Effects of zoledronic acid and dexamethasone on early phases of socket healing after tooth extraction in rats: A preliminary macroscopic and microscopic quantitative study.

BACKGROUND: The exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is still unknown. The aim of this paper was to investigate the effects of zoledronic acid and dexamethasone on the early phases of socket healing in rats subjected to tooth extractions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into 2 groups: pharmacologically treated group (T, n=20) and non-pharmacologically treated group (C, n=10). T group rats received 0.1 mg/Kg of zoledronic acid (ZOL) and 1 mg/Kg of dexamethasone (DEX) three times a week for 10 consecutive weeks. C group rats were infused with vehicle. After 9 weeks from the first infusion, first maxillary molars were extracted in each of the rats. Quantitative macroscopic and microscopic analysis was performed to evaluate socket healing 8 days after extraction. RESULTS: Pharmacologically treated rats showed significant inhibition of bone remodeling. Connective tissue/alveolar bone ratio, osteoclast number and woven bone deposition were significantly reduced in group T compared to group C. Conversely, the proportion of necrotic bone was higher in group T compared to group C (0.8% and 0.3%, respectively. P=0.031). ZOL plus DEX do not cause gross effects on socket healing at a macroscopic level. CONCLUSIONS: Our findings confirmed that exposure to ZOL plus DEX impairs alveolar wound repair. Inhibition of osteoclastic resorption of socket walls after tooth extraction and the inability to dispose of the necrotic bone may be considered the initial steps of MRONJ onset.

Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart.

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's "pinwheel experiment," usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array, and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1-ms cathodal stimuli at multiple test sites (n = 26) in seven rats. Stimulus-induced virtual electrode polarization during sinus beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break, and graded-response stimulation mechanisms. Hence unidirectional conduction block occurred as follows: 1) along fiber direction, on right and left ventricular free walls (n = 23), initiating figure-eight reentry (n = 17) and tachycardia (n = 12), and 2) across fiber direction, on lower interventricular septum (n = 3), initiating spiral wave reentry (n = 2) and tachycardia (n = 1). Critical time window (55.1 ± 4.7 ms, 68.2 ± 6.0 ms) and stimulus strength lower limit (4.9 ± 0.6 mA) defined vulnerability to reentry. A novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response (n = 13) characterized by focal activations.NEW & NOTEWORTHY We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.

PKCε is a negative regulator of PVAT-derived vessel formation.

RATIONALE: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive. OBJECTIVE: Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis. METHODS AND RESULTS: Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1. CONCLUSION: PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.

Benefits of 3D technique in guiding percutaneous retroperitoneal biopsies.

PURPOSE: This study aimed to assess the usefulness and advantages of multiplanar reformations (MPR) during multidetector-row computed tomography (MDCT)-guided percutaneous fine-needle aspiration biopsy (FNAB) and core biopsy of retroperitoneal lesions that are difficult to access with the guidance of ultrasound and axial CT alone owing to overlying bony structures, large vessels or abdominal organs. MATERIALS AND METHODS: MDCT-guided retroperitoneal FNAB and core biopsy was performed on 14 patients with suspected retroperitoneal neoplasm. We used MPR images (sagittal and coronal) obtained with a six-detector-row MDCT scanner and 20-22 gauge Chiba needles. RESULTS: Using MDCT with 3D MPR allowed biological samples to be obtained in all cases (ten cytological and four histological) and diagnostic samples in 11/14 cases (78.5%). Histological samples were deemed adequate for diagnostic assessment in all cases and cytological samples in 7/10 cases (70%). CONCLUSIONS: MPR images allowed sampling of retroperitoneal lesions until now considered unreachable with the guidance of axial MDCT alone. Compared with the conventional procedure, the use of MPR images does not increase the procedure time.

Chronic periaortitis associated with membranous nephropathy: clues to common pathogenetic mechanisms.

