A rare case of hypopharyngeal screw migration after spine stabilization with plating.

Anterior cervical spine fusion and stabilization with plating are well-established surgical procedures for the treatment of myelopathy, cervical spine traumas, and spinal infectious diseases. Various complications have been described in the literature, more frequently, intraoperative bleeding, peri- or postoperative hypopharyngeal, and/or esophageal ruptures with mediastinal deep infection and loosening and extrusion of the screws from the plating. Screw migration has also been observed as a complication of the procedure, either early in the postoperative period or delayed, even after many years. In some instances, the esophageal perforation can recover spontaneously with absence of complications, even if a case of plate failure and graft migration with lethal sudden airways obstruction has been reported. We describe a case of hypopharyngeal screw migration after cervical spine stabilization with plating never described before in the literature.

Pigmented basal cell carcinomas in Gorlin syndrome: two cases with different dermatoscopic patterns.

We describe two nonconsanguineous white patients with multiple pigmented basal cell carcinomas (BCCs) that were histopathologically confirmed. The first patient had calcification of the cerebral falx, multiple keratocysts in the jaw, and other malformations of the cranial and finger bones. The second patient presented with multiple dermoid cysts, calcification of the cerebral falx, keratocysts of the mandible, and agenesis of left kidney. Both patients had palmar pits. Both denied any family history of cutaneous tumours. On dermatoscopic examination of patient 1, multiple, bluish, confluent and large globules were seen. The second patient had blue ovoid globules, arborizing vessels, and areas shaped like maple leaves and spoke-wheels. Based on the clinical and radiological features we diagnosed both patients as having Gorlin syndrome (GS). To our knowledge, there are no previous reports of white patients with GS showing only pigmented BCCs. The dermatoscopic patterns were different in the two patients, and to our knowledge, this is the first report of a patient with GS showing a spoked-wheel dermatoscopic pattern.

Calcipotriol induces apoptosis in psoriatic keratinocytes.

In recent years, vitamin D3 analogues have become one of the most widely prescribed topical treatments for mild or moderate chronic plaque psoriasis. These molecules are effective and safe, but their exact mechanism of action is not completely understood. In vitro studies have shown that D3 analogues decrease proliferation and induce differentiation of keratinocytes, and have strong immunomodulating effects, but there are no conclusive data about apoptosis. The aim of this study was to evaluate differences in apoptotic response between lesional and perilesional keratinocytes of patients with psoriasis before and after treatment with calcipotriol, a synthetic vitamin D3 analogue. Keratinocytes were isolated from psoriatic plaques including lesional and perilesional skin, and cultured. Cells were treated with calcipotriol for 20 h and examined under confocal microscopy after staining with propidium iodide. The number of apoptotic cells after incubation with calcipotriol was significantly higher in lesional than in perilesional keratinocytes (P < 0.05) or non-treated psoriatic keratinocytes (P < 0.05). In conclusion, calcipotriol seems to induce apoptosis in psoriatic keratinocytes.

Correlation between nasal mucociliary clearance time and gastroesophageal reflux disease: our experience on 50 patients.

OBJECTIVES: It is increasingly suggested that gastroesophageal reflux disease (GERD) could play an important role in chronic rhinosinusitis. The aim of our study was to evaluate the nasal mucociliary clearance time in GERD patients and if any correlations could be assumed. METHODS: Fifty GERD patients endoscopically diagnosed underwent an ear, nose and throat evaluation. The saccharin test and the 20-Item Sino-nasal Outcome Test (SNOT-20) were administered to 50 participants who correspond to our inclusion criteria. The saccharin test is a validated proof to verify the nasal mucociliary clearance time and the SNOT-20 is a disease-specific, health-related quality of-life questionnaire widely used for the assessment of rhinosinusitis. RESULTS: Thirty-seven (74%) patients showed a significant increment in their saccharin test values in comparison with the others subjects (23.79+/-5.58 vs 8.15+/-2.06min; P=0.0001). This group of patients reported only typical gastroesophageal symptoms (GES) without any other complaint. Gastroesophageal endoscopic findings revealed some interesting and unexpected results in this subgroup. The remainder of patients considered (13/50; 26%) showed normal values for nasal mucociliary clearance time and they referred only typical extraesophageal symptoms (EES). In any case and in both groups rhinosinusitis complaints were present. The SNOT-20 test results were normal in all patients even if a significant difference for GES group could be highlighted (19.3 vs 7.4; P<0.005). CONCLUSION: This study supports the assumption of possible and important correlations between nasal mucociliary clearance time and GERD. GERD could be an altering factor for nasal function also in absence of laryngo-pharyngeal symptoms although to verify this interesting hypothesis more validated data are necessary.

