Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection.

Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

Waddlia chondrophila and Chlamydia trachomatis antibodies in screening infertile women for tubal pathology.

Since Waddlia chondrophila is closely related to Chlamydia trachomatis, we hypothesise that W. chondrophila may also be associated with tubal factor infertility (TFI) in women, a major complication of chronic C. trachomatis infection. Five hundred twenty serum samples were tested for anti-Waddlia antibodies by ELISA. Among the 520 investigated women, a total number of 142 (27.3%) has had laparoscopic diagnosis performed, and were either classified TFI positive or negative. Presence of high titres of W. chondrophila antibodies was linked to TFI (p < 0.0001; OR: 7.5; 95% CI: 3.3-17). Moreover, antibody positivity to both W. chondrophila and C. trachomatis-MOMP was strongly associated with TFI (p < 0.0001; OR: 21; 95% CI: 3.8-12E1). This association was much stronger than the statistical association of C. trachomatis-MOMP antibodies only (p < 0.0001; OR: 7.1; 95% CI: 3.7-14), suggesting that co-infection with W. chondrophila and C. trachomatis may lead to more severe reproductive sequelae and immune responses than single infection with either Chlamydiales members.

Role of immune and angiogenic markers in the pathology of endometriosis

Background: Endometriosis is an estrogen-dependent, pro-inflammatory, pro-angiogenic condition that affects 5 to 10% of women of reproductive age. Its defining feature is the presence of endometrium-like tissue in sites outside the uterine cavity, primarily on the pelvic peritoneum and ovaries. The main clinical features are chronic pain, pain during intercourse and infertility. In patients with endometriosis, inflammatory and immune responses, angiogenesis and apoptosis are altered in favour of the survival and replenishment of endometriotic tissue. These basic pathological processes depend on the excessive formation of estrogen and prostaglandins. Recently, new cellular and molecular mechanisms for the resolution of inflammation have been discovered, revealing key roles for lipid mediators such as lipoxins, resolvins and protectins. It is possible that disequilibrium in the expression of these molecules exists in endometriosis. Objective: To compare the expression of two proteins involved in the synthe sis and in the function of lipid mediators; the Arachidonate 15-lipoxygenase (ALOXI5), implicated in the synthesis of lipoxins A4 and B4 and the Formyl peptide receptor 1 (FPRLI), the specific receptor for Lipoxin A4 and B4, between women who suffer from endometriosis and a control group. We wish to demonstrate the cellular localisation of these two molecules and to investigate if their expression is alteted in this pathology. Methods and Materials Using immunohistochemistry we will compare ALOXI5 and FPRLI staining, in endometrium, normal peritoneum and endometriotic lesions. The samples are being collected in the department of Gynaecology and Obstetrics at the Centre Hospitalier Universitaire Lausanne (CHUV). Women attending the department for laparoscopic investigation of pain/infertility, suspected endometriosis or for a hysterectomy, are invited to participate. Approval of the ethics committee (Commission d'Ethique de la recherché clinique) was obtained in March 2009. Clinical samples will only be obtained from subjects having consented. Expected results and interpretation: No published studies investigating the expression of these two molecules in endometriotic lesions exist. A better understanding of the mechanisms underlying this disease will result in the development of new medical therapies and new diagnostic tests, with the aim of ameliorating the quality of life of endometriosis patients.

Communication skills in diagnostic pathology.

Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

Tamaño dental, desgaste oclusal y microestriación en primates Hominoidea

El patrón de microestriación dentaria depende no solo de la composición de los alimentos ingeridos, sino también de la presencia en ellos de polvo, cenizas u otras partículas abrasivas de origen externo, generalmente incorporadas al alimento durante su preparación. El presente estudio analiza cómo se ve afectado el patrón de microestriación de la superficie vestibular de los dientes por factores independientes a la estructura y composición alimentaria, como son el tamaño de la pieza dentaria y el desgaste oclusal de la misma. Se han analizado moldes dentarios obtenidos de ejemplares originales de colecciones osteológicas de molares de primates Hominoideos, en los que se ha medido el patrón de microestriación dentaria de todos los individuos, así como el tamaño dental (área oclusal total- AOT) y el desgaste oclusal (porcentaje de exposición de dentina- PED) mediante técnicas semiautomáticas de análisis cuantitativo. Los resultados obtenidos indican que el tamaño dentario y el grado de desgaste oclusal de los molares analizados no están correlacionados con el patrón de microdesgaste dental de sus superficies vestibulares. Ello sugiere que las actividades masticatorias asociadas con las superficies oclusales de los molares no están directamente relacionadas con la capacidad abrasiva del alimento, sino con utilización de la superficie occlusal de la dentición en actividades que no repercuten en el patrón de microestriación de las superficies vestibulares de los dientes.

Traumatic bone cyst: a retrospective study of 21 cases

Objective: To describe the clinical and radiological characteristics, and surgical findings of traumatic bone cysts. Study Design: A retrospective observational study was made of 21 traumatic bone cysts. The diagnosis was based on the anamnesis, clinical examination, and complementary tests. Panoramic and periapical X-rays were obtained in all cases, together with computed tomography as decided by the surgeon. A descriptive statistical analysis was made of the study variables using the SPSS v12.0 for Windows. Results: There was a clear female predominance (14:7). The mean age was 26.5 years (range 8-45 years). The cysts in all cases constituted casual findings during routine radiological exploration. In those cases where computed tomographic images were available, preservation of the vestibular and lingual cortical layers was observed. Five of the 21 patients (23.8%) reported a clear antecedent of traumatism in the affected zone. All the lesions were subjected to surgery, and the cavities were found to be vacant in 90.5% of the cases. In only two patients were vascular contents seen within the cavity. Two of the patients presented postoperative paresthesia of the inferior dental nerve that subsided within two weeks. The 19 patients in whom adequate postoperative follow-up proved possible all showed complete bone healing. Conclusions: Traumatic bone cysts were a casual finding. During the surgery, most cases showed to be vacant cavity without an ephitelial lining. Careful curettage of the lesion favors progressive bone regeneration, offering a good prognosis and an almost negligible relapse rate. Other treatment options only would be justified in cases of relapse.

Retrospective clinicopathological study of 418 odontogenic cysts

Objectives: To determine the relative incidence of odontogenic cysts and to identify the main clinicopathological features among patients treated in the Oral Surgery Department of the Dental Clinic of the University of Barcelona (Spain). Study design: A retrospective observational study was made of 418 odontogenic cysts diagnosed in 380 patients included in the database of 1235 histopathological diagnoses. The subjects were treated in the Master degree program of Oral Surgery and Implantology of the University of Barcelona in the period 1997-2006. The following variables were recorded: gender, age, clinical characteristics of the lesions (size and location), radiological features, duration, treatment, complications and relapses. A descriptive analysis was made of the study variables, using the SPSS version 15.0. Results: The incidence of odontogenic cysts was 33.8%. The mean patient age at appearance of the lesion was 42 years (range 7-83). The cysts were slightly more prevalent in males (58.4%). The lesion size ranged from 2-60 mm, with a mean size of 18.4 mm. The most frequent diagnosis was radicular cyst (50.2%). The most common location of the odontogenic cysts was in the mandible (61.5%), particularly the lower third molar region (36.8%). Conclusions: The most frequently diagnosed lesion was the radicular cyst. Odontogenic cysts were seen to be slightly more prevalent in males, and showed a high mandibular incidence. Knowledge of the biological and histological behavior of odontogenic cysts and their frequency are key aspects for ensuring early detection and adequate treatment.

