The relationship between mucosal immunoresponse and clinical outcome in patients with recurrent upper respiratory tract infections treated with a mechanical bacterial lysate.

This open prospective study aims to evaluate whether a therapy with a polyvalent mechanical bacterial lysate (PMBL) could be associated to the enhancement of the locoregional immunoresponse in patients with recurrent upper respiratory tract infections. Forty patients (23 females and 17 males) were enrolled, 33 of whom concluded the study. The duration of the study was six months and each patient was visited five times. Twenty-six patients had an objective improvement in clinical and medical locoregional conditions, while in seven patients the treatment did not result in an objective amelioration. Twenty-five out of 27 patients with clinical response were characterized by an increase of specific antibodies against PMBL antigens in salivary fluids. Only two patients, with a non-significant clinical result, had a slight increase in the concentration of salivary specific IgA. The association between PMBLspecific immunoglobulin titers and clinical results was significant for IgG and IgA, but not significant for IgM. Th1 switch was detected only in patients with clinical amelioration, while the Th0 phenotype was observed in three responder and four non-responder patients. Weak Th2 polarization was also observed in one clinical responsive patient. The capacity of effectively opsonizing living bacteria was detected in samples derived from responder patients. These results suggest that PMBL treatment was able to trigger an efficient and well-targeted immune-response resulting in positive clinical outcome of the patients treated.

The clinical and organisational appropriateness of tonsillectomy and adenoidectomy-an Italian perspective.

The objective of the document is to define the most appropriate indications and health-care procedures for tonsillectomy and adenoidectomy and is intended for use by paediatricians, general practitioners, and otolaryngologists involved in the treatment of adenotonsillar pathologies. After a systematic review and grading of evidences from the literature, the document was drafted by a multidisciplinary panel with identified key clinical questions related to indications for surgery, surgical and anaesthesiology procedures, clinical management and organizational issues. It should be stressed that the document was not aimed at providing graded recommendations per se, but to offer suggestions and advices. The document will be updated within December 2006.

Neuronal activity in medial geniculate body following single semicircular canal stimulation.

Unit activity of medial geniculate body (MGB) neurons was recorded in curarized guinea pigs following separate thermal stimulation of single separate thermal stimulation of single semicircular canals. The same neurons were also tested with acoustic stimuli (clicks). Convergence on MGB units of inputs arising from several (2-6) canals was observed. Convergence of acoustic and vesticular influences was also demonstrated. After labyrinthine stimulation MGB neurons usually displayed inhibitory responses and, less frequently, activation. Clicks induced brief burst of activity. Our data indicate the existence of a wide vestibular projection in the MGB.

Antibiotic prophylaxis in ear, nose and throat surgery: a comparison of a single preoperative dose with three peri-operative doses of ceftazidime.

An open prospective randomized trial was conducted in three Italian ear, nose and throat (ENT) surgery departments on 120 patients aged 10 to 84 years, to compare a single pre-operative dose vs. three peri-operative doses of ceftazidime in surgical prophylaxis. Sixty patients in group I received 1 g ceftazidime intramuscularly (im) or intravenously (iv) 1 h before surgery, and 60 in group II received three 1 g doses of ceftazidime, im or iv, 1 h before, and 6 and 12 h after surgery. Post-operative infections were observed in six group I patients (10.1%) and seven group II patients (11.6%). All infections arose in patients who had undergone 'moderate-risk' (6.7%) or 'high-risk' surgery (30.5%). We conclude that a single pre-operative 1 g dose of ceftazidime is as efficacious as multiple peri-operative doses in the prophylaxis of infectious complications following this type of surgery.

A multicenter trial of specific local nasal immunotherapy.

OBJECTIVE: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters. STUDY DESIGN: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months. METHODS: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen. The specific treatments were self-administered using an insufflator in two phases (phase 1: increasing doses; phase: 2, maintenance dose). Patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test results confirmed that this difference was statistically significant. The rhinomanometric analysis gave positive results for the treated group mainly in LNIT for mites. No differences in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is effective for allergic rhinitis and appears to offer considerable advantages over other hyposensitization methods. It can be done at home, patient compliance is good, and the treatment is safe.

Gemcitabine, cisplatin, and radiation in advanced, unresectable squamous cell carcinoma of the head and neck: a feasibility study.

