Maria Righi

Alemtuzumab therapy for refractory idiopathic hypereosinophilic syndrome with abnormal T cells: a case report.

A diagnosis of idiopathic hypereosinophilic syndrome was made in a 68-year-old woman in 2002. She was treated with hydroxycarbamide, interferon-a and imatinib (400 mg/d) without evidence of response. In November 2003 she was admitted to our department with anaemia, fever and several painful pruritic skin lesions (top). Immunophenotypic analysis of circulating lymphocytes showed an abnormal CD4 subset characterized by absent surface expression of the CD3 antigen (abnormal T cells have a CD3CD4 CD8 phenotype). Serum interleukin-5 (IL-5) concentration was 280 pg/mol (normal 10 pg/mol). Twodimensional Doppler echocardiography showed endocardial thickening; the left ventricular ejection fraction (LVEF) was 48%. A skin biopsy demonstrated a dermal infiltrate consisting primarily of eosinophils (bottom left). A diagnostic work-up including radiological evaluation failed to reveal an overt lymphoproliferative disorder. As a consequence of the previous demonstration that CD52 is expressed on human eosinophils, the patient was administered subcutaneous alemtuzumab in increasing doses of up to 30 mg weekly. Once commenced on alemtuzumab, her pyrexia settled and the cutaneous lesions started to resolve (bottom right), the LVEF improved to 61% and serum IL-5 concentration fell to 9 pg/mol. Currently, 6 months after the revised diagnosis, the patient is well with an eosinophil count of 0.3 · 10/l on alemtuzumab (30 mg) every 3 weeks.

Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature.

End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end-to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10–11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes.

The cerebellum-periaqueductal gray connectivity: a constrained spherical deconvolution tractography study

The periaqueductal gray (PAG) is a relevant neuronal station situated in the midbrain, which play a pivotal role in triggering behavioral responses to stressful stimuli, such as pain or threat. Current knowledge concerning PAG functions is based on several tract-tracing studies conducted on animals, which unveiled PAG connectivity to both cortical and subcortical areas [1]. Considering that descending projections to spinal cord reach the dorsal horn and connections to motor related cortical areas have never been described yet, the neural structure which best fits PAG modulation of motor behavior is the cerebellum. Direct connections between PAG and cerebellar cortex were firstly described in cats and neurophysiological studies conducted on animals, suggesting either direct or undirect PAG influence to cerebellar activity. In the last decades, the rise of diffusion weighted imaging and tractography have made possible to reliably reconstruct white matter pathways in the human brain. To the best of our knowledge, few tractography studies explored PAG connectivity in humans and the evidences concerning direct or undirect connections with the cerebellar cortex are still sparse. Aimed at investigating PAG connectivity with particular focus on PAG-cerebellum connections, we used high quality diffusion weighted imaging data of thirty healthy subjects from the Human Connectome Project. Fiber tracts have been reconstructed using Spherical Informed Filtering of Tractograms, a novel algorithm improving streamline reconstruction and selection [2]. Connectivity analysis revealed that the PAG is mainly connected with subcortical structures, such as the thalamus and the cerebellum. Taken together our results show a direct interplay between the PAG and the cerebellum, thus suggesting the cerebellum as a likely candidate to modulate complex features of motor behavior in stressful conditions, such as adaptation after social defeat and computing strategies to avoid threatening situations.

Finite Element Analysis in different Subtype of Sagittal Alignment

In humans, vertical posture acquisition caused several changes in bones and muscles which can be assumed as verticalization. It’s widely known that six different morphological categories exist; each category differs from the others by pelvic parameters and vertebral column curvatures. Both values depend on the Pelvic Incidence, calculated as the angle between the axis passing through the rotation centre of the two femur heads and the vertical axis passing through the superior plate of the sacrum. The aim of this study is to evaluate the distribution of stress and the resulting strain along the axial skeleton using finite element analysis. The use of this computational method allows performing different analyses investigating how different bony geometries and skeletal structures can behavior under specific loading conditions. A CT of artificial bones, was used to obtain geometrical data of the model developed. Lines were imported into a commercial code in order to interpolate main surfaces and create the solid version of the model. Six different models were created according Roussouly’s classification, by arranging geometrical position of the skeletal components. Loading conditions were obtained by applying muscular forces components to T1 to L5, and a fixed constrain was at the distal epiphisis of femurs. Materials were assumed as elastic; Elastic modulus of 15 GPa, a Shear Modulus of 7 GPa for bony parts; Elastic modulus of 6 MPa, a Shear Modulus of 3 MPa for cartilaginous parts [1]. Six different simulations have been carried out. Results confirm higher solicitations obtained varying configurations from case I to case VI. In particular way, first three cases seem to supply the different loading configurations spreading stresses in almost all the bony parts of the column, while the remaining others three cases produce a higher concentration of stress around the lower part of spine (L3, L4, L5). Results confirm a good agreement with those present in literature, an equivalent Von Mises average stress of 0,55 MPa was found on the intervertebral disks with the higher values reached on the lower part of the model. A comparison of results obtained for Case I with literature, shows a good agreement in terms of normal compressive force, while more evident differences can be found for shear force and sagittal moment. The results underline a relationship between PI increase, and accordingly of PT and LL, and the distribution of load forces. Load forces is exerted mainly on distal vertebrae, especially on L4 and L5.

