Increased risk of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a three-year longitudinal study with phalangeal QUS measurements.

Type 2 diabetes mellitus (T2DM) is associated with a higher risk of fractures even in presence of normal or increased bone mineral density. The purpose of this three-year longitudinal study was to evaluate the risk of osteoporotic fractures by assessing the changes of Quantitative Ultrasound (QUS) parameters in a group of postmenopausal women with type 2 diabetes mellitus (T2DM) compared with non-diabetic controls. The measurements were taken on a group of 18 postmenopausal women affected by T2DM and 18 healthy age-matched controls, aged 55-70 years, referring to the Osteolab laboratory at the ISBEM Research Institute (Brindisi, Italy) between 2009 and 2013. Subjects had baseline and 3-year follow-up measurements with phalangeal QUS carried out by a DBM Sonic Bone Profiler 1200 (Igea®); medical history, current drug therapies and risk factors for fractures were recorded for each patient. The analyzed phalangeal QUS parameters were Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), Fast Wave Amplitude (FWA) and Signal Dynamic (SDy). At the baseline visit we found no statistically significant difference between T2DM and non-diabetic patients when looking at phalangeal QUS parameters. At the three-year follow-up visit, a significantly higher decrease of both BTT (P<0.001) and AD-SoS (P<0.001) parameters was found in the T2DM group. On the contrary, the decrease of FWA was significantly higher in non-diabetic controls (P<0.001). Our data confirm the ability of phalangeal QUS to detect differences in the risk of osteoporotic fractures in T2DM postmenopausal women compared to non-diabetic controls. The study suggests that T2DM women present a higher cortical porosity and increased trabecular bone density compared to non-diabetic controls, respectively shown by the higher decrease of both AD-SoS and BTT and the lower decrease of FWA.

Alendronate: new formulations of an old and effective drug to improve adherence avoiding upper gastrointestinal side effects.

OBJECTIVE: Alendronate is a second generation bisphosphonate which has been widely used in medical practice for two decades to treat osteoporosis and prevent fragility fractures both in elderly people and in younger patients. METHODS: Since many papers have been recently published and new formulations or dosages have been developed, our aim was to review the most significant medical literature addressing the issues of efficacy, safety, posology and formulations of the treatment with alendronate in osteoporotic patients. RESULTS: The efficacy of alendronate in reducing the risk of vertebral and non-vertebral fractures has been demonstrated in several studies. Despite favourable data coming from clinical trials, tolerability of alendronate represented a critical issue since its introduction into real clinical practice, possibly leading to early discontinuation of the therapy, especially when combined with lack of motivation of the patient. For this reason, new dosages and formulations of alendronate have been developed, alone or in combination with vitamin D, which have shown to reduce the impact of gastro-oesophageal adverse events, and minimize discomfort due to the need of adopting unfavourable postural positions every day, fasting for at least one hour. CONCLUSIONS: Alendronate is the most frequently used antifracture therapy among those currently available. The increasing use of the 70 mg weekly dosages and newest formulations of this drug are expected to reduce adverse events and increase adherence to the antifracture therapy, thus resulting in better clinical outcomes when treating osteoporotic patients.

Socioeconomic burden of total joint arthroplasty for symptomatic hip and knee osteoarthritis in the Italian population: a 5-year analysis based on hospitalization records.

OBJECTIVE: To assess the burden of total joint arthroplasties (TJAs) performed for symptomatic hip and knee osteoarthritis (OA) in the Italian population. METHODS: We analyzed national hospitalizations and diagnosis-related group databases to compute incidence, annual percent change (APC), direct costs, and working days lost between 2001 and 2005 following TJA due to OA. RESULTS: In 2005, we recorded a total of 41,816 (APC +5.4; 95% confidence interval [95% CI] 5.1-5.8) and 44,051 (APC +13.4; 95% CI 13.1-13.8) hip and knee arthroplasties, respectively. Women represented the majority of patients undergoing TJA procedures (female:male ratio 1.7:1 for hip arthroplasties and 2.9:1 for knee arthroplasties). When analyzing the data by age groups, most of the patients were in the age groups 65-74 years and ≥75 years, although the highest increases were observed in those ages <65 years. Revisions accounted for 6,387 (APC +4.9; 95% CI 4.0-5.7) and 2,295 (APC +17.4; 95% CI 15.7-19.2) procedures for the hip and knee, respectively. Loss of working days in patients ages <65 years was estimated between 805,000 and 1 million days. Hospital costs increased from 741 million to 1 billion euros over the 5-year period (from 412 to 538 million euros for hip arthroplasties and from 329 to 517 million euros for knee arthroplasties). Rehabilitation costs increased from 228 to 322 million euros. Postoperative complications were estimated between 3.1 and 4.4 million euros. The average costs per patient were 16,835 and 15,358 euros for hip and knee arthroplasties, respectively. CONCLUSION: The socioeconomic burden of TJAs performed for symptomatic OA in Italy is remarkable and calls for the adoption of proper preventive measures.