Alternating chemoradiotherapy was shown by our institution to be superior to standard radiation in patients with nonsurgical squamous cell carcinoma of the head and neck (SCC-HN). Gemcitabine has shown in vitro and in vivo radiosensitizing properties, synergistic activity with cisplatin, and cytotoxic activity against SCC-HN. Thus, the authors tested the feasibility and antitumoral activity of a modified alternating chemoradiotherapy program that includes gemcitabine. Fourteen patients with stage IV (nine patients) or relapsed after surgery (five patients) unresectable SCC-HN were enrolled. None had previously received chemotherapy or radiotherapy. The treatment plan consisted of cisplatin, 20 mg/m2/day, days 1 to 5, weeks 1 and 5, and gemcitabine 800 mg/m2, day 5, weeks 1, 2, 3, and 5, 6, 7. Radiation was administered during weeks 2, 3, and 4 and 6, 7, and 8 with conventional fractionation up to 60 Gy. At the end of the combined therapy, patients had to receive two additional courses of cisplatin, 20 mg/m2/day, and fluorouracil, 200 mg/m2/day, for 5 days every 21 days. All the patients are evaluable for toxicity and 11 for response. Main grade III-IV toxicities and frequencies were: neutropenia (79%), neutropenia with fever (50%), thrombocytopenia (57%), anemia (35%), mucositis (100%), and cutaneous toxicity (14%). Ten patients (71%) had a weight loss greater than 10%. All but two patients needed hospitalization and tube feeding or parenteral nutrition. The median relative dose intensity of gemcitabine actually delivered was 83%. Two patients died 1 month after the end of treatment before the final evaluation. One patient died of sepsis during the additional cisplatin and fluorouracil courses before response assessment. Ten patients reached a complete response (intention to treat: 71%), and 1 patient had a partial response (9%). At a median follow-up of 34 months, the actuarial 3-year progression-free survival and overall survival are 41% and 63%, respectively. The estimated 3-year locoregional control is 70%. Considering the expected poor prognosis of the enrolled patients, this combined regimen showed an impressive antitumoral activity, but the severity of acute local and hematologic toxicity correlated makes the exportation of this regimen unproposable. However, the activity observed warrants the exploration of different, less toxic, chemo-radiotherapy programs including gemcitabine.

Neurotological auditory brain stem response findings in human immunodeficiency virus-positive patients without neurologic manifestations.

Neurologic manifestations of human immunodeficiency virus (HIV) infection, rather than being a late complication of the disease, are principally correlated with the early central nervous system (CNS) localization of HIV. The CNS may be infected in the early stages of acquired immunodeficiency syndrome (AIDS) without evidence of neurologic disorders. Evoked potentials (visual, auditory, and somatosensory) and electronystagmographic test batteries have proven to be very sensitive in showing subclinical CNS disorders due to HIV. In this study, auditory brain stem response (ABR) and electronystagmographic test battery findings (smooth pursuit, saccades, caloric test) were performed in 29 neurologically asymptomatic, HIV-positive subjects at different stages of the disease. Compared to results of a control group, the ABR latencies of waves V, I, and III and interpeaks I-V and III-V were significantly increased in HIV patients. The same parameters did not differ significantly among the stages of the disease. In HIV-positive subjects, the accuracy of saccades was significantly reduced, while latency was normal. The velocity and the gain of pursuit were significantly reduced in HIV-positive patients, and 15 of 29 patients showed corrective saccades. Caloric tests revealed qualitative nystagmus abnormalities in 82% of HIV patients, while quantitative parameters were normal. The present results confirm that CNS involvement by HIV occurs early in the course of the disease. In particular, HIV does not seem to affect the labyrinth or the eighth cranial nerve, as demonstrated by the normality of the I-III value of the ABR and of the quantitative parameters of the caloric responses, but it does appear to involve the brain stem acoustic pathways, pontocerebellar pathways, and supratentorial areas.

[The clinical problems of bacterial infections of the upper respiratory tract]. / Problemi clinici delle infezioni batteriche delle prime vie respiratorie.

ORL inflammations present particular pathogenetic and clinical characteristics due to the close anatomic and physiological connection among them and to their particular anatomic characteristics. The ear communicates with the rhinopharynx through the Eustachian tube, and this relationship explains how bacterial infections of the upper respiratory tract can cause otitis and how tubal dysfunctions are often responsible for chronic ORL infections, also favoured by the microcavity structure of the middle ear and the mastoid bone. Also the macro- and microcavity anatomic structure of the paranasal sinuses favours chronic infectious diseases, and their adjacency with the endocranial and facial structures justifies the secondary complications of these infections. The palatine tonsil and other structures of the Waldeyer's lymphatic ring play an important immune role in the first respiratory and digestive tract, and infections occurring in these structures (for example, streptococcal infection) can cause pathologies such as rheumatic disease. Other ORL infections are connected to immunodeficiency or atopy.