Variable responses to rituximab treatment in neuromyelitis optica (Devic's disease).

We have described two cases of Devic's disease patients treated with rituximab with different outcomes. The results indicate that there may be early unresponsiveness in very aggressive cases. Well designed clinical trials are needed to assess treatment effects in such a rare disease.

A double buccal fat pad flap for middle palate defect closure--a new technique for palate closure.

In this article a new method of closing palatal defects by means of buccal fat pad flaps is reported. A double buccal fat pad flap in association with Le Fort I osteotomy approach was adopted to remove tumours of the palate and nasal fossae. The technique is described in a case of adenocarcinoma arising from the nasal septum and its indications and advantages are discussed.

Cytomorphologic and ultrastructural study of nasal mucosa by means of brushing: a comparison between asymptomatic and rhinitic subjects.

The authors compared the cytomorphologic and ultrastructural features of nasal epithelium collected by means of brushing from asymptomatic subjects with these of patients affected by nasal polyposis (NP), allergic (AR) and non-allergic rhinitis (NAR). A brushing of nasal epithelium was taken from each member of both groups, and analysed under light and electron microscopy. The observation showed normal ciliary patterns and preserved intercellular joints in the great majority of asymptomatic subjects, while in all subjects of the pathologic group the junctions appeared variously damaged or absents, with ciliary abnormalities. The damage to the intercellular joints, rather than the alterations of ciliary patterns, seemed to represent in this study the border between the absence of symptoms and the presence of chronic inflammation. Therefore, a reduced tightness of the intercellular joints could contribute to the impairment of the mucociliary clearance, priming the vicious circle that leads to the condition of chronic inflammation.

Self-expandable metal stents in the management of cervical oesophageal and/or hypopharyngeal strictures.

AIM: To assess the usefulness of self-expandable metal stents in the recanalization of cervical and/or hypopharyngeal strictures. MATERIALS AND METHODS: We report our experience in 10 patients with inoperable cervical and/or hypopharyngeal strictures treated by implantation of 11 uncovered self-expandable metal stents inserted perorally under fluoroscopic guidance. The stent was placed in the hypopharynx and cervical oesophagus in 3 patients and cervical oesophagus alone in 7. There were 8 men and 2 women, mean age 70.2 years, range 45-85 years. All patients but two had malignant stricture caused by squamous cell carcinoma, in one case there was a benign postoperative stenosis secondary to laryngectomy, and in the last patient a local recurrence from thyroid cancer. RESULTS: Eleven stents were placed in 10 patients: technical success was achieved in 9 cases while clinical improvement was obtained in 8 cases. Seven of ten patients had a rapid improvement of dysphagia. One patient had a distal misplacement of the prosthesis, while in the other two cases stent position was very proximal and interfered with swallowing. A mean 9-month follow-up was obtained (range 3-24 months). Four patients with malignant stricture developed proliferation of neoplastic tissue after 2-5 months. The only patient treated for a benign stricture developed inside proliferation of granulation tissue after 4 months. CONCLUSION: Despite several technical difficulties and a high rate of late complications, recanalization of cervical oesophageal strictures by self-expandable metal stents allowed good palliation of symptoms. Stents proved to be effective and well tolerated palliative treatment also for hypopharyngeal stenoses.

Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival.

Adhesion of human primary skin fibroblasts and ECV304 endothelial cells to immobilized matrix proteins, beta1 or alphav integrin antibodies stimulates tyrosine phosphorylation of the epidermal growth factor (EGF) receptor. This tyrosine phosphorylation is transiently induced, reaching maximal levels 30 min after adhesion, and it occurs in the absence of receptor ligands. Similar results were observed with EGF receptor-transfected NIH-3T3 cells. Use of a kinase-negative EGF receptor mutant demonstrates that the integrin-stimulated tyrosine phosphorylation is due to activation of the receptor's intrinsic kinase activity. Integrin-mediated EGF receptor activation leads to Erk-1/MAP kinase induction, as shown by treatment with the specific inhibitor tyrphostin AG1478 and by expression of a dominant-negative EGF receptor mutant. EGF receptor and Erk-1/MAP kinase activation by integrins does not lead per se to cell proliferation, but is important for entry into S phase in response to EGF or serum. EGF receptor activation is also required for extracellular matrix-mediated cell survival. Adhesion-dependent MAP kinase activation and survival are regulated through EGF receptor activation in cells expressing this molecule above a threshold level (5x10(3) receptors per cell). These results demonstrate that integrin-dependent EGF receptor activation is a novel signaling mechanism involved in cell survival and proliferation in response to extracellular matrix.

