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Purpose Intranasal cocaine is known to potentially lead to midline destructive lesions. The present systematic review was undertaken to systematically define the localization of cocaine-induced midline destructive lesions and their prevalence and to propose a practical classification of these lesions. Methods A PRISMA-compliant systematic review was performed in multiple databases with criteria designed to include all studies published until March 2021 providing a precise definition of cocaine-induced midline lesions in humans. We selected all original studies except case reports. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for lesion localization, patients’ demographics, exposure to cocaine, and relationship with external nose destruction. Results Among 2593 unique citations, 17 studies were deemed eligible (127 patients). All studies were retrospective case series. The destructive process determined a septal perforation in 99.2% of patients. The distribution prevalence decreased from the inferior third of the sinonasal complex (nasal floor and inferolateral nasal wall, respectively, 59% and 29.9% of patients) to the middle third (middle turbinate and ethmoid, 22.8% of patients), and ultimately to neurocranial structures (7.9% of patients). Nasal deformities were inconsistently reported across reviewed studies. Cocaine use duration, frequency, and status were reported only occasionally. Conclusion Based on the distribution prevalence observed, we propose a four-grade destruction location-based classification. Future prospective studies following the evolution of cocaine-induced lesions are needed to validate our classification, its relationship with lesion evolution, and whether it represents a reliable tool for homogeneous research results reporting.

The homicide of the female partner followed by suicide of the perpetrator (Intimate Female Partner Homicide Suicide - IFPHS) has been a growing phenomenon over last years, but its psychosocial and psychopathological aspects have not been analyzed in-depth yet.The aim of this study was to investigate common psychopathological elements in different IFPHS and a specific risk profile for both the couple and the male partner, with the possibility to define a new serial mental condition not classified to date.A series of 50 cases of greater media coverage was reconstructed from the Italian newspapers in the period from 2009 to 2019 and information was collected through a predefined form. The characteristics of the perpetrators and the modalities through which the events occurred have been considered.No definite mental disorder is present in the history of almost all cases. A more common psychological profile is found for the homicide/suicide male partner, mainly characterized by jealousy, possessiveness, mood reactivity, rage, and impulsiveness.It can be hypothesized that such a severe act may express a form of mental disorder not yet classified, with main features of an acute state of mixed depressive mood, emotional discontrol and aggressive impulsiveness, on a personality basis of jealousy and possessiveness, possibly reinforced by previous dependent traits of the female partner. But the methodological limitations of gathering information from the press make it necessary the study in depth, based on more direct and objective methodologies, of such a highly dramatic and heterogeneous phenomenon.

Purpose This study aimed to examine the relationship between the sphenoid sinus (SS) and surrounding vital structures such as the internal carotid artery (ICA) and optic nerve canal (ONC) as well as the types of attachment of the sphenoidal septa onto these structures. Methods In total, 230 computed tomography (CT) scans were reviewed to study the type of sphenoid sinus pneumatization (SSP), the protrusion and dehiscence of the ICA and ONC, the relationship between the sphenoidal septa and surrounding vital structures as well as pterygoid recess pneumatization (PRP). Results The most common SSP was sellar type (58.7%). The rates of protrusion and dehiscence of the ICA were 26.3 and 0.4%, and for the ONC, they were 13 and 1.5%, respectively. The ICA and ONC were most protruded and dehiscent in more extensive SSP. In 21.6% of patients, the intersphenoidal septa (IS) were attached to the wall of the ICA and in 8.6% they were attached to the wall of the ONC. The attachment of IS to the ICA correlated statistically significantly (p Conclusion To reduce the risk of injury and complications during endoscopic sinus surgery (ESS), surgeons should consider using CT to identify possible bulging and dehiscence of the ICA/ONC and their relationship to the extent of SSP and also to establish the presence of deviation of the sphenoid septum, and the presence of accessory septa.