Spindle cell lipoma of the hypopharynx.

Larynx and hypopharynx lipomas are reported to account for approximately 0.6% of benign laryngeal neoplasms. Spindle cell lipoma is a histologically distinct variant characterized by mature adipocytes mixed with collagen-forming spindle cells; only one case of spindle cell lipoma of the larynx has been previously reported. We here describe a new case of spindle cell lipoma of the pyriform sinus successfully treated by means of endoscopic surgical excision. A 77-year-old woman with a 40-year history of dysphagia reported that the condition had markedly worsened over the three years before she came to us. She had difficulty swallowing even semisolid food and she experienced occasional nasal regurgitation of liquid or solid food. Flexible videolaryngoscopy showed a very large mass, covered by normal mucosa that almost totally occupied the right pyriform sinus and was apparently attached to the right arytenoid. Functional endoscopic study and videofluoroscopy of swallowing showed that the bolus progressed exclusively in the left pyriform sinus, with postdeglutitory pooling in the right pyriform sinus and a reflux toward the valleculae during consecutive deglutitions. Computed tomography demonstrated that the hypopharyngeal mass had low attenuation values and negative densitometry. The entire mass was surgically removed during suspension microlaryngoscopy. The histological sections showed mature adipocytes mixed with small and slender spindle cells. Postoperative endoscopic and videofluorosocpic deglutition studies revealed the recovery of normal swallowing. This case indicates that hypopharyngeal lipomas should be included in the differential diagnosis of slowly occurring swallowing impairments.

Bilateral laryngeal pseudoparalysis in xanthoma disseminatum treated by endoscopic laser medial arytenoidectomy.

Xanthoma disseminatum is a rare non-Langerhans' cell histiocytosis, characterized by papular cutaneous eruption, possible mucosal involvement, and frequent association with vasopressin-sensitive diabetes insipidus. Herein we report a case of xanthoma disseminatum with pharyngolaryngeal involvement. In this patient, mucosal xanthomas involving the arytenoid cartilages and the interarytenoid area resulted in laryngeal stenosis and severe impairment of both cricoarytenoid joints' motility. Endoscopic CO2 laser medial arytenoidectomy, according to the technique described by Crumley (1993), and vaporization of interarytenoid xanthomas were successfully performed, thus reestablishing bilateral cordal motility and the laryngeal airway. Four years later, a CO2 laser revision was necessary because of recurrence of xanthomas in the posterior larynx. Two years after the latter operation, the patient has no signs of laryngeal obstruction and has a normal voice quality. This case report suggests that endoscopic medial arytenoidectomy may be successfully used in the treatment of bilateral laryngeal pseudoparalysis secondary to xanthoma disseminatum.

Clinical experience with the treatment of T1b glottic cancer by means of horizontal glottectomy.

This study describes the oncological and functional results of horizontal glottectomy performed in a series of 37 similar patients with T1b glottic cancers. The 5-year overall and disease-free survival rates were, respectively, 85.4% and 91.0%. Decannulation was always possible within a mean period of 16.2 days, and no patient developed laryngeal stenosis. A bypass naso-gastric tube was removed a mean 4.9 days after surgery, and adequate swallowing was soon obtained. The mean duration of post-operative hospitalization was 16 days and no major post-operative complications were observed. Satisfactory vocal function was obtained in all cases. On the basis of these results, horizontal glottectomy was found to be a reliable and safe procedure for the management of T1b glottic cancer.

Cytokines and adhesion molecules in middle ear cholesteatoma. A role in epithelial growth?