[Otoneurological manifestations in Fhar's disease. A case report]. / Manifestazioni otoneurologiche nel morbo di Fhar. Descrizione di un caso clinico.

Fhar's disease is a rare idiopathic CNS pathology characterized by widespread calcifications of the basal ganglia, cerebellar nuclei and endocranial vessels. The origin of this disease is unknown and a lack of thyroid and parathyroid pathologies is the main statement. From the clinical point of view, extrapyramidal manifestations are common while vertigo and equilibrium disorders are rare. In the present case vertigo and disequilibrium were the main symptoms. Fhar's disease was diagnosed by CT and MRI showing calcification of the basal ganglia without any metabolism disorders or thyroid and parathyroid pathology. A battery of neurotological tests showed alterations of VOR and ocular movement. In particular the saccades movements showed significant hypometria while the smooth-pursuit showed gain diminution and corrective saccades. These anomalies imply dysfunction of sub-cortical centers regulating and modulating ocular movement. VOR alterations included both qualitative anomalies of nystagmus (i.e. dysrhythmia, square waves) and quantitative alterations (i.e. bilateral deficit response to caloric and rotatory stimuli). These alterations could be due to the impairment of cerebellum-vestibular and vestibular-thalamic pathways. Acoustic evoked potentials (ABR, MLR) ruled out central acoustic pathway dysfunction.

[Labayle's supracricoid partial laryngectomy in the treatment of laryngeal cancer: personal experience and long term follow up]. / Laringectomia ricostruttiva sopracricoidea secondo Labayle: esperienze personali e valutazione di pazienti a prolungato follow-up.

The present study was carried out to assess the indications and to evaluate the functional and oncological results of the supracricoid laryngectomy with crico-hyoid-pexy proposed by J. Labayle. This technique consists of a sub-total laryngectomy where the cricoid cartilage, the hyoid bone and at least one of the arytenoids are spared. These structures can then be reassembled into a "neo-larynx", thus preserving respiration and phonation. The present paper deals with 23 laryngeal carcinomas: 13 glottic (2 T1bN0, 6 T2N0, 1 T2N1, 1 T2N1, 3 T3N0) and 10 supraglottic (4 T2N0, 3 T2N1, 3 T2N2). The follow-up shows a 5-year overall actuarial survival rate of 80.65%. The authors agree that when performed under very precise indications the crico-hyoid-pexy is a useful alternative to both radiotherapy and the extended-partial or total laryngectomy in the treatment of laryngeal carcinoma. It also appears useful in treating selected cases of post-surgical or post-radiotherapy recurrences.

[Analysis of the cellular infiltrate and epithelial class I and II molecular expression in edematous type nasal polyps]. / Analisi dell'infiltrato cellulare e della espressione epiteliale di molecole HLA di istocompatibilitá di classe I e II in polipi naso-sinusali di tipo edematoso.

Although in the last few years histopathological, immunohistochemical and immunological studies on nasal polyps have been carried out by several Authors, the etiology of these formations still remains unknown. Nasal polyps have a very characteristic structure and have been classified in three histologic types: edematous, glandular and fibrous. In the present report, 11 nasal polyps of edematous type, representing 61% of total number of collected polyps, were studied employing immunohistochemical methods. All the examined polyps were similar in histology and positivity pattern for HLA molecule expression. The edematous core appeared infiltrated (149 cells/mm.2) mainly by eosinophils (> 90%), whereas the peripheral subepithelial connective tissue contained cellular clusters (416 cells/mm2.) made up of different subsets of hematic cells (30.8% were monocytes-macrophages and 48.6% were lymphocytes largely represented by CD4+ cells). On the contrary, mast cells were quite rare (on the average 1.7 cells/mm2.) and located near T cell clusters. The epithelial positivity for HLA-DR and HLA-A,B,C molecules showed a characteristic discontinuous pattern. In the same patient, controlateral nasal mucosa showed a histological structure very similar to that of polyps. The above data suggest that the presence of polyps is the result of an inflammatory process brought about by a complex array of cellular and humoral components.

[Nasal polyps: comparative immunological study of polyps with different histopathologic types]. / I polipi naso-sinusali: studio immunoistologico comparativo di formazioni con differente tipologia istopatologica.