Chronic periaortitis (CP) is a rare disease hallmarked by the presence of a periaortic retroperitoneal fibro-inflammatory tissue which can often cause obstructive uropathy. CP is isolated in most cases but it may also be associated with other sclerosing inflammatory and immune-mediated diseases. We here present the case of a patient who was initially diagnosed as having CP and subsequently developed membranous nephropathy and chronic sclerosing sialoadenitis of the right parotid gland. As these conditions were all characterized by either pronounced infiltration of IgG4-positive plasma cells or marked IgG4 tissue deposition, we hypothesize that they are part of the same disease spectrum, and discuss the immune-mediated pathogenetic mechanisms potentially shared by these conditions. In particular, we consider the role of Th2-mediated immune reactions and of immunogenetic factors such as HLA genotype as common determinants of these disorders.

Multidetector computed tomography arthrography of the shoulder: diagnostic accuracy and indications.

BACKGROUND: The presence of subcutaneous implants, such as permanent defibrillators, is an absolute contraindication to the use of magnetic resonance imaging (MRI). Moreover, MRI is unadvisable in subjects with metallic hardware near the area of study, as artifacts generated by such materials distort image quality. PURPOSE: To evaluate the diagnostic accuracy and indications of arthrography with multidetector computed tomography arthrography (arthro-MDCT) of the shoulder in patients with absolute or relative contraindications to MRI and in patients with periarticular metal implants using diagnostic arthroscopy as the gold standard. MATERIAL AND METHODS: After intraarticular injection of iodixanol and volumetric acquisition, 70 shoulders in 70 patients (30 females, 40 males, age range 32-60 years) were examined with a 16-detector-row CT scanner. The patients had arthralgia but no radiologically detected fractures. They could not be studied by MRI because of absolute contraindications (subcutaneous electronic implants), surgical metal implants, or claustrophobia. In 28 of the 70 patients who had had previous shoulder surgery, the arthro-CT examination was preceded by an MRI on the same day. All examinations were interpreted by two experienced musculoskeletal radiologists. The findings were compared with arthroscopic findings carried out within 28 days of the CT study. RESULTS: In the 42 non-operated patients, the comparison between arthro-MDCT and arthroscopy showed sensitivity and specificity ranging between 87% and 100%. In the 28 operated shoulders, arthro-MDCT had an accuracy of 94% compared with 25% with MRI. Interobserver agreement was almost perfect (kappa=0.95) in the evaluation of all types of lesions, both on MDCT and MRI. When arthro-MDCT was compared with MRI in the postoperative patients by a McNemar test, a significant difference (P<0.05) was found between these two techniques. CONCLUSION: Arthro-MDCT of the shoulder is a safe technique that provides accurate diagnosis in identifying chondral, fibrocartilaginous, and intraarticular ligamentous lesions in patients who cannot be evaluated by MRI, and in patients after surgery.

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Gender differences and aging: effects on the human heart.

OBJECTIVES: This study investigated the changes in myocyte size and number in the left and right ventricles that occur with aging in the female and male heart. BACKGROUND: Differences in life span between women and men may be related to a better preservation of myocardial structure in the female heart with aging. On this basis, the hypothesis was advanced that the aging process has a different impact on the integrity of the myocardium in the two genders. METHODS: Morphometric methodologies were applied to analyze the changes in number and size of ventricular myocytes in the hearts of 53 women and 53 men. The changes in mononucleated and binucleated myocytes with age were determined in enzymatically dissociated cells. The age interval examined varied from 17 to 95 years. RESULTS: Aging was associated with a preservation of ventricular myocardial mass, aggregate number of mononucleated and binucleated myocytes, average cell diameter and volume in the female heart. In contrast, nearly 1 g/year of myocardium was lost in the male heart, and this phenomenon accounted for the loss of approximately 64 million cells. This detrimental effect involved the left and right sides of the heart. In the remaining cells, myocyte cell volume increased at a rate of 158 microns3/year in the left and 167 microns3/year in the right ventricle. CONCLUSIONS: Aging does not lead to myocyte cell loss and myocyte cellular reactive hypertrophy in women, indicating that gender differences may play a significant role in the detrimental effects of the aging process on the heart.

Langerhans-cell histiocytosis: a clinical case without bone involvement.

