Tophaceous gout presenting as a dorsal nasal lump

A literature review reveals that gout has been described as affecting many sites in the head and neck region, both in the arthritic and tophaceous form. Gout can often mimic malignancy or infection, and has been described as causing acute airway problems requiring emergency tracheotomy. Here we describe the first published case of tophaceous gout affecting the soft tissues overlying the nasal bones. The patient presented with a bony, hard, dorsal hump and requested aesthetic rhinoplasty. We also describe an endoscopic technique for removal of tophi using a powered microdebrider system with a protected burr head. Endoscopic powered microdebrider blade excision of tophi affecting the limbs has already been described, with reduced complications when compared with conventional curettage and debridement techniques. This is the first such application to the nose.     

Surgical treatment of pharyngostomes in irradiated patients. Our experience with musculocutaneous pectoralis major flap and hyperbaric oxygen therapy

CONCLUSION: Our experience confirms that pectoralis major flap is the first-choice technique for repairing recurrent hypopharyngeal fistulae in previously irradiated patients in whom microsurgical techniques are not indicated, and that hyperbaric oxygen therapy helps to solve this complex pathology. OBJECTIVES: A pharyngostome is a complication encountered when performing surgical operations on pharyngolaryngeal structures. The authors present their experience of treating recurrent complex pharyngostomes in previously irradiated patients in poor physical health. These patients need a simple, safe reconstruction with a low incidence of postoperative complications. MATERIAL AND METHODS: A pedicled pectoralis major flap was used for reconstruction: the skin side of the flap was used to restore the continuity of the pharyngeal mucosa, while the muscle was used to reconstruct the intermediate layer. The skin layer was completed by means of a free skin graft. In all cases, surgical treatment was combined with hyperbaric oxygen therapy before and after the operation. RESULTS: A total of 10 patients, all of whom had previously undergone surgery and radiotherapy, had recurring or pluri-recurring pharyngostomes. All patients (8 males, 2 females; age range 52-80 years) had previously been affected by carcinoma of the pharyngolaryngeal region. All underwent major local Ablation together with radical neck dissection and radiotherapy. In all cases there was mucosa on the posterior wall; a musculocutaneous pectoralis major flap was used in all cases for reconstruction.     

Paroxysmal positional vertigo as a complication of osteotome sinus floor elevation

Paroxysmal positional vertigo (PPV) is a high prevalence, vestibular end organ disorder due to the detachment of the utricular otoconia floating in the posterior or lateral semicircular canal. Even though in the majority of cases the etiology of PPV is unknown, it may follow viral infection, vascular disorders and head trauma after different surgical procedures. The aim of this study was to investigate the correlation between PPV and the surgical trauma induced by the vibratory and percussive forces on the upper maxilla during the osteotome sinus floor elevation procedure. We performed a complete otoneurological examination on 146 patients affected by atrophic ridges before and after upper maxilla surgery. Four patients showed a PPV of the posterior semicircular canal controlateral to the implanted side 1 or 2 days after the surgical procedure, which promptly was solved with the Epley re-positioning maneuver. We hypothesize that the surgical trauma, and specifically the pressure exerted by the osteotomes, determines the detachment of the otoliths from the utricular macula while the patient head position, hyper-extended and tilted opposite to the side where the surgeon is working, favors the entry of these free-floating particles in the posterior semicircular canal of the implanted side. Although this disease is rather frequent in the normal population and it is a benign, self-limiting peripheral disorder, it should be considered by the oral surgeon as a possible complication of pre-prosthetic upper maxilla surgery, and the patient should be informed before undergoing surgery.     

Immunological mechanisms elicited at the tumour site by lymphocyte activation gene-3 (LAG-3) versus IL-12: sharing a common Th1 anti-tumour immune pathway