Lateral periodontal cysts: a retrospective study of 11 cases

Objective: To describe the clinical, radiological and histopathological features of lateral periodontal cysts among patients diagnosed in different centers (Vall d"Hebron General Hospital, Granollers General Hospital, the Teknon Medical Center, and the Master of Oral Surgery and Implantology of the University of Barcelona Dental School; Barcelona, Spain). Study design: A retrospective observational study was made of 11 lateral periodontal cysts, all of which were diagnosed following a thorough clinical examination, radiological study and posterior histological study. Results: The mean patient age was 37 years, and males predominated over females. The mean lesion size was 1.25 cm. A single relapse was recorded 7 years after removal of the initial lesion. All the cysts were surgically removed. Discussion and conclusions: Lateral periodontal cysts are very infrequent, and are characterized by the preserved vitality of the adjacent teeth. Identification of the lesion is initially based on the clinical findings, though histological study is required to confirm the diagnosis. The treatment of choice is the surgical removal, though occasional relapses have been documented

Monomer conversion of composite dental resins photoactivated by a halogen lamp and a LED: a FT-Raman spectroscopy study

Eighteen circular blocks of resins cured either by a LED or a halogen lamp (20, 40 and 60 s), had their top (T) and bottom (B) surfaces studied using a FT-Raman spectrometer. Systematic changes in the intensity of the methacrylate C=C stretching mode at 1638 cm-1 as a function of exposure duration were observed. The calculated degree of conversion (DC) ranged from 45.0% (B) to 52.0% (T) and from 49.0% (B) to 55.0% (T) for the LED and halogen lamp, respectively. LED and halogen light produced similar DC values with 40 and 60 s of irradiation.

Antenatal inflammation and brain pathology in preterm infants

Chorioamnionitis is known to be an important risk factor underlying preterm delivery, and it has also been suggested to associate with brain lesions and deviant neurological development in both preterm and term infants. Cytokines are believed to be the link causing the deleterious effects of inflammation to the nervous system. Their genetic regulation has also been suggested to play a role, as interleukin (IL)-6 -174 and -572 genotypes, which partly regulate IL-6 synthesis responses, have been connected with deviant neurological development in preterm infants. We evaluated the association of histological chorioamnionitis with brain lesions, regional brain volumes, and the functioning of the auditory pathway in very low birth weight/very low gestational age (VLBW/VLGA) infants. In addition, we investigated the association between IL-6 -174 and -572 genotypes and histological chorioamnionitis, neonatal infections, and brain lesions and regional brain volumes in VLBW/VLGA infants. This study is a part of a larger multidisciplinary project PIPARI (Development and Functioning of Very Low Birth Weight Infants from Infancy to School Age), in which the survivors of a 6-year cohort of VLBW/VLGA infants (n=274) are being followed until school age in Turku University Central Hospital, Finland. Placental samples were collected in the delivery room, and were analyzed for histological inflammatory findings. Blood samples from the infants were collected and DNA was genotyped for IL-6-174 and -572 polymorphisms (GG/GC/CC). Brain ultrasound examinations were performed repeatedly in the neonatal intensive care unit and at term age, and were analysed for structural brain lesions. Brain magnetic resonance imaging was performed at term age, and was analysed for regional brain volumes. In addition, diffusion tensor imaging was performed at term, and was used to analyse fractional anisotrophy and the apparent diffusion coefficient of inferior colliculus. The brainstem auditory evoked potential recordings were carried out according to the routine clinical procedure at median age of 30 days after term age. In our study, we found that histological chorioamnionitis was not an independent risk factor for brain lesions, reduced regional brain volumes or abnormal functioning of the auditory pathway in VLBW/VLGA infants. In addition, we found that IL-6 -174 GG and -572 GC genotypes were associated with a higher incidence of histological chorioamnionitis, and that -174 CC genotype associated with higher incidence of septicaemia. The analysed IL-6 genotypes were not associated with other brain lesions, but a reduced volume of basal ganglia and thalami was associated with IL-6 -174 CC and -572 GG genotypes. In conclusion, our findings suggest that histological chorioamnionitis is not an independent risk factor for the brain development of VLBW/VLGA infants, or that the risk caused by inflammation does not exceed the risks attributed to other underlying pathologies behind preterm deliveries. In addition, our findings give reason to propose that IL-6 promoter genotypes have a role in the defence against serious infections and in the brain development of VLBW/VLGA infants.

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.