Computerised tomography evaluation of the frontal recess in inflammatory diseases of the frontal sinus: standardisation of a new technique.

The authors present a new investigation technique by means of CT of the frontal sinus drainage pathway, the frontal recess, which could be of considerable help in defining its potential role in determining a chronic or recurrent inflammatory process of this cavity. Among the main characteristics of this technique are: (1) a clear presentation of the course and conformation of the recess and its relations with surrounding structures; (2) speedy, and therefore economical, operation (12 min for a complete examination); and (3) tolerability, because this examination starts off with axial-scans, which, compared to CT coronal projections and MRI scans, are less prone to defects and do not require strained postures. This this means that all kinds of patients can be assessed, which is a basic requirement for achieving standardisation. With axial scans the authors work from paraxial reconstructions (oblique sagittal) which, in their opinion, give the best definition of the frontal recess so far recorded.

Soluble integrin ligands and growth factors independently rescue neuroblastoma cells from apoptosis under nonadherent conditions.

We have investigated the role of extracellular matrix (ECM) and growth factors in the survival of nonadherent human neuroblastoma cells (line SK-N-BE). Cells cultured in serum-free medium under nonadherent conditions died with apoptotic-like features (chromatin condensation and nuclear fragmentation). SK-N-BE cells underwent neuronal differentiation in response to retinoic acid (RA). While RA itself did not induce apoptosis, differentiation increased the susceptibility of SK-N-BE cells to detachment-induced apoptosis. The appearance of the apoptotic-like phenotype required the maintenance in suspension of SK-N-BE cells for at least 16 h (12.43 +/- 1.40% of cells undergoing apoptosis) and the percentage increased up to 46.84 +/- 3.15% after 24 h. Suspension-induced apoptosis did not depend on increased intracellular Ca2+ levels nor on de novo protein synthesis and was not associated with extensive DNA degradation. Stimulation by soluble collagen I rescued suspended cells from apoptosis, even in the absence of cell adhesion and spreading. The survival promoting effect of ECM was mediated by the integrin receptors, since (1) the protective effect of soluble collagen I was blocked by anti-integrin antibodies to beta 1 and alpha 1 subunits and (2) the antibody-induced clustering of alpha 1, alpha 3, alpha v, beta 1, and beta 3 integrins rescued SK-N-BE cells cultured in suspension from apoptosis. As expected, adhesion on immobilized ECM proteins, collagen I, or laminin (0.1 to 10 micrograms/ml) also rescued SK-N-BE cells from apoptosis in a dose-dependent manner. The de novo protein synthesis was required to promote the survival effect of ECM, since cycloheximide completely abolished the protective effect of collagen I and protection from apoptosis by ECM or by anti-beta 1 antibody was associated with the increased expression of bcl-2. In addition to integrin stimulation, serum, insulin, and nerve growth factor inhibited suspension-induced apoptosis of SK-N-BE cells. The survival effect of serum and growth factors did not require the synthesis of new proteins, unlike the ECM effect. These data show that matrix proteins can promote cell survival in neuronal cells via integrin receptors. This effect does not require cell adhesion and the subsequent changes in cell shape as it can be mediated by soluble integrin ligands in suspended cells and involves a signaling pathway different from that triggered by growth factors.

[The evolution of the techniques used to correct nasal septum function]. / La evoluzione delle tecniche di correzione funzionale del setto nasale.

At the dawn of rhinosurgery, the otolaryngologist operated on the nasal septum while a plastic surgeon handled treatment of the "noble" portion of the nose, i.e. the nasal pyramid. However, the plastic surgeon dealt more with esthetics than with function. Discussion and doubts revolved around the priorities of septum vs. pyramid treatment. Such doubts have often gone unresolved and has led to an unusual dichotomy in nasal surgery: the break down into septoplasty and rhinoplasty. This scission has fallen by the wayside during the course of the years. Indeed, today, where necessary, one tends associate corrective rhinoplasty during the course of septal procedures. During this historical review of functional surgery of the nasal septum, some mention is made of the numerous techniques and variations thereof which have been presented by various authors.

[Coronal CT in the indication of the endoscopic surgery of the sinus]. / La T.C. coronale nelle indicazioni alla chirurgia endoscopica sinusale.