BACKGROUND: Langerhans-cell histiocytosis (LCH) is a group of rare disorders histologically characterized by the proliferation of Langerhans cells. Multiple organs and systems may be involved by the disease. Typically, there is bone involvement and, less frequently, lesions may be found in the lungs, liver, lymph nodes, skin, and mucosae. Oral soft tissue lesions without bone involvement are rare. METHODS: We report a case of a 23-year-old man with LCH detected by oral soft tissue, cutaneous, and lung lesions. RESULTS: Due to the oral lesion diagnosis, important procedures were performed, which determined the staging of the disease. CONCLUSION: Gingival lesions could be one of the first manifestations of LCH. The periodontist should recognize and detect this important pathology with oral involvement.

Idiopathic and secondary forms of retroperitoneal fibrosis: a diagnostic approach.

Retroperitoneal fibrosis (RPF) is an uncommon disease characterized by a fibrous reaction that takes place in the peri-aortic retroperitoneum and often entraps the ureters causing obstructive uropathy. RPF is idiopathic in the majority of cases, but can also be secondary to malignancies, infections, drugs, radiotherapy, and rare histiocytic disorders such as Erdheim-Chester disease. Idiopathic RPF is an immune-mediated disease, which can either be isolated, associated with other autoimmune diseases, or arise in the context of a multifocal fibro-inflammatory disorder recently renamed as IgG4-related disease. The differential diagnosis between idiopathic, IgG4-related and secondary RPF is crucial, essentially because the therapeutic approaches - especially of idiopathic vs. secondary RPF - can be dramatically different. This review focuses on the clinical, laboratory and imaging features of the different RPF forms, and also provides an overview of the available treatment options.

Styrene-induced changes in amacrine retinal cells: an experimental study in the rat.

Dopamine (DA) is synthesized in amacrine cells and released upon membrane depolarization in a calcium-dependent way. Thus, it is recognized to function as a major neurotransmitter or modulator in vertebrate retina. Owing to DA modulating activity on cone-horizontal cells transmission, depletion or dysfunction of amacrine cells could interfere with chromatic processing, accounting for the acquired dyschromatopsia described among styrene-exposed workers. The present study has been designed to test the hypothesis that amacrine cells represent a vulnerable target of styrene in subchronically exposed rats. Ten female Sprague-Dawley rats were exposed to 300 ppm styrene 6 h/day, 5 days/week, for 12 weeks; ten rats exposed to fresh air served as a control group. Whole mounted retinas were used for the morphometry of tyrosine hydroxylase (TH) immunoreactive cells (IR). DA content and TH activity were measured by HPLC and electrochemical detection and glutathione (GSH) was measured by HPLC tandem mass spectrometry (LC-MS/MS). In treated rats, morphometric analysis showed a loss of TH-IR amacrine cells (6.2/mm2 vs. 8.7/mm2 recorded in controls, p = 0.002), without any peripheral-central variation in cell loss. DA content was also lower in exposed, as compared to control animals (208.64 vs. 267.98 microg/g w.w., p = 0.004). The activity of TH in the whole retina was similar in styrene-exposed and control rats when expressed as a function of the wet weight, whereas it was much higher in styrene-exposed rats (+64%) when expressed as a function of the number of TH-IR amacrine cells (p < 0.001). Finally, retinal GSH was reduced by 30% in exposed as compared to control rats (p = 0.01). In summary, retinal TH-IR cells were sensitive to styrene exposure, which seems to cause both structural and functional changes, represented by cell loss and DA depletion, respectively. These findings confirm the vulnerability of dopaminergic systems to styrene toxicity, providing some insights on the possible mechanism of loss in chromatic discrimination recorded among workers occupationally-exposed to styrene.

Hand-assisted laparoscopic splenectomy for a splenic hamartoma.

We present a patient with a hamartoma of the spleen. The case was thought to be a good indication for a hand-assisted laparoscopic approach and treatment was successful. Until now, only one case of a laparoscopic removal of a splenic hamartoma has been reported. Focal lesions of the spleen should be removed intact to allow a complete histological examination and to avoid peritoneal dissemination in case of malignancy. In these patients, the hand-assisted approach makes possible the removal of an unminced organ and has the advantage of being a purely laparoscopic technique. It should thus be considered the method of choice for surgical treatment.