The experimentally induced TS/A murine mammary carcinoma is poorly immunogenic and mainly infiltrated by antigen-presenting cells (APCs), namely macrophages and immature dendritic cells (DCs). Human (h) and mouse (m) lymphocyte activation gene-3 (LAG-3 or CD233) is a physiological MHC class II ligand and powerful APC activator. A gene transfer approach has revealed its anti-tumour activity in this model: hLAG-3 was more effective than mLAG-3. To obtain a clearer picture of the immunoregulatory mechanisms associated with the rejection dynamics of h- and m-LAG-3 transfectants, immunohistochemistry and confocal microscopy analyses of TS/A-hLAG-3, TS/A-mLAG-3, and control TS/A-pc tumours were performed. The immune events elicited by mLAG-3 and m-interleukin (IL)-12 were also compared, since their rejection kinetics were quite similar, and LAG-3 enables IL-12 production by macrophages and DCs. Both the TS/A-h- and, to a lesser extent, the m-LAG-3 rejection areas were characterized by an impressive recruitment of APCs, granulocytes, NK cells, CD4+ T lymphocytes and CD8+ IFNgamma-expressing cells. In both cases, infiltration by APCs was accompanied by strong CD80 and CD86 expression and macrophage nitric oxide (NO) synthase up-regulation. Distinct expression of IL-12 and CXCL9 was also found, especially in the draining lymph nodes. T lymphocytes and CD86-expressing APCs were significantly prevalent in both the TS/A-h- and the m-LAG-3 compared with the TS/A-mIL-12 rejection area. Production of IFNgamma, TNFalpha and IL1beta, and chemokines, namely CXCL5, CXCL9, CXCL10, CXCL11, CCL5, and CCL2, by infiltrating leukocytes and signs of defective neovascularization were detected in tumours expressing h-LAG-3-, m-LAG-3-, and m-IL-12. However, IFNgamma, CCL2, and CCL5 production prevailed in the TS/A-hLAG-3 rejection area. Taken together, these results indicate that LAG-3 expression by engineered tumour cells efficiently promotes intra-tumoural recruitment, activation, and Th1 commitment of APCs, and leads to a wide intra-tumoural influx of non-specific and specific reactive cells, and the release of immunoregulatory and cytotoxic mediators. Many of LAG-3's anti-tumour activities are shared with IL-12.     

The para substituent of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamides is a major structural determinant of in vivo disposition and activity of selective androgen receptor modulators

Selective androgen receptor modulators (SARMs) have many potential therapeutic applications, including male hypogonadism, osteoporosis, muscle-wasting diseases, sexual libido, and contraception. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamides bearing a four-halogen substituent in the B-ring that displayed in vivo activity were identified in our previous study. Interestingly, in vivo pharmacological activity was not correlated with in vitro androgen receptor (AR) binding affinity. In this study, analysis of the area under the concentration-time curve-response relationship demonstrated that the discrepancy between in vitro and in vivo pharmacological activity of these halogen-substituted SARMs was due to differences in systemic exposure rather than intrinsic pharmacological activity. Studies also suggested that two simple criteria (i.e., Ki < 10 nM and lower in vivo clearance) could be used to identify efficacious and potent SARMs. We tested this hypothesis using a series of four compounds incorporating either a nitro or cyano substituent at the para-position of the A- and B-aromatic rings. The S-3-(4-nitrophenoxy) and S-3-(4-cyanophenoxy) 2-hydroxy-2-methyl-N-(4-nitro-3-trifluromethylphenyl) propionamides (S-19 and S-20, respectively) and S-3-(4-nitrophenoxy) and S-3-(4-cyanophenoxy) 2-hydroxy-2-methyl-N-(4-cyano-3-trifluromethylphenyl) propionamides (S-21 and S-22, respectively) demonstrated high AR binding affinity, with Ki values ranging from 2.0 to 3.8 nM. Pharmacokinetic studies of selected compounds showed that the in vivo clearance of S-22 was the slowest followed sequentially by S-20, S-21, and S-19. The dose-response relationships for S-22 showed that S-22 exerted efficacious and selective activity in anabolic tissues at dose rates as low as 0.03 mg/day, indicative of the high potency of this compound in anabolic tissue (relative potency 4.41) and its potential for clinical use in androgen deficiency-related disorders.     

Analytical assessment of MALDI-TOF Imaging Mass Spectrometry on thin histological samples. An insight in proteome investigation

BACKGROUND: The development of MALDI Imaging Mass Spectrometry is a promising technique in the investigation of biological molecular repertoire. We have pursued an analytical assessment of this technique in its application to proteome analysis. METHODS: A specific statistical method of analysis has been developed to enable data processing in the absence of internal standards, by defining similarity scores. RESULTS: The investigated linear mode MALDI-TOF set-up allows to obtain data variations comprised within the 30% of variation when assaying tissues samples from the same animal, while the 60% of variation was highlighted in the inter-mice series assaying syngenic animals. CONCLUSIONS: This analytical assessment represents the first step of a process that should validate the utilisation of this technique in the clinical practice.