Detection of gelatinolytic activity in developing basement membranes of the mouse embryo head by combining sensitive in situ zymography with immunolabeling

Genetic evidence indicates that the major gelatinases MMP-2 and MMP-9 are involved in mammalian craniofacial development. Since these matrix metalloproteinases are secreted as proenzymes that require activation, their tissue distribution does not necessarily reflect the sites of enzymatic activity. Information regarding the spatial and temporal expression of gelatinolytic activity in the head of the mammalian embryo is sparse. Sensitive in situ zymography with dye-quenched gelatin (DQ-gelatin) has been introduced recently; gelatinolytic activity results in a local increase in fluorescence. Using frontal sections of wild-type mouse embryo heads from embryonic day 14.5-15.5, we optimized and validated a simple double-labeling in situ technique for combining DQ-gelatin zymography with immunofluorescence staining. MMP inhibitors were tested to confirm the specificity of the reaction in situ, and results were compared to standard SDS-gel zymography of tissue extracts. Double-labeling was used to show the spatial relationship in situ between gelatinolytic activity and immunostaining for gelatinases MMP-2 and MMP-9, collagenase 3 (MMP-13) and MT1-MMP (MMP-14), a major activator of pro-gelatinases. Strong gelatinolytic activity, which partially overlapped with MMP proteins, was confirmed for Meckel's cartilage and developing mandibular bone. In addition, we combined in situ zymography with immunostaining for extracellular matrix proteins that are potential gelatinase substrates. Interestingly, gelatinolytic activity colocalized precisely with laminin-positive basement membranes at specific sites around growing epithelia in the developing mouse head, such as the ducts of salivary glands or the epithelial fold between tongue and lower jaw region. Thus, this sensitive method allows to associate, with high spatial resolution, gelatinolytic activity with epithelial morphogenesis in the embryo.

Asymptomatic ossifying fibroma of the mandible: a case presentation

Ossifying fibromas are rare benign bone-related lesions of the jaw. Early diagnosis based on clinical, radiologic, and pathohistologic findings is essential, since undetected lesions may expand and cause considerable functional and cosmetic problems. The treatment of choice is purely surgical. Periodic clinical and radiologic follow-up should be scheduled, since recurrence is possible. The present article describes the diagnostic procedures, surgical management, and follow-up of an asymptomatic ossifying fibroma in the mandible of a 21-year-old man.

Patients' awareness of the potential benefit of smoking cessation. A study evaluating self-reported and clinical data from patients referred to an oral medicine unit

The present study analyzed history of smoking and willingness to quit smoking in patients referred for diagnosis and treatment of different oral mucosal lesions. Prior to the initial clinical examination, patients filled in a standardized questionnaire regarding their current and former smoking habits and willingness to quit. Definitive diagnoses were classified into three groups (benign/reactive lesions, premalignant lesions and conditions, and malignant diseases) and correlated with the self-reported data in the questionnaires. Of the 980 patients included, 514 (52%) described themselves as never smokers, 202 (21%) as former smokers, and 264 (27%) as current smokers. In the group of current smokers, 23% thought their premalignant lesions/conditions were related to their smoking habit, but only 15% of the patients with malignant mucosal diseases saw that correlation. Only 14% of the smokers wanted to commence smoking cessation within the next 30 days. Patients with malignant diseases (31%) showed greater willingness to quit than patients diagnosed with benign/reactive lesions (11%). Future clinical studies should attempt (1) to enhance patients' awareness of the negative impact of smoking on the oral mucosa and (2) to increase willingness to quit in smokers referred to a dental/oral medicine setting.

Intraoperative determination of the load-displacement behavior of scoliotic spinal motion segments: preliminary clinical results

Introduction: Spinal fusion is a widely and successfully performed strategy for the treatment of spinal deformities and degenerative diseases. The general approach has been to stabilize the spine with implants so that a solid bony fusion between the vertebrae can develop. However, new implant designs have emerged that aim at preservation or restoration of the motion of the spinal segment. In addition to static, load sharing principles, these designs also require a profound knowledge of kinematic and dynamic properties to properly characterise the in vivo performance of the implants. Methods: To address this, an apparatus was developed that enables the intraoperative determination of the load–displacement behavior of spinal motion segments. The apparatus consists of a sensor-equipped distractor to measure the applied force between the transverse processes, and an optoelectronic camera to track the motion of vertebrae and the distractor. In this intraoperative trial, measurements from two patients with adolescent idiopathic scoliosis with right thoracic curves were made at four motion segments each. Results: At a lateral bending moment of 5 N m, the mean flexibility of all eight motion segments was 0.18 ± 0.08°/N m on the convex side and 0.24 ± 0.11°/N m on the concave side. Discussion: The results agree with published data obtained from cadaver studies with and without axial preload. Intraoperatively acquired data with this method may serve as an input for mathematical models and contribute to the development of new implants and treatment strategies.