In this paper the Authors affirm that Functional Endoscopic Sinus Surgery is the technique of choice for treatment of nonneoplastic pathologies of paranasal sinuses, particularly in chronic infective and polypoid sinusitis. Furthermore, they confirm CT scans are mandatory in preoperative planning in order to delineate precisely the structures surrounding the surgical field (the lamina papyracea and possible dehiscences, the brain, the lacrimal duct, the internal carotid artery and the optic nerve), and thereby avoid any possible damage during surgery. If endoscopic examination and clinical history suggest a massive involvement of ethmoid cavities, both axial and coronal CT scans are necessary. Inasmuch as the crucial point in the development of chronic sinus pathology is the ostio-meatal complex, the Authors indicate that this structure can be clearly identified and studied by means of coronal CT scans, since in this case it is not necessary to clarify the depth of the nasal fossae, but, instead, to reveal the exact situation and configuration of the two fundamental lamellae, the uncinate process and the bulla. These structures lie on a vertical plane and cannot be studied with axial CT scans without reviewing several series scans made in close proximity, which increases the patient's exposure to x-rays as well as the expense of the study. This paper is an attempt to shorten and rationalize routine radiologic procedures when a limited ethmoid involvement, previously detected by careful endoscopic examination, is under investigation.

Role of tyrosine phosphorylation in matrix-induced neurite outgrowth in human neuroblastoma cells.

Adhesion of human neuroblastoma cells (SK-N-SH clone SY5Y) to laminin or collagen type IV promotes tyrosine phosphorylation of a group of proteins with molecular mass ranging from 100 to 130 kDa and of a protein of 180 kDa. The same pattern of tyrosine phosphorylation was observed when SY5Y cells were allowed to adhere to culture dishes coated with monoclonal antibodies directed to the integrin subunits expressed in the cells, alpha 1, alpha 3, and beta 1, indicating that these receptors are responsible for this signaling mechanism. Using specific antibodies we identified the focal adhesion kinase p125FAK as a component of the 100- to 130-kDa phosphoproteins. Treatment with genistein or herbimycin A, two specific tyrosine kinase inhibitors, greatly reduced the tyrosine phosphorylation of the 100- to 130- and the 180-kDa proteins in response to laminin or collagen IV. Concomitantly, neurite outgrowth on the matrix proteins was strongly inhibited. This effect was observed in two distinct neuroblastoma cell lines, SY5Y and SK-N-BE. Genistein and herbimycin A treatment did not affect cell viability nor cause retraction of preformed neurites. These data suggest that matrix-induced tyrosine phosphorylation events are involved in neurite extension.

Integrin-mediated signal transduction in human endothelial cells: analysis of tyrosine phosphorylation events.

Adhesion of human umbilical endothelial cells to fibronectin resulted in increased tyrosine phosphorylation of a group of proteins with molecular mass ranging from 100 to 130 kDa and of a 70 kDa protein. This pattern of tyrosine phosphorylation was also observed when endothelial cells adhered to vitronectin, collagen IV, collagen I and laminin or to culture dishes coated with antibodies directed to either beta 1, alpha 3, alpha 5, alpha 6 or beta 3 integrin subunits. Increased phosphorylation of the 100-130 kDa proteins was detectable as early as 30 sec after adhesion, reached maximal level after 15 min, and remained high as long as the cells adhere to culture dishes. The 70 kDa protein was phosphorylated with a slower kinetics and its phosphorylation increased over a period of 3 h. Using specific monoclonal antibodies, the major component of the 100-130 kDa complex was identified as the focal adhesion tyrosine kinase p125FAK. The phosphorylation of the p125FAK was also observed by inducing beta 1 integrin clustering in non adherent HEC, indicating that this is a primary signalling event induced by integrins. Using tyrosine kinase inhibitors, we show a direct correlation between integrin-stimulated tyrosine kinases and assembly of focal adhesions and actin fibres.

Transnasal sinusectomy with combined microscopic and endoscopic technique.

Severe, diffuse polyposis can be adequately treated through a transnasal approach which combines microscopic and endoscopic surgery. The operating microscope is used to perform ethmoidectomy, usually from the front to the back, and to open the sphenoid sinus and the antral window. The telescopes allow the sphenoid and maxillary sinuses to be cleaned under direct view control as well as enabling good drainage to be performed from the frontal sinuses. The results from 22 consecutive patients were good, with a very low rate of minor post-operative complications.

Insulin supplement in type 2 diabetic patients with secondary failure to oral agents ameliorates hepatic and peripheral insulin sensitivity but not insulin secretion.

