ß increased PGE(2) release and COX-2 expression more than BK alone. The combined treatment of cells with BK and IL-1ß induced an even increase of released PGE(2) and COX-2 gene and protein expression indicating a synergistic rather than an additive effect, not related to an increase of B(2) receptors density or its coupling. These potentiating effects of BK on PGE(2) production and increased COX-2 expression produced by IL-1ß were B(2)-receptor-mediated as fasitibant could prevent them. None of the treatments induced changes in the COX-1 expression. The synergistic PGE(2) production was abolished by the specific NF-kappaB inhibitor (BAY-117085), whereas specific inhibitors for the p38 (SB203580), JNK (SP600125), and ERK1/2 (PD98059) mitogen-activated protein kinases could prevent the prostanoid release. BK can potentiate the COX-2 gene expression and consequent prostanoid production induced by IL-1ß. The prevention of this synergism by fasitibant indicates BK B(2) receptor blockade as an alternative symptomatic therapy for osteoarthritis.

Anti-inflammatory synergy of MEN16132, a kinin B(2) receptor antagonist, and dexamethasone in carrageenan-induced knee joint arthritis in rats.

BACKGROUND AND PURPOSE: Bradykinin, through its B(2) receptor, is involved in inflammatory processes related to arthropathies. In carrageenan and lipopolysaccharide (LPS)-induced arthritis in rat, the anti-inflammatory activity of MEN16132, a potent and selective kinin B(2) receptor antagonist, was compared with that of steroidal and nonsteroidal anti-inflammatory drugs. The interaction between MEN16132 and dexamethasone was also investigated. EXPERIMENTAL APPROACH: Drugs, alone or in combination, were injected into the knee joint 30min before intra-articular administration of carrageenan or LPS, in pentobarbital anaesthetized rats. Effects on incapacitation, oedema, neutrophil recruitment and kallikrein system activation, in the knee joint, were assessed. KEY RESULTS: MEN16132 and dexamethasone (10-300µg per knee) dose-dependently reduced carrageenan-induced joint pain, oedema and neutrophil infiltration, reaching a maximal inhibition of about 50%. Dexketoprofen exerted a similar analgesic activity, whereas it did not affect the other inflammatory responses. MEN16132 showed a partial inhibition of LPS-induced joint pain, whereas dexamethasone produced a full analgesic effect. Combination of MEN16132 and dexamethasone showed a strong synergistic interaction in inhibiting both carrageenan and LPS-induced knee joint inflammation. Dexamethasone did not prevent the contact activation of prekallikrein by carrageenan and the subsequent release of kallikreins and bradykinin in the synovium. CONCLUSIONS AND IMPLICATIONS: Steroids and kinin B(2) receptor antagonists appear to relieve arthritic symptoms induced by carrageenan or LPS and act synergistically to inhibit joint inflammation. This could have interesting therapeutic implications, possibly opening the way for combination therapies in the control of inflammatory arthropathies.

Megakaryocytic features useful for the diagnosis of myeloproliferative disorders can be obtained by a novel unsupervised software analysis.

An unsupervised method for megakaryocyte detection and analysis is proposed, in order to validate supplementary tools which can be of help in supporting the pathologist in the classification of Philadelphia negative chronic myeloproliferative disorders with thrombocytosis. The experiment was conducted on high power magnification photomicrographs taken from hematoxylin-and-eosin 3 micrometer thick sections of formalin fixed, paraffin embedded bone marrow biopsies from patients with reactive thrombocytosis or chronic myeloproliferative disorders. Each megakaryocyte has been isolated in the photos through an image segmentation process, mainly based on mathematical morphology and wavelet analysis. A set of features (e.g. area, perimeter and fractal dimension of the cell and its nucleus, shape complexity via elliptic Fourier transform, and so on) is used to characterize the disorders and discriminate between essential thrombocythemia and idiopathic myelofibrosis. Features related to the general contour of the cell like cytoplasmic area and perimeter are good markers in distinguishing between normal or reactive and pathologic megakaryocytes while nuclear features and global circularity are helpful in the differential diagnosis between ET and prefibrotic IMF. The method proposed should be considered as a fast preprocessing tool for the diagnostic phase and its use can be extended to solve different object recognition problems.

Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas.

AIMS: The aim of this work is the study of the prognostic significance of the chromosomal aberrations described in a series of invasive ductal breast carcinomas. METHODS AND RESULTS: We analysed by comparative genomic hybridization a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas. Aberrations showed a frequency similar to previous studies using frozen tumours. Interestingly, we identified gains involving 6q16-q24 more frequently than in other series. We analysed the association among the chromosomal imbalances, 11 histopathological factors, relapse rate and overall survival of patients. Associations showed 16q losses as a potential marker of good prognosis, as they were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063; P=0.066). Within the good prognosis group of lymph node-negative patients, 17q and 20q gains identify a subgroup with increased relapse rate (P=0.039). CONCLUSIONS: Chromosomal imbalances, together with histopathological factors, may help to predict outcome in breast cancer patients.

[Primary low-grade non-Hodgkin's B lymphoma mimicking meningioma]. / Linfoma dural primario no Hodgkin B de bajo grado simulando un meningioma.

Primary dural lymphomas are rare. Usually they present themselves as diffuse lesions and are infrequently well-delimited. We present a 44 year old male, who was admitted into our Centre after a generalised seizure. Neuroimage studies (CT scan, MRI and angiography) were performed, demonstrating a right hemispheric well-delimited extra-axial mass, being diagnosed initially as meningioma. The patient underwent surgery with radical scission of the mass and dural margins. Histopathological diagnosis was Non-Hodgkin B-Cell lymphoma (marginal B-Cell lymphoma), which nowadays is considered as MALT lymphoma (Mucosa Associated Lymphoid Tissue). Studies directed to establish tumour extension didn't demonstrate the existence of another lesions in the organism.

Linfoma dural primario no Hodgkin B de bajo grado simulando un meningioma / Primary dural low grade non-Hodgkin B cell-lymphoma mimicking meningioma

Los linfomas meníngeos primarios son muy poco frecuentes, presentándose como lesiones difusas y siendo muy infrecuentes las masas bien delimitadas. Presentamos el caso de un paciente varón de 44 años de edad, que ingresa de Urgencias por presentar una crisis convulsiva generalizada. Se realizaron estudios de neuroimagen consistentes en TC, RNM y angiografía cerebral, que demostraron la presencia de una tumoración extraaxial bien delimitada en convexidad derecha, siendo el diagnóstico sospechado meningioma y siendo intervenido quirúrgicamente, con resección completa de la lesión y márgenes durales. El diagnóstico histopatológico correspondió a un linfoma B no Hodgkin de bajo grado (linfoma de células de zona marginal), actualmente considerado como linfoma MALT (Mucosa Associated Lymphoid Tissue). Los estudios destinados a establecer una extensión tumoral no demostraron la existencia de otras lesiones en el organismo (AU)

Digital image documentation for quality assessment.

OBJECTIVE: To demonstrate the feasibility of the use of digital images to document routine cases and to perform diagnostic quality assessment. METHODS: Pathologists documented cases by acquiring up to 12 digital images per case. The images were sampled at 25:1, 50:1, 100:1, 200:1, or 400:1 magnifications, according to adequacy in aiding diagnosis. After each acquisition, the referral pathologist marked a region of interest within each acquired image in order to evaluate intrinsic redundancy. The extrinsic redundancy was determined by counting the unnecessary images. Cases were randomly selected and reviewed by one pathologist. The quality of each image, the possibility of accomplishing a diagnosis based on images, and the degree of agreement was evaluated. RESULTS: During routine practice, 1469 cases were documented using 3902 images. Most of the images were acquired at higher power magnifications. From all acquired cases, 143 cases and their 373 related images were randomly selected for review. In 88.1% (126/143) of reviewed cases, it was possible to accomplish the diagnosis based on images. In 30.2% (38/126) of these cases, the reviewer considered that the diagnosis could be accomplished with fewer images. The referral pathologist and the reviewer found intrinsic redundancy in 57.8% and 54.5% of images, respectively. CONCLUSIONS: Our results showed that digital image documentation to perform diagnostic quality assessment is a feasible solution. However, owing to the impact on routine practice, guidelines for acquisition and documentation of cases may be needed.

Microvessel density counting in breast cancer. Slides vs. digital images.

