Use of intralesional cidofovir in the recurrent respiratory papillomatosis: a review of the literature.

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is characterized by exophytic, benign, and papillary lesions infected by the virus in the epithelium of the upper aerodigestive tract. RRP is caused by persistent infection of the respiratory epithelium by human papillomavirus (HPV) HPV6 and-11. The clinical course of RRP is unpredictable, frequently relapsing, and may be lifelong. The aim of this study is to evaluate the efficacy and safety of the use of intralesional Cidofovir in the treatment of RRP. PATIENTS AND METHODS: We have selected articles on the use of cidofovir as adjuvant therapy in laryngeal papillomatosis. We reviewed 20 reports that enrolled 185 patients with "adult onset recurrent respiratory papillomatosis" (AORRP) and 85 patients with "juvenile onset recurrent respiratory papillomatosis" (JORRP). We evaluated concentration of cidofovir, number of injections, injection interval, therapeutic response, side effects, and progression to dysplasia. RESULTS: The mean concentration of cidofovir was 7.5 mg/ml at injection. The mean number of injections per patient is 6 with 26 days between injections. The percentage of patients with dysplasia after use of cidofovir is 1.48%. The AORRP response to cidofovir is better with a 74% complete response rate, compared to 56.5% of the JORRP. CONCLUSIONS: Intralesion use of cidofovir has a good adjuvant action in RRP increasing the complete remission of the disease. The treatment does not increase the risk of laryngeal dysplasia.

Nasal function before and after rapid maxillary expansion in children: A randomized, prospective, controlled study.

OBJECTIVES: Children can well detect and respond to odours in order to have information about food and environment. Rapid Maxillary Expansion seems to improve dental and skeletal crossbite and increase nasal patency correcting oral respiration in children. A previous pilot study suggested that Rapid Maxillary Expansion may lead to improved N-Butanol olfactory thresholds, and peak nasal inspiratory flow values (PNIF). The aim of the present study was to prospectively evaluate olfactory threshold, nasal flows and nasal resistances in children aged from 6 to 11 years before and after Rapid Maxillary Expansion, comparing treated children with a control group of similar age, growth stage (prepubertal) and transversal skeletal deficiency. METHODS: N-butanol olfactory thresholds, anterior active rhinomanometry (AAR) and PNIF were measured in 11 children (6-11 years) before (T0), immediately and 6 months after Rapid Maxillary Expansion application (T1 and T2 respectively), and in a control group of 11 children (6-11 years) whose members remained under observation for the period of the study. RESULTS: Considering the study group, PNIF values improved at T1 respect to the T0 values (p = 0.003), while T2 values were significantly higher than T0 ones (p = 0.0002). N-Butanol Olfactory Threshold significantly improved at each control (p = 0.01, p = 0,01 and p = 0.0003, for T1 vs T0, T2 vs T1, T2 vs T0 respectively). No differences on AAR values were found during the six months follow-up in this group. Considering the control group, no significant differences were found for any of the considered variables during the time of the study. Comparing the two groups, there was a significant increase of PNIF values in the study group compared to the control group (p = 0.003) at T1, which was even more evident six months after Rapid Maxillary Expansion (p = 0.0005). This improvement was not shown by AAR values. N-Butanol Olfactory Threshold showed a significant improvement at T2 respect to T1 (p = 0.002) and T0 (p = 0.0005). CONCLUSION: Rapid Maxillary Expansion seems to significantly improve the respiratory capacity of treated patients, at least in terms of PNIF, and their olfactory function, measured by N-Butanol Olfactory Threshold Test. Further studies should be performed to evaluate if also changes in nasal resistances, measured by AAR, could occur, maybe considering a larger group of subjects and possibly using 4-phase rhinomanometry in order to evaluate the effective resistances during the entire breath.

Mandibular advancement devices vs nasal-continuous positive airway pressure in the treatment of obstructive sleep apnoea. Systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common disorder that may affect at least 2 to 4% of the adult population. Nasal-Continuous Positive Airway Pressure (N-CPAP) is today considered the gold standard for the treatment of OSA. The development of oral appliances (OAs) represents a new approach for the management of this pathology. The aim of this systematic review is to compare the efficacy of OAs and N-CPAP in the treatment of patients with mild to severe OSA. MATERIAL AND METHODS: A PubMed-MEDLINE and Cochrane databases search of articles published between 1982 and 2016 comparing the effect of N-CPAP and OAs in OSA patients was conducted during July 2016. The studies were selected and stratified according to PRISMA and SORT criteria. The main outcome measure was post-treatment Apnoea-Hypopnoea Index (AHI) while secondary outcomes included post-treatment Epworth Score Scale (ESS) score and lowest Oxygen Saturation level. RESULTS: N-CPAP was significantly more effective in suppressing AHI than OA. Moreover, N- CPAP was significantly more effective in increasing post-treatment lowest Oxygen Saturation level than OA. However, no significant different in decreasing ESS values was found between the two treatments. CONCLUSIONS: On the basis of evidence in this review it would appear appropriate to offer OA therapy to those who are unwilling or unable to persist with CPAP therapy. N-CPAP still must be considered the gold standard treatment for OSA and, therefore, OAs may be included in the list of alternative options.

Expression of P53 and isoforms in bening and malignant lesions of the head and neck.

BACKGROUND: P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. METHODS: By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). RESULTS: In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. CONCLUSIONS: We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.

The role of cVEMPs and vHIT in the evaluation of otosclerosis and its eventual vestibular impairment: preliminary findings.

The role of cVEMPs and vHIT in the evaluation of otosclerosis and its eventual vestibular impairment: preliminary findings. OBJECTIVES: Otosclerosis is one of the most common causes of hearing loss in adults, with a prevalence of 0.3% to 0.4% in Caucasians. Vestibular symptoms may occur, with an incidence ranging between 5% and 57% of patients. The aim of our study is to evaluate the vestibular function and its eventual changes after stapes surgery in patients affected by otosclerosis. METHODS: Prospective case-control study. Twenty patients (17 females; age range 33-58; mean age 44) who underwent surgery for otosclerotic disease between April 2012 and February 2014 were prospectively studied. These patients underwent preoperative and postoperative audiological tests. Furthermore, vestibular function was evaluated using the cervical evoked myogenic potentials test (cVEMPs) and video head impulse test (vHIT), preoperatively and postoperatively. A case-control study was also performed. Quantitative and statistical analysis of patients' vestibular function was carried out both before and after stapes surgery. RESULTS: The means of the vHIT gains in the case group were 1.03 on the right side and 1.01 on the left side. A significant difference between case and control groups was seen, with a lower left gain registered in the control group. No cases with a gain of less than 0.8 were found in either group. Moreover, a significant postoperative reduction in P1/NI amplitude was seen in patients complaining of postoperative dizziness or vertigo. CONCLUSIONS: These findings indicate a probable traumatic saccular impairment in patients with vestibular symptoms. However, a longer follow-up may help in understanding the behaviour of cVEMPs in post-stapes surgery vertigo.

Olfactory event-related potentials: a new approach for the evaluation of olfaction in nasopharyngeal carcinoma patients treated with chemo-radiotherapy.

OBJECTIVE: Olfactory dysfunction is a possible side effect of chemo-radiotherapy performed in patients affected by nasopharyngeal carcinoma. Self-rating measurements and olfactory event-related potentials were used and compared in order to evaluate the impact of this treatment on the olfactory system. METHODS: Nine patients underwent subjective evaluation of olfactory function (using visual analogue scales for olfactory symptoms and quality of life, and a six-item Hyposmia Rating Scale), and a quantitative and objective measurement (olfactory event-related potentials). RESULTS: Spearman's rank correlation analyses highlighted significant relationships between the clinical scales and olfactory event-related potentials. Inter-group analyses showed significant differences in the latency and in the amplitude of olfactory event-related potentials between patients and controls. CONCLUSION: Taking into account the small sample size and the lack of pre-treatment assessment, olfactory event-related potentials seemed to allow a more objective diagnosis of unilateral and bilateral olfactory loss. Moreover, olfactory event-related potentials and subjective scales results were concordant.

Subannular T-tubes for the treatment of adhesive otitis: how we do it.

Subannular T-tubes for the treatment of adhesive otitis: how we do it. OBJECTIVES: Adhesive otitis is a chronic otitis media (OM) that consists of the adhesion of the tympanic membrane (TM) to the promontory. The aim of our study is to evaluate a new way of positioning subannular T-tubes (SATs) in patients affected by adhesive otitis. METHODOLOGY: This study enrolled 22 patients (average age: 36.7 yo, 2.5 SD; M/F ratio: 14/8) affected by unilateral chronic adhesive otitis. All of the patients underwent the positioning of a SAT and a Silastic@ sheet in the tympanic cavity. The clinical course was evaluated, considering otoscopic and audiological variations. RESULTS: In our series, only one case of extrusion of tubes with residual perforation of TM was recorded. Auditory outcomes were satisfying in 18/22 patients (81.8%). CONCLUSIONS: The proposed addition of a Silastic disk seems to avoid a new adhesion of the tympanic membrane to the promontory and, therefore, prevents treatment failures. A longer follow-up and a larger case series are needed to prove the efficacy of this surgical variation. Finally, the positioning of SATs can be considered as a valid and safe procedure for the treatment of adhesive otitis.

Mesalazine vanishing time from rectal mucosa following its topical administration.

To investigate how long and how much Mesalazine (M) is available inside the rectal mucosa following its topical instillation, in patients (pts) with Ulcerative Colitis (UC). Two rectal biopsies for M concentration were obtained from 45 UC pts in clinical remission and on oral M treatment (OT), before a 4g enema randomly given to consentient pts every day (Group A, 15 pts), every 2 days (Group B, 15 pts) and every 3 days (Group C, 15 pts). Two additional biopsies were taken 1, 2 and 3 days after the last enema in group A, B and C respectively, at least 10 days later. All biopsies were immediately frozen at -80°C for later assay by means of high-performance light chromatography (HPLC). Data were analyzed using Student's t-test. Mean values±standard deviation of M mucosal concentration (ng/mg of tissue) were 1.32±1.41, 56.1±39.2, 9.65±6.60, and 6.39±5.03 in pts receiving OT alone, groups A, B and C, respectively. Values in Group A were statistically higher (p<0.001) than those in Groups B and C while no differences were found between Groups B and C. Values of OT were lower than groups A, B and C. M mucosal concentration rapidly decreases 2 days after a 4g enema, but after three days is still higher than OT alone. These results may provide data which would be useful to plan topical therapy and improve adherence to treatment.

Identification of an isomer impurity in piperaquine drug substance.

A significant contaminant of the antimalarial drug piperaquine (1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]propane) has been identified using liquid chromatography-mass spectrometry (LC-MS) and 2D NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC). The impurity was identified as the positional isomer 1-[(5-chloroquinolin-4)-piperazinyl]-3-[(7-chloroquinolin-4)-piperazinyl]propane. The impurity is formed because of contamination of batches of 4,7-dichloroquinoline (a precursor in the synthesis of piperaquine) with 4,5-dichloroquinoline. The amount of impurity (peak area impurity/peak area piperaquine using LC-UV at 347 nm) in old batches of piperaquine and in Artekin (the combination of dihydroartemisinin-piperaquine) ranged from 1.5 to 5%.

Seasonal variations in onset of symptoms in Crohn's disease.

BACKGROUND: Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. PATIENTS AND METHODS: Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. STATISTICAL ANALYSIS: chi-square test, odds ratio (95% confidence interval). RESULTS: Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring-summer compared to autumn-winter (odds ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51; p<0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27). CONCLUSIONS: These data indicate that onset of Crohn's disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases.

Long-term oral plus topical mesalazine in frequently relapsing ulcerative colitis.

BACKGROUND: In cross-sectional studies, it was demonstrated that the therapeutic effect of mesalazine is closely related to its mucosal concentration. AIM: This study was carried out to verify in a longitudinal study if it was possible to improve the clinical course of ulcerative colitis at high risk of recurrence by increasing mucosal mesalazine concentration. METHODS: Eighteen consecutive ulcerative colitis patients on continuous oral 5-ASA treatment (2.4-3.2 g/day) in clinical remission who had had at least four moderate to severe relapses in the preceding 2 years (referred period) were assigned to assume oral (3.2-4.8 g/day) and topical (4 g/day) mesalazine in order to increase mucosal drug concentration and were followed up for 2 years (study period). The localisation of disease was 12 pancolitis, six left colitis. The number and severity of recurrences, number of visits and endoscopies, courses of steroids and days of hospitalisation were compared with those of the previous 2 years. Rank signed test for paired data was used for statistical analysis. RESULTS: The total number of recurrences was significantly lower during the study period in comparison with that of referred period (8 versus 80, respectively, p < 0.0001). No courses of steroids or hospitalisation were necessary during study period in comparison with those of referred period (0 versus 33, p < 0.0001; 0 versus 93, p = 0.03, respectively). A total number of 249 visits were done during the referred period and 116 during the study period (p < 0.0001) with a total of 87 endoscopies during referred period and 44 during study period (p < 0.0001). CONCLUSIONS: The continuous use of topical mesalazine associated with a high oral dosage significantly improves the clinical course of ulcerative colitis patients at high risk of relapse.

Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations.

OBJECTIVE: To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha (TNFalpha) monoclonal antibody (infliximab) in the treatment of spondyloarthropathy (SpA) associated with active and inactive Crohn's disease (CD). METHODS: Twenty four patients with SpA associated with active or inactive CD (16 active, 8 quiescent) were treated with anti-TNFalpha monoclonal antibody (infliximab) with repeated infusions for a period of 12-18 months. The treatment aimed at ameliorating the general musculoskeletal and spinal pain, controlling peripheral arthritis and enthesitis, decreasing the BASDAI score, modifying acute phase reactants, and reducing CD activity. RESULTS: Infliximab improved both gastrointestinal (p<0.01) and overall articular symptoms (BASDAI, p<0.01; general musculoskeletal and spinal pain, p<0.01; peripheral arthritis, p<0.01) in patients with active CD. Additionally, infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis (p<0.01) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers. Amelioration of gut and musculoskeletal involvement persisted for up to 12 months. CONCLUSION: Infliximab may act on the inflammation of entheses and of periarticular structures, which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA, suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD.

The stereoselective targeting of a specific enzyme-substrate complex is the molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by (R)-(-)-PPO464: a novel generation of nonnucleoside inhibitors.

The human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitor pyrrolopyridooxazepinone (PPO) derivative, (+/-)-PPO294, was shown to be active toward wild type and mutated HIV-1 RT and to act synergistically in combination with 3'-azido-3'-deoxythymidine (Campiani, G., Morelli, E., Fabbrini, M., Nacci, V., Greco, G., Novellino, E., Ramunno, A., Maga, G., Spadari, S., Caliendo, G., Bergamini, A., Faggioli, E., Uccella, I., Bolacchi, F., Marini, S., (1999) J. Med. Chem. 42, 4462-4470). The (+/-)-PPO294 racemate was resolved into its pure enantiomers, and the absolute configuration was determined by x-ray analysis. Only one enantiomer, (R)-(-)-PPO464, displayed antiviral activity against both the wild type and the K103N mutant HIV-1 RT and was found to interact exclusively with the reaction intermediate formed by RT complexed with both the DNA and the nucleotide substrates. Being the first compound of its class to display this behavior, (R)-(-)-PPO464 is the representative of a novel generation of nonnucleoside inhibitors. (R)-(-)-PPO464 showed significant synergism when tested in combination with other RT inhibitors and efficiently inhibited viral replication when tested against the laboratory strain HIV-1 IIIB or against either wild type or multidrug-resistant clinical isolates. Pharmacokinetic studies in mice and rats showed a more favorable profile for (R)-(-)-PPO464 than for the corresponding racemate. (R)-(-)-PPO464 was also found to easily cross the blood-brain barrier. The coadministration of the HIV-1 protease inhibitor ritonavir increased the bioavailability of (R)-(-)-PPO464, having little effect on its plasma and brain elimination rates.

Midfacial granuloma syndrome or an inflammatory non-specific disease? A case report.

We report a case of idiopathic midline destructive disease in a 57-year-old man. The patient had a non-specific histological pattern in biopsies obtained from the nose and upper lip, characterized by a granulomatous reaction with progressive destruction of the tissues. The patient's general medical history was non-contributory. Clinical and laboratory data did not support any feasible etiology for this destructive process. The patient was treated with prednisone until the discovery of type II diabetes mellitus (never diagnosed before) and was then in turn treated only with oral antidiabetic therapy. Follow-up controls revealed progressive reduction of the symptoms and of the nasal and lip lesions and total remission of symptoms up to 2 years after the onset of the disease. We discuss the diagnostic and subsequent therapeutic problems in the management of the midline necrotizing lesions.

[Morphological study of the palatine tonsils: clinical and histopathological considerations]. / Considerazioni cliniche ed istopatologiche in uno studio morfologico della tonsilla palatina.

This study examined 71 pediatric tonsillectomy patients through accurate case history and clinical examination, placing particular emphasis on pathologies concomitant to tonsillopathy. In an attempt to find anatomo-clinical correlations, these data were processed together with the results of a histomorphological study of thetonsil epithelium, performed on all tonsillectomy samples. The majority of these patients were females and none more than 13 years of age. Numerous pathologies were found associated with the tonsillopathy and in varying combinations, first and foremost of which was adenoid hypertrophy. Only approximately one fifth of the patients did not show any concomitant pathology of note. All patients presented a history of recurrent pharyngotonsillitis (at least 4 episodes a year) with symptoms arising from 1 to 10 years prior to surgery. The concomitant pathologies included: respiratory, cutaneous and food allergies, asthma, obstructive sleep apnea, rheumatic diseases, etc. From the histomorphological point of view, particular modifications were found in the follicle epithelium and interstitial cells of the palatine tonsil. An exasperated fibrotic interstitial reaction and chronic duration of the disease appeared to prevent tonsil filter function, facilitating chronicization of the tonsillopathy or onset of recurrent infections and concomitant allergies. In the allergic patients the tonsil epithelium was thickened and compact and showed various degrees of chorion edema, in agreement with what is found in the literature. On the contrary, few morphostructural palatine tonsil mutations were found in those subjects which did not present any concomitant pathology or were affected by tonsillopathy of brief duration. All the histomorphological modifications encountered appear related to the individual patient history, confirming the hypothesis that tonsil epithelium can not only condition the evolution of tonsillopathy--reflecting the effect of various factors--but, above all, it directs the immune response, thus playing a role in the development of various concomitant pathologies.