In order to investigate the mechanism of amelioration of metabolic abnormalities with supplementary doses of insulin, islet B-cell function and insulin sensitivity were measured in 10 patients with Type 2 diabetes in secondary failure to oral agents. A small dose of ultralente insulin (0.26 +/- 0.07 U kg-ideal-body-weight-1) was added in the morning before breakfast. After 3 months insulin therapy and progressive improvement of metabolic control (HbA1 from 10.5 +/- 0.4 to 9.0 +/- 0.3% at the end of insulin treatment, p less than 0.001), basal C-peptide and incremental area during an oral glucose tolerance test were unchanged. In vivo peripheral insulin sensitivity (euglycaemic clamp with insulin infusion of 40, 160, and 600 mU m-2 min-1, respectively) was significantly improved (glucose requirement: to 4.7 +/- 1.0 from 3.0 +/- 0.6 mg kg-1 min-1, p less than 0.05 at first insulin level; to 10.8 +/- 0.5 from 9.3 +/- 0.7 mg kg-1 min-1, p less than 0.01 at second level; to 13.3 +/- 0.6 from 11.8 +/- 0.8 mg kg-1 min-1, p less than 0.025 at third level). Basal hepatic glucose production was also significantly reduced (from 4.3 +/- 0.4 to 3.3 +/- 0.3 mg kg-1 min-1, p less than 0.05), and residual glucose production further suppressed after insulin supplement (from 1.1 +/- 0.4 to 0.3 +/- 0.2 mg kg-1 min-1 after 120 min at 100 mU l-1 plasma insulin, p less than 0.05). Specific insulin binding to mononuclear leucocytes was unchanged (from 3.1 +/- 0.3 to 3.5 +/- 0.3%, NS).

Lymphocyte Na,K-ATPase is reduced in aged people.

Na,K-ATPase-dependent 86Rb uptake, maximum velocity (Vmax), Michaelis constant (Km) of the uptake, and [3H]-ouabain binding were investigated in the lymphocytes of 10 elderly subjects (age greater than 60 years), and in 10 middle-aged (41 to 60 years) and 10 young controls (age less than or equal to 40 years). 86Rb uptake was reduced in elderly versus both middle-aged and young subjects (20.14 +/- 3.30 v 35.60 +/- 2.67, P = .002, and v 36.53 +/- 4.49 nmol, P = .012), as was the number of [3H]-ouabain binding sites per cell (32,662 +/- 2,215 v 40,420 +/- 1,184, P = .011, and v 40,596 +/- 1,349, P = .014). Vmax was reduced in elderly v young subjects (1.20 +/- 0.10 v 1.64 +/- 0.13, P = .034), but not versus the middle-age group (1.20 +/- 0.10 v 1.54 +/- 0.12 nmol.min-1, NS). Km was no different among the three groups. No differences were found between middle-aged and young subjects. Significant correlations were observed between age and Na,K-ATPase-dependent 86Rb uptake (r = -.620, P = .00009), Vmax (r = -.439, P = .024), and [3H]-ouabain binding sites (r = -.648, P = .002). Moreover, the site number was positively correlated with both uptake (r = .635, P = .002) and Vmax (r = .554, P = .011). These differences were observed both in women and men. We conclude that there is an age-dependent reduction in lymphocyte Na,K-ATPase activity, which is fully manifested over 60 years, and that this alteration is probably due to the reduced number of functional units of Na,K-ATPase in advancing age.

[Insulin response to food in obese women]. / Risposta insulinica al pasto in donne obese.

The effects of two standard meals (meal A: 20 g proteins, 20 g lipids, 80 g maltodextrin; meal B: meal A plus 52 g lipids) on insulin and C-peptide secretion and on plasma levels of glucose and free fatty acids (FFA) was studied in 12 obese women separated into two groups according to the onset of obesity. One group (n = 6) developed into obesity after puberty (OP), the other (n = 6) became obese after pregnancy (OG). Meals A.--In OP women, the maximum insulin response was reached at 30 min after meal (141.8 +/- 14.2 microU/ml) and insulinaemia fell to the basal values at 180 min; in OG women the insulin response was linear in the interval 30-150 min after meal. The maximum secretion of C-peptide occurred between 30 min and 90 min in OP and between 60 min and 120 min in OG; the secretion rate was similar in the two groups. Blood glucose levels returned to the basal values at 120 min after meal in OP and at 180 min in OG. FFA levels significantly decreased after meal in both groups (p less than 0.01 vs basal values). Meal B.--Insulin secretion was decreased at 30 min after meal in OP and at 150 min in OG and the levels of C-peptide was not modified in both groups. The glycaemic response was unchanged in OP, but was lower in OG women (p less than 0.02). These results show that OP women present stronger and more rapid insulin response to meals than the OG women; this conclusion is supported by the analysis of the secretion of C-peptide. Blood glucose levels return to basal values faster in OP than in OG women. The blood level of FFA after the standard meals A and B are normal both in OP and OG women.