Morphological and protein expression aspects of masseter muscle fibers and extracellular matrix in malocclusion disease.

Unilateral posterior crossbite is an asymmetric malocclusion characterized by an inverse relationship of the upper and lower buccal dental cusps on one side only of the dental arch. Patients with unilateral posterior crossbite exhibit altered coordination of the masseter muscles during mastication. Changes in masticatory musculature structure and function may be either developmental or adaptive (1) and they depend on the remodeling processes of muscle fibers and connective tissue (2). The aim here was to investigate morphological and protein expression aspects of masseter muscle fibers and of extracellular matrix in malocclusion disease. Three patients, affected by unilateral posterior crossbite, were recruited to participate in this study; biopsies of masseter muscle have been withdrawn from left and right sides for each patients. We performed histological colorations and immunofluorescence reaction using antibody against Myf-5, MyoD, fibronectin, collagen I, III, IV and laminin. Results of crossbite side have shown altered fibers morphology, consistent increase of extracellular matrix and its proteins; a lower number of Myf-5 and MyoD positive cells than contralateral side has been observed. In contralateral side we observed normal muscle fibers and extracellular matrix morphology, a lower expression of extracellular matrix proteins and an higher number of Myf-5 and MyoD positive cells than crossbite side. These findings suggest us that in contralateral side, the high workload determines an hypertrophic response of muscle fibers, evidenced by the high number of Myf-5 and MyoD positive cells and probably an increased turnover of extracellular matrix which is poorly represented; the crossbite side muscle, instead, seems to show alterations of the remodeling processes as evidenced by the reduction of fibers dimension in favor of an increase of the extracellular matrix components. That could be relevant in understanding and healing of malocclusion disorders.

Three-dimensional analysis for the evaluation of left ventricular aneurysm and pseudo-aneurysm after myocardial infarction

Myocardial Infarction (MI) is an ischemic heart disease representing one of the main causes of death for acute cardiac pathologies. Two important consequences of MI are left ventricular (LV) aneurysm and pseudo-aneurysm. The aim of the present study is to highlight anatomical and functional changes in LV undergoing post-ischemic remodeling by means of three dimensional-Magnetic Resonance Imaging (MRI) and three dimensional-Computed Tomography (CT), which are useful techniques for the diagnosis and evaluation of accurate clinical and surgical approaches. In this way the surgeon can evaluate pro and counter of the classical approach or the parachute implant with possible promotion of mininvasive surgery [1]. Although to date MI consequences can be assessed with bidimensional technique (e.g. echocardiography and ventriculography), we want to suggest the use of three dimensional Direct Volume Rendering (DVR), which is a direct technique for visualizing primitive volumes without any intermediate conversion of the volume data to surface presentation [2]. DVR allows to better discriminate between aneurysm and pseudoaneurysm and to do a better evaluation of inclusion and exclusion criteria for the implant of a parachute device.

A study of the olfactory tract with 3D rendering, f-MRI and CSD fiber tractography in healty and PD subjects

In this study we report an optimized single-shot diffusion-weighted echo planar imaging sequence that can visualize the olfactory tracts with CSD fiber tracking, 3D volume rendering and f-MRI. The olfactory tracts are localized in the olfactory grooves of the ethmoidal bone, running posteriorly through the olfactory sulci connecting to the inferior surfaces of the frontal lobes. Distally the tracts are enlarged into the olfactory bulbs and proximally they split into medial, intermediate and lateral striae and from here the axon projecting to the olfactory cortex, divided into five main areas: the anterior olfactory nucleus, which connects the two olfactory bulbs through a portion of the anterior commissure; the piriform cortex; parts of the amigdala, the olfactory tubercle and entorinal cortex; not all of these connections through the thalamus. Moreover, olfactory information is transmitted from the amygdala to the hypothalamus and from the entorinal area to the hippocampus.The olfactory tracts are difficult to depict with MRI diffusion-weighted imaging due to the high sensitivity to susceptibility artifacts at the base of the skull (Duprez and Rombaux, 2010). Ten subjects were examined; in five healthy subjects the olfactory tracts could be fiber tracked with the diffusion-weighted sequence, while in five anosmic PD patients, altered olfactory tracts were visualized. Furthermore, olfactory stimuli were applied during fMRI scanning to show the area BOLD activation to advance our understanding of olfactory dysfunction in PD patients compared to control. Olfactory function was established using the “Sniffin’ Sticks” test battery.This study of the olfactory tracts promise to visualize the anatomic organization and to facilitate the identification of different hyposmic and anosmic entities caused by neurodegenerative disorders or post-traumatic and congenital disfunctions.

DT-MRI study on masticatory muscles in normal and pathological subjects

In our recent research we tested the use of DTI in the study of muscles, considering anatomical and clinical application. We have demonstrated the possibility to detect even minor muscle injuries of athletes undetectable with traditional ultrasound techniques. In this report we intend to apply this method to the study of the anatomical and volumetric masticatory muscles and particularly of masseter muscle. We selected a sample of 5 healthy subjects and 5 patients with cross-bite. Our results demonstrate the possibility to distinguish, on the basis of the different orientation of the muscle fibers, masseter muscles from pterygoid muscles. In addition, with post-elaboration of DTI anisotropy map, we evaluated different masticatory muscles density revealing their reduction along cross-bite side and a light increment in contralateral muscle. These evidences confirm our previous results obtained with elettromiography and histochemistry techniques.