Femoral morphology and epiphyseal growth plate changes of the hip during maturation: MR assessments in a 1-year follow-up on a cross-sectional asymptomatic cohort in the age range of 9-17 years

The goal of this prospective study was to characterize the morphology and physeal changes of the femoral head during maturation using MRI in a population-based group of asymptomatic volunteers.

Compartments of the foot: topographic anatomy

Recent publications have renewed the debate regarding the number of foot compartments. There is also no consensus regarding allocation of individual muscles and communication between compartments. The current study examines the anatomic topography of the foot compartments anew using 32 injections of epoxy-resin and subsequent sheet plastination in 12 cadaveric foot specimens. Six compartments were identified: dorsal, medial, lateral, superficial central, deep forefoot, and deep hindfoot compartments. Communication was evident between the deep hindfoot compartment and the superficial central and deep central forefoot compartments. In the hindfoot, the neurovascular bundles were located in separate tissue sheaths between the central hindfoot compartment and the medial compartment. In the forefoot, the medial and lateral bundles entered the deep central forefoot compartment. The deep central hindfoot compartment housed the quadratus plantae muscle, and after calcaneus fracture could develop an isolated compartment syndrome.

Anticancer drug vinblastine sulphate induces transient morphological changes on the olfactory mucosa of the rabbit

Vinblastine sulphate (VBS) is an anticancer drug that acts by disrupting microtubule dynamics of highly mitotic tissue cells. The consequences of VBS on the olfactory mucosa (OM), a tissue with high mitotic numbers, are not clearly understood. We used qualitative and quantitative methods to determine the structural changes that may be produced on the rabbit OM by VBS. Following a single dose (0.31 mg/kg) of this drug, the structure of the mucosa was greatly altered on the first 3-5 days. The alteration was characterized by disarrangement of the normal layering of nuclei of the epithelia, degeneration of axonal bundles, occurrence of blood vessels within the bundles, localized death of cells of Bowman's glands and glandular degeneration. Surprisingly on or after day 7 and progressively to day 15 post-exposure, the OM was observed to regenerate and acquire normal morphology, and the vessels disappeared from the bundles. Relative to control values, bundle diameters, olfactory cell densities and cilia numbers decreased to as low as 53.1, 75.2 and 71.4%, respectively, on day 5. Volume density for the bundles, which was 28.6% in controls, decreased to a lowest value of 16.8% on day 5. In contrast, the volume density for the blood vessels was significantly lower in controls (19.9%) than in treated animals at day 2 (25.8%), day 3 (34.3%) and day 5 (31.5%). These findings suggest that the changes induced on the rabbit OM by VBS are transient and that regenerative recovery leads to the restoration of the normal structure of the mucosa.

Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial

This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.

Validity and responsiveness of the Core Outcome Measures Index (COMI) for the neck

Patient-orientated outcome questionnaires are essential to evaluate treatment success. To compare different treatments, hospitals, and surgeons, standardised questionnaires are required. The present study examined the validity and responsiveness of the Core Outcome Measurement Index for neck pain (COMI-neck), a short, multidimensional outcome instrument.

Predictive value of the Acute Low Back Pain Screening Questionnaire and the Örebro Musculoskeletal Pain Screening Questionnaire for persisting problems

A small proportion of individuals with non-specific low back pain (NSLBP) develop persistent problems. Up to 80% of the total costs for NSLBP are owing to chronic NSLBP. Psychosocial factors have been described to be important in the transition from acute to chronic NSLBP. Guidelines recommend the use of the Acute Low Back Pain Screening Questionnaire (ALBPSQ) and the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) to identify individuals at risk of developing persistent problems, such as long-term absence of work, persistent restriction in function or persistent pain. These instruments can be used with a cutoff value, where patients with values above the threshold are further assessed with a more comprehensive examination.

Clinical study of mucosa-associated lymphoid tissue lymphomas of the head and neck

Background: Limited information is available on mucosa-associated lymphoid tissue lymphomas arising in the head and neck. Method: A retrospective analysis was conducted of 20 patients who were histologically diagnosed with mucosa-associated lymphoid tissue lymphoma and treated at our institution between January 1990 and December 2009. Results: Treatment consisted of surgical resection alone in two patients (10 per cent), surgical resection with consecutive radiotherapy in one (5 per cent), and radiotherapy alone in eight (40 per cent). Three patients (15 per cent) were treated with systemic chemotherapy, and three (15 per cent) received chemoradiotherapy. Three patients (15 per cent) were informed of the diagnosis but not treated for their condition. Conclusion: All of the 20 patients were still alive after a mean follow-up period of 50.8 months. Local treatment for mucosa-associated lymphoid tissue lymphoma of the head and neck should be the first choice in early-stage disease. However, prolonged follow up is important to determine these patients' long-term response to treatment.