Background Odontogenic sinusitis affects a significant proportion of patients with paranasal sinus infections. Nevertheless, no shared diagnostic criteria for this condition have yet been implemented and published studies differ in their definition of the disease. Objective The present systematic review of the literature was undertaken to characterize and analyze the different diagnostic criteria currently employed for odontogenic sinusitis. Methods Systematic searches for studies published between 2009 and 2019 were performed in Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases. Search criteria were designed to identify all studies focusing, even partially, on odontogenic sinusitis. Human original studies except single case reports published in the English, French, German, Spanish, or Italian language were included. We removed duplicate abstracts and conducted full-text reads, data extraction, and quality assessment procedures (using the Oxford Centre for Evidence-based Medicine levels of evidence and National Heart Lung and Blood Institute Study Quality Assessment Tools). We reviewed articles for diagnostic criteria, both in terms of definition and etiology identification. Results Among 1,000 unique citations, 63 studies were deemed eligible. Most articles (n = 45) were retrospective case series; a single randomized clinical trial was available. Only 49 studies reported diagnostic criteria, yet relied marginally on published guidelines (n = 10 articles) for identifying sinusitis, often choosing instead to develop their own clinical (n = 15 articles), endoscopic (n = 12 articles), and/or radiologic (n = 30 articles) criteria. For odontogenic focus identification, 14 papers required a multidisciplinary evaluation, 11 papers required a time relationship between dental procedures and sinusitis, 24 papers required oroscopy and/or dental evaluation, and 53 papers required computed tomography. Conclusions Current diagnostic criteria for odontogenic sinusitis are extremely heterogeneous. Establishing shared diagnostic criteria aimed at defining both sinusitis and related odontogenic foci would spur collaboration between investigators and support more comprehensive outcomes evaluations together with a better understanding of treatment options.

Objectives: Paranasal sinus fungus ball is a common non-invasive mycosis with excellent long-term surgical treatment results. The present systematic review and meta-analysis were undertaken to define current treatment concepts and success rates in paranasal sinus fungus ball treatment. Methods: Systematic searches were performed in multiple databases with criteria designed to include all studies published until May 2020 focusing on paranasal sinuses fungus ball treatment in humans. We selected studies including at least 10 patients, specifying treatment modalities, providing a minimum 6-month follow-up, and objectivating treatment success. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates. Success rates were pooled in a random effect meta-analysis and compared according to the use of intraoperative sinus lavages and postoperative antibiotics. Results: Among 740 unique citations, 14 studies were deemed eligible. Most (n = 11) were retrospective case series. All studies relied on endoscopic sinus surgery. Intraoperative lavages were proposed in 10 studies and postoperative antibiotics in 7 (for all patients in 5 studies and for selected patients in 2). No significant heterogeneity was observed between results (Cochran’s Q P = .639, I2 test = 0). Treatment success rate was 98.4% (95% confidence interval 97.4%-99.3%). Intraoperative sinus toilette and postoperative antibiotics didn’t significantly improve the success rate. Conclusion: Endoscopic sinus surgery shows excellent results in fungus ball treatment. Further prospective studies might help further reducing antibiotics prescriptions in these patients and improve their management.

The purpose of this study was to correlate acute invasive fungal rhinosinusitis (AIFRS) and chronic invasive fungal rhinosinusitis with underlying diseases, aetiological microorganisms, clinical symptoms, radiological findings, and surgical and medical treatment to determine the subset of patients who require more accurate diagnostic investigation and to prevent irreversible complications.This retrospective monocentric study included 17 patients who underwent endoscopic sinus surgery evaluated by paranasal computed tomography and magnetic resonance imaging. Age, sex and symptoms, and location of the invasive fungal infection and the causative fungus were analysed.In total, 4 patients were affected by the AIFRS form, and 13 by the chronic form. Diabetes mellitus was reported in 41.17% of cases, and haematological diseases in 23.52%. The maxillary sinuses were involved in 47.05% of cases and sphenoidal sinuses in 52.94%; Aspergillus fumigatus was the fungus in