OBJECTIVE: To develop a program to assist the pathologist in the acquisition and evaluation of digital images to determine microvessel density (MVD) in tissues. STUDY DESIGN: Ten cases of breast cancer with a high degree of neovascularization were selected. A standard immunohistochemical method was used to highlight the microvessels (monoclonal anti-factor VIII, avidinbiotin-peroxidase complex method). Two pathologists (one senior [S] and one junior [J]) evaluated four areas of highest neovascularization ("hot spots") in the tumors. Microscopically MVD was determined in four chosen areas (400:1). From the center of each area two digital images were acquired at a magnification of 200:1. All counts made by microscopic observation were compared with those made on the digital images. To compare MVD counting at different resolution, two sets of images at different sampling densities (320 x 240 and 1,600 x 1,200) were assessed by the two pathologists. RESULTS: We obtained a good correlation (r = .98 for S and .96 for J) between the MVD counts obtained at the microscope (192.8 MV/mm2 [mean of S] and 181.8 MV/mm2 [mean of J]) and the MVD counts from digital images (153.2 MV/mm2 [mean of S] and 171.0 MV/mm2 [mean of J]) at high resolution. The counts were lower for digital images at lower sampling density (125.0 MV/mm2 [mean of S] and 78.2 MV/mm2 [mean of J]). With low-resolution digital images only S maintained a good correlation (r = .96 for S and .34 for J) with the microscopic evaluation of MVD. Interobserver analysis showed a good correlation (r = .82 for the microscope and r = .78 for the digital images) of MVD evaluated either at the microscope or in high-resolution digital images. CONCLUSION: We demonstrated the functionality and usefulness of our program in performing MVD evaluation. Considering the capabilities of the program to store all images and microvessel marks and the reliability of MVD evaluation based on digital images, we consider this program the first step toward fully automated MVD assessment.

Identificación de nuevos marcadores citogenéticos con valor pronóstico en cáncer de mama / New cytogenetic prognostic markers in breast cancer

Fundamento. El objetivo del trabajo ha sido la caracterización de las alteraciones cromosómicas en una serie de 70 carcinomas de mama de tipo ductal invasivo. Para identificar nuevos marcadores citogenéticos con valor pronóstico se estudió la asociación entre las alteraciones cromosómicas, determinados factores anatomopatológicos y la supervivencia e incidencia de recidivas de las pacientes. Material y métodos. Se seleccionaron 70 tumores diagnosticados en el Hospital de Navarra entre 1991-1994. La técnica utilizada fue la Hibridación Genómica Comparada (CGH) aplicada a tejidos incluidos en parafina. Resultados. Se obtuvieron resultados satisfactorios en 57 de 70 muestras (81,4 por ciento). Las ganancias cromosómicas detectadas con mayor frecuencia afectaron a 8q, 17q, 1q, 20q, 11q, y 6q y las pérdidas más frecuentes fueron en 16q, X, 13q, 11q y 8p. Como factores pronósticos, las ganancias en 1q y 11q13 se mostraron significativamente asociadas a mayor incidencia de recidivas de las pacientes (41,3 por ciento vs 18,5 por ciento y 50 por ciento vs 23,7 por ciento). Las pérdidas en 16q resultaron ser el principal marcador citogenético con valor pronóstico: 100 por ciento de los tumores con pérdidas en 16q fueron positivos para la sobreexpresión de Bcl-2 y 75 por ciento no presentaron afectación ganglionar. Además, 46,7 por ciento de los casos positivos para la expresión de receptores de estrógenos también presentaron esta alteración. Conclusiones. La técnica de CGH es de gran utilidad para el estudio de tumores incluidos en parafina. Los resultados obtenidos confirman la conveniencia de considerar la determinación citogenética de las alteraciones presentes en el tumor como un posible factor pronóstico que contribuya a un mejor conocimiento de la evolución clínica del tumor. (AU)

Bronquiolitis obliterante con neumonía organizativa y Coxiella burnetii / Bronquiolitis obliterans with organising pneumonia and Coxiella burnetii

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[New cytogenetic prognostic markers in breast cancer]. / Identificación de nuevos marcadores citogenéticos con valor pronóstico en cáncer de mama.