Role of intra-operative sentinel lymph node biopsy in oral cavity and oropharynx squamous cell carcinoma: preliminary data.

In patients with squamous cell carcinoma of the oral cavity and oropharynx, the presence of latero-cervical lymph node metastases was found to be the most important of the better known prognostic factors. Still, today, the most reliable technique by which to detect the presence of lymph node metastases is surgery aimed at the dissection of the latero-cervical space; albeit, this surgical procedure has been shown to be an over-treatment in a large percentage of patients presenting squamous cell carcinoma, clinically, radiologically and histologically negative, at neck level. The technique of intra-operative biopsy of sentinel lymph node, routinely used in the staging and treatment of tumours with elective lymphatic involvement such as carcinoma of the breast and malignant cutaneous melanoma, has progressively caught the attention of head and neck surgeons in the most important referral centres in the world, and, indeed, its role has been hypothesised in the treatment of patients with squamous cell carcinoma of the oral cavity and oropharynx with clinically N0 neck. Preliminary results are reported, concerning the use of this intraoperative sentinel lymph node biopsy technique with double tracer in patients presenting squamous cell carcinoma originating in the mucosa of the upper air-digestive tract, clinically and radiologically free from disease at latero-cervical level.

[Idiopathic retroperitoneal fibrosis]. / La fibrosi retroperitoneale idiopatica.

Retroperitoneal fibrosis is an uncommon disease, characterized by the replacement of normal retroperitoneal tissue with fibrosis and/or chronic inflammation. In two thirds of the cases retroperitoneal fibrosis is idiopathic (IRF), whereas in the remaining ones it is secondary/associated to cancer, infections, drugs, autoimmune disease and vasculitis. IRF appears as a dense, fibrous plaque that usually arises between the level of the lower aorta and the common iliac arteries. As the plaque progresses, it engulfs the adjacent structures (e. g., ureters). In its early stages IRF is characterized by a rich infiltrate of lymphocytes, plasma cells and macrophages interspersed within fibroblasts and collagen bundles. In its advanced stages it becomes relatively avascular and acellular with abundant collagen bundles and scattered calcifications. The pathogenesis is unknown: some Authors suggest that IRF is a consequence of a local autoimmune reaction against atherosclerotic plaque antigens whereas others propose that it is the manifestation of a systemic autoimmune disease. The presenting signs and symptoms are non-specific; systemic manifestations (fever, anorexia, weight loss), often associated with local symptoms, are usually found to be related to the entrapment of retroperitoneal structures. The most common local symptom is lumbar and/or abdominal pain. The treatment can be surgical and/or medical: the former is required when obstructive complications are present; the latter, associated or not with surgery, can significantly improve the outcome of IRF patients and usually modifies the natural history of the disease. Steroids and tamoxifen are the most used drugs, whereas other agents such as azathioprine, methotrexate and cyclosporine are usually given to non-responder patients.

Congenital anomalies and variations of the bile and pancreatic ducts: magnetic resonance cholangiopancreatography findings, epidemiology and clinical significance.