Cellular Infiltrate as well as class I and II HLA molecule expression, on 22 nasal polyps and on 12 samples of corresponding hypsilateral mucous membrane were studied by means of immuno-histological methods. These nasal polyps were classified according to their histopathological structure. Five polyps, with a fibrous connective core infiltrated by cells of the monocyte-macrophage lineage, were classified mixed. The remaining seventeen polyps were characterized by the presence of central oedematous connective tissue infiltrated almost exclusively by eosinophils and either contained (glandular type) or did not contain (oedematous type) glands. A comparative study of different types of nasal polyps and corresponding hypsilateral nasal mucous membranes was carried out on atopic and non-atopic patients. No correlation between atopic status and polyp presence or polyp typology was found. On the other hand, different polyp types appear to have a structural correlation with the corresponding hypsilateral mucous membrane regarding infiltrate cell type, oedematous or fibrous connective tissue presence and expression of on HLA antigen positivity pattern. The characteristic histological structure of hypsilateral mucous membranes in patients with different types of polyps appeared to be brought about by a multifactorial etiology involving mucosal hyperreactivity. Lastly, both polyps and parapolypal nasal mucous membranes were found to be infiltrated mainly in the peripheral subepithelial connective tissue by lymphocytes (55%) as well as by other leukocyte types. The presence of growth factors capable of enhancing an increase of fibroblasts, endothelial cells, together with focal distrupture on the basal membrane, might well be a general mechanism responsible for polyp sprouting.

[Taste disorders in forensic medicine]. / Alterazioni del gusto in medicina legale.

Taste disorders can a rise from lesions of peripheral receptors, taste control pathways or cortical area involvement. Among peripheral lesions, trauma of the tongue and oropharynx are the most common. Iatrogenic lesions of facial and glossopharingeal nerves are very important in Forensic Medicine, while there are different opinions about taste alterations due to head injuries; hypogeusia associated to smell disorders are found in 0.4-0.5% of patient after head trauma with good prognosis (90% healing) while qualitative disorders are more common (30%). The Authors describe clinical methodologies for taste evaluation and their application in Forensic Medicine. Forensic estimation of taste disorders con be classified by two main groups: study of cause relation between the occurrence and damage and quantitative valuation of the damage in three different juridical ambits: Penal, Civil, Insurance and foresight. In Penal Right taste damages could be classified among personal lesion crimes and can be classified as serious (permanent injury of taste) ore very serious (complete lost of taste function). Italian Legislation equipare the 5 sense organs. In Civil Right evaluation the so-called "biologic damage" and working ability are considered; this means very different evaluations. In the most recent baremes, generic damage is estimated by different Authors from 0 to 10% while with regard to specific working capacity, common evaluation criteria does not exist. In Insurance taste disorders evaluation is based only on working ability and not on biologic damage. In the previdenzial ambit, taste disorders are not even included in the most recent tables of permanent invalidity estimation. The Authors propose new and more efficacious valutation criteria for taste disorders in all ambits, hoping for more interest in the Forensic aspects of taste, a too often forgotten sensory function.

[Case report: pleomorphic adenoma of the lateral nasal wall]. / Su un caso di adenoma pleomorfo della fossa nasale.

Pleomorphic adenoma is a tumor which most often originates from one of the major salivary glands; it is rarely located in the lacrymal glands and it is highly exceptional in the nasal cavity. Cases of pleomorphic adenoma in the nasal cavity have been described by Spiro (40 cases), Compagno and Wong (40 cases) and Suzuki et al. (41 cases). This type of tumor generally originates from the septal mucosa even though the seromucosal glands are mostly located in the lateral nasal wall. This pathology is more frequently found in females. The clinical signs of this tumor are non specific, slow unilateral nasal occlusion, rhinorrhea and, at times, epistaxis. Evolution is generally local although locoregional and distant metastases have been described in the literature. This sort of tumor has no specific appearance and thus diagnosis is based on histology. Indeed, microscopically nasal pleomorphic adenoma differs from salivary gland adenoma for the predominance of the cellular component over the connective component. The epithelial cells are small, oval-shaped and often arranged in cordons; they are sometimes organized in small acinous structures. The connective component can be mixoid, condroid or collagenous; follicles with squamous metaplasia and mitosis are rare. Histologically differentiating this disorder from olfactory esthesione-uroblastoma can prove difficult; the lack of extra cellular neurifibrillar structures, neurotubules and neurosecretory granules in nasal pleomorphic adenoma are the main distinguishing criteria. The present work reports a case of a 45-year-old man who had suffered of an increasing unilateral nasal obstruction from 1 year. Endoscopic examination showed a smooth surface neoplasm involving the entire nasal cavity. CT scan showed the deformation of the medial bone wall of the maxillary sinus and of the ethmoid although without any osteolysis. Median maxillectomy surgical exeresis of the neoplasm was performed with the facial degloving technique. Histology revealed a 5 cm pleomorphic adenoma originating from the lateral nasal wall. This origin is extremely rare because this tumor generally originates in the nasal septum. Immunohistochemical stains proved positive for epithelial membrane antigen (MNF 116), for myoepithelial cells (PS100) and for stromal cells (Vimentine) with the epithelial elements predominating. After 9 months of follow-up the patient is still disease free.