BACKGROUND: The aim of this study was to identify chromosomal imbalances in a series of invasive ductal carcinomas. In order to characterize the prognostic value of the chromosomal aberrations, we determined the association between genetic changes, overall survival, recurrences and some well-known prognostic and diagnostic parameters. MATERIAL AND METHODS: We included in this study 70 ductal invasive carcinomas diagnosed at the Hospital of Navarra during 1991-1994. We used the Comparative Genomic Hybridization Technique (CGH) for the molecular cytogenetic analysis of formalin-fixed, paraffin embedded specimens. RESULTS: We obtained successful results in 57 out of 70 cases (81.4%). The most frequent recurring findings were DNA gains on 8q, 17q, 1q, 20q, 11q and 6q and losses on 16q, Xp, Xq, 13q, 11q and 8p. In the survival study, gains on 1q and 11q13 were more frequent in patients with recurrence (41.3% vs. 18.5% and 50% vs. 23.7%). Loss of 16q appears as a prognostic factor of good outcome because of its association with good pathological prognostic features: 100% of tumors with this aberration showed overexpression of Bcl-2, and 75% of them were node negative. Besides, 46.7% of the positive cases for the expression of estrogen receptors also showed this imbalance. CONCLUSIONS: The CGH is a useful technique for the study of paraffin embedded tumors. Our results confirm that the cytogenetic aberrations of tumors could be considered as prognostic factors contributing to a better knowledge of tumor outcome.

Effects of controlled breathing, mental activity and mental stress with or without verbalization on heart rate variability.

OBJECTIVES: To assess whether talking or reading (silently or aloud) could affect heart rate variability (HRV) and to what extent these changes require a simultaneous recording of respiratory activity to be correctly interpreted. BACKGROUND: Sympathetic predominance in the power spectrum obtained from short- and long-term HRV recordings predicts a poor prognosis in a number of cardiac diseases. Heart rate variability is often recorded without measuring respiration; slow breaths might artefactually increase low frequency power in RR interval (RR) and falsely mimic sympathetic activation. METHODS: In 12 healthy volunteers we evaluated the effect of free talking and reading, silently and aloud, on respiration, RR and blood pressure (BP). We also compared spontaneous breathing to controlled breathing and mental arithmetic, silent or aloud. The power in the so called low- (LF) and high-frequency (HF) bands in RR and BP was obtained from autoregressive power spectrum analysis. RESULTS: Compared with spontaneous breathing, reading silently increased the speed of breathing (p < 0.05), decreased mean RR and RR variability and increased BP. Reading aloud, free talking and mental arithmetic aloud shifted the respiratory frequency into the LF band, thus increasing LF% and decreasing HF% to a similar degree in both RR and respiration, with decrease in mean RR but with minor differences in crude RR variability. CONCLUSIONS: Simple mental and verbal activities markedly affect HRV through changes in respiratory frequency. This possibility should be taken into account when analyzing HRV without simultaneous acquisition and analysis of respiration.

Is TTF1 a good immunohistochemical marker to distinguish primary from metastatic lung adenocarcinomas?

To evaluate the immunohistochemical expression of thyroid transcription factor 1 (TTF1) in primary and metastatic pulmonary adenocarcinomas, and test the diagnostic accuracy of this antibody, two surgical pathologists independently evaluated 34 cases of adenocarcinomas in the lung without clinical data and tried to distinguish between primary and metastatic cases using histological criteria exclusively. Thirteen cases were primary in the lung and 21 were metastases of extrapulmonary adenocarcinomas: 6 from the endometrium, 4 from the ovary, 3 from the colon, 2 from the kidney, 2 from the breast, 2 from the liver and 1 from the prostate. Afterward, the immunoreactivity of TTF1 in these neoplasms was evaluated and correlated with morphological and clinical data. The two pathologists were able to diagnose only 5 out of 13 cases of primary lung adenocarcinomas (sensitivity of 38.46%) and also misdiagnosed two primary malignancies as metastases. After correlation with TTF1 data, the sensitivity increased to 61.53%. The specificity of TTF1 was 100%. In conclusion, TTF1 is a highly specific marker for primary lung adenocarcinomas, and should be included in a panel of antibodies for the differential diagnosis between primary and metastatic adenocarcinomas of the lung.