PURPOSE: The objective of this paper is to document the magnetic resonance cholangiopancreatography (MRCP) findings and the epidemiology of congenital anomalies and variations of the bile and pancreatic ducts and to discuss their clinical significance. MATERIALS AND METHODS: Three-hundred and fifty patients of both sexes (150 females, 200 males, age range 0-76 years, average age 38 years) underwent MRCP for clinically suspected lithiasic, neoplastic or inflammatory disease of the bile and pancreatic ducts. Patients were imaged with a 1.5-T superconductive magnet (Magnetom Vision, Siemens, Erlangen, Germany), a four-channel phased-array body coil, breath-hold technique, with multislice T2-weighted half-Fourier acquisition single-shot turbo spin echo (HASTE), MIP reconstructions, and a single-shot T2-weighted turbo-spin-echo sequence rapid acquisition with relaxation enhancement (RARE) with different slice thicknesses. Studies in oncological patients were completed with fat saturation 3D T1 gradient-echo sequences during the intravenous injection of gadolinium diethylene triamine pentaacetate acid (DTPA) (0.2 ml/kg). RESULTS: MRCP demonstrated recurrent and therefore normal bile and pancreatic ducts in 57% of patients. In the remaining 42.3%, it documented anatomical variants (41%) and congenital anomalies (1.3%). Variants of the intrahepatic bile duct were seen in 21% of cases: crossover anomaly (6.7%), anterior branch of the right hepatic duct draining the IV and VII segments that flow together with the left bile duct (3.1%) and anterior and posterior branches of the right hepatic duct that flow together with the common hepatic duct (3.3%). Variants of the extrahepatic bile ducts were present in 8.8% of patients: low insertion of the cystic duct into the common hepatic duct (4.5%), emptying of the cystic duct into the right hepatic duct (2.7%) and a second-order large branch draining into the cystic duct (1.6%). MRCP identified a double gall bladder in 3% of patients and anatomical variants of the biliopancreatic system in 8.2%: pancreas divisum (5.2%) and a long sphincter of Oddi (3%). Finally, congenital anomalies were diagnosed in 1.3% of cases: bile duct cysts (0.3%), atresia of the bile ducts (0.3%) and multiple biliary hamartomatosis (0.7%). CONCLUSIONS: The congenital anomalies and anatomical variants of the bile and pancreatic ducts present a complex spectrum of frequent alterations, which are worthy of attention in both the clinical and surgical settings and are readily identified by MRCP.

[Surgical management of orbital malignant melanoma: our experience and a report of three cases]. / Chirurgische Behandlung des malignen Orbita-Melanoms: unsere Erfahrung und ein Bericht über drei Fälle.

PURPOSE: The aim of this study is to illustrate our personal experience concerning the diagnostic and therapeutic management of primary and secondary orbital melanomas. PATIENTS AND METHODS: Nine patients (five men and four women) with a histological diagnosis of orbital malignant melanoma were surgically treated in our department during the last 10 years (1995 - 2005). RESULTS: All the patients had a unilateral orbital malignant melanoma. A primary tumour was diagnosed in one case. There was metastatic orbital localisation of a cutaneous malignant melanoma in two cases. In six cases, a secondary melanoma originated from the uveal tract (three cases), conjunctiva (two cases), or paranasal sinuses (one case). All the patients underwent surgical treatment of the tumour (exenteration in 5 cases; subtotal exenteration in one case; subtotal excision in two cases; and craniofacial resection in one case) combined with immunotherapy in one case. The median age at surgery was 66 years, with a mean postoperative follow-up of 17 +/- 14 months. Four patients died of widespread dissemination of the melanoma after a mean time of 13 +/- 7 months. Two more patients died of causes other than melanoma. Three patients were still living at 9, 33 and 45 months after surgery. None of the patients presented with a local relapse of the melanoma during follow-up. CONCLUSION: Although different approaches have been proposed, the prognosis of orbital melanoma remains poor. In our experience too, the patients with longest survival were those whose tumours were exenterated.

Idiopathic retroperitoneal fibrosis: clinicopathologic features and differential diagnosis.

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease often causing obstructive uropathy. We evaluated the clinicopathologic features of 24 patients with IRF to characterize the histopathology of the disease and to provide a framework for the differential diagnosis with other retroperitoneal fibrosing conditions. Retroperitoneal specimens were analyzed by light and electron microscopy and by immunohistochemistry. Most patients presented with abdominal/lumbar pain, constitutional symptoms, and high acute-phase reactants. Overall, 20 had ureteral involvement and 13 developed acute renal failure. The retroperitoneal tissue consisted of a fibrous component and a chronic inflammatory infiltrate with the former characterized by myofibroblasts within a type-I collagen matrix. The infiltrate displayed perivascular and diffuse patterns containing lymphocytes, macrophages, plasma cells, and eosinophils. The perivascular aggregates had a central core of CD20(+) cells and a mantle of CD3(+) cells in equal proportions. In the areas of diffuse infiltrate, CD3(+) cells outnumbered the CD20(+) cells. Most plasma cells were positive for the IgG4 isotype. Small vessel vasculitis was found in the specimens of 11 patients. Our study indicates that a sclerotic background with myofibroblasts associated with a diffuse and perivascular infiltrate mainly consisting of T and B lymphocytes may be a pathological hallmark of IRF.