The immune response is thought to play a role in dysregulating epithelial growth in cholesteatoma of the middle ear. Through immunohistochemistry (using 18 monoclonal antibodies) on 10 specimens from human middle ear cholesteatomas, T-helper cells mixed with plasma cells, macrophages and scattered T-suppressor and B cells, have been detected in the perimatrix. Mast cells have also been identified in the perimatrix, usually close to the epithelium. Elements positive for D-related human leukocyte antigens (HLA-DR) were more than half of the immune cells. The endothelium of the perimatrix showed a sharp reactivity to the intercellular adhesion molecule-1 (ICAM1) and to the endothelial derived leukocyte adhesion molecule-1 (ELAM1), which play a role in recluting inflammatory cells and modulating the immune response. The expression of ICAM1 in the basal layer of the matrix indicates the homing of inflammatory reactions at the epithelial-stromal junction of the cholesteatoma. An intense expression of interferon-gamma receptor (IFN gamma R) was found in the basal layers of the cholesteatoma matrix, and overexpression of the epithelial growth factor receptor (EGFR) was found in all layers of the matrix. These data support the hypothesis that the epithelial cells in middle ear cholesteatoma are in an activated state and that their hyperproliferation is mediated through cytokines and adhesion molecules.

Characterization of glycated proteins by 13C NMR spectroscopy. Identification of specific sites of protein modification by glucose.

13C NMR spectroscopy has been used to characterize Amadori (ketoamine) adducts formed by reaction of [2-13C]glucose with free amino groups of protein. The spectra of glycated proteins were acquired in phosphate buffer at pH 7.4 and were interpreted by reference to the spectra of model compounds, N alpha-formyl-N epsilon-fructose-lysine and glycated poly-L-lysine (GlcPLL). The anomeric carbon region of the spectrum (approximately 90-105 ppm) of glycated cytochrome c was superimposable on that of N alpha-formyl-N epsilon-fructose-lysine, and contained three peaks characteristic of the alpha- and beta-furanose and beta-pyranose anomers of Amadori adducts to peripheral lysine residues on protein (pK alpha approximately 10.5). The spectrum of GlcPLL yielded six anomeric carbon resonances; the second set of three was displaced about 2 ppm to lower shielding of the first and was assigned to the Amadori adduct at the alpha-amino terminus (pK alpha approximately 7.5). The spectrum of glycated RNase was similar to that of GlcPLL, but contained a third set of three signals attributable to modification of active site lysine 41 (pK alpha approximately 8.8). The assignments for RNase were confirmed by analysis of spectra taken at pH 4 and under denaturing conditions. The spectrum of glycated hemoglobin was comparable to that of GlcPLL, and distinct resonances could be assigned to Amadori adducts at amino-terminal valine and intrachain N epsilon-lysine residues. Chemical analyses were performed to measure the relative extent of alpha- and epsilon-amino group modification in the glycated macromolecules, and the results were compared with estimates based on integration of the NMR spectra.

13C NMR investigation of nonenzymatic glucosylation of protein. Model studies using RNase A.

Nonenzymatic glucosylation of protein is initiated by the reversible condensation of glucose in its open chain form with the amino groups on the protein. The initial product is an aldimine (Schiff base) which cyclizes to the glycosylamine derivative. The aldimine can undergo a slow Amadori rearrangement to yield the relatively stable ketoamine adduct which is structurally analogous to fructose. 13C NMR has been used to characterize these early products of nonenzymatic glucosylation, using RNase A as a model protein. C-1 of the beta-pyranose anomer of the glycosylamine was identified at 88.8 ppm in the spectrum of RNase glucosylated approximately 1:1 with D-[1-13C]glucose. C-1 of the Amadori product was also apparent in this spectrum, resonating as a pair of intense peaks at 52.7 and 53.1 ppm. The anomeric (C-2) resonances of the Amadori adduct were seen in the spectrum of RNase glucosylated approximately 1:1 with [U-13C]glucose. This spectrum was interpreted by comparison to the spectra of reference compounds: D-fructose, fructose-glycine, N alpha-formyl-N epsilon-fructose-lysine, and glucosylated poly-L-lysine. In the protein spectrum, the most intense of the C-2 resonances was that of the beta-fructopyranose anomer at 95.8 ppm. The alpha- and beta-fructofuranose anomers were also observed at 101.7 and 99.2 ppm, respectively. One unidentified signal in the anomeric region was observed in the spectra of poly-L-lysine and RNase, both glucosylated with [U-13C]glucose; no comparable resonances were observed in the spectra of the model compounds.