[The interactions between metal stapes prostheses and high-intensity magnetic fields during magnetic resonance tomography]. / Interazioni tra protesi stapediali metalliche e campi magnetici di elevata intensità in corso di tomografia a risonanza magnetica.

The ever-increasing use of magnetic resonance tomography (MR) as an investigation mean has created a new interest in the biological effects of magnetic fields (MF) and in finding protective measures to be taken in their event. At the moment, use of MR is contraindicated in the presence of pacemakers, vascular clips, liquoral shunts and orthopedic prostheses, all of which may be dislocated by the MF created by MR or may interact with the MF itself creating distorted or falsified images. The aim of our study was to verify if metallic stapedectomy prostheses are dislocated by the MF and if they produce enough interference to falsify MR images. Five types of metallic stapedial prostheses exposed to a MF of 0.5T were studied. We may conclude from our results that MR does not create any otological risks for patients with these prostheses in that none of them were dislocated during exposure. However, all the prostheses studied did instead bring about alterations in the MF and the MR image to varying degrees. In some cases (Robinson) there was notable image distortion, while in others (Schuknecht wire teflon and platinum piston) the distortion was practically negligible. It is our opinion, however, that even if the image distortion does not interfere with routine MR, use of prostheses made of materials not affected by MF are advisable in view of an eventual development of visualization of the labyrinth and intratemporal facial nerve portion with MR.

[Wegener's and Stewart's granulomatosis: a case report of Stewart's granulomatosis]. / Le granulomatosi centrofacciali di Wegener e di Stewart: su un caso clinico di granuloma centrofacciale di Stewart.

Wegener's and Stewart's diseases are two rare pathologies of unknown origin; both can cause disruptive facial lesions. Wegener's disease is a systemic pathology and generally involves the kidneys and lungs. Granulomatosis lesions are characterized by the necrotizing vasculitis involving the small vessels. From a diagnostic point of view the systemic features of Wegener's disease and the specific immunological findings (i.e. IgG autoantibodies vs. monocyte and neutrophil cytoplasm) make it possible to diagnose the disease precisely. Stewart's disease can be differentiated from Wegener's disease by the absence of any systemic lesions and the lack of necrotizing vasculitis. Pathogenesis of the disease is still unknown although immunohistochemical findings indicate that it is related to extranodal Tcell lymphomas. Stewart's disease is very aggressive with massive destruction of the midface tissues and prognosis is very poor (from a few months to 23 years). Surgery is generally ineffective in such disorders. The treatment for Wegener's disease includes the use of systemic steroids, immunosuppressive drugs and the sulfametoxazole-thrimethoprime association while radiotherapy associated with chemotherapy appears most effective in Stewart's disease. The authors describe a case of Stewart's disease prevalently involving the nasal cavities, ethmoid and paranasal sinuses. Diagnosis was made on the basis of immunohistochemical, histomorphological and immunological data. Treatment--based initially on systemic steroids with the association thrimethoprimsulfometoxazole--induced significant disease remission. Subsequent use of cytostatic drugs has made it possible to control the disease progression to date.

[Alternating chemotherapy and daily multiple-fraction radiotherapy in the treatment of advanced spinocellular carcinoma of the head and neck]. / Alternanza di chemioterapia e radioterapia a frazioni multiple giornaliere nella cura di carcinomi spinocellulari avanzati del distretto cervico-cefalico.

From January 1987 to May 1988 sixteen pts with advanced squamous cell carcinoma of the head and neck received a combined treatment based on an alternation of chemotherapy and MFD--radiotherapy. The chemotherapy regimen consisted of CDDP 20 mg/m2 and 5-FU 200 mg/m2 i.v. push, from day 1 to day 5 during weeks 1, 5 and 9. Radiotherapy was administered in two courses of 32 Gy each (total dose 64 Gy), during weeks 2-3 and 6-7. Each course was given in 2 fractions per day, five days per week. All sixteen patients could be evaluated for toxicity and fifteen for response. The following were observed: 7 CR, 6 PR, 1 SD and 1 PD. The overall response rate was 86.6%. Toxicity was high; 43.7% of the patients developed grade III-IV mucositis. These results suggest that CDDP and 5-FU alternating with MFD-radiotherapy is feasible, although new, less toxic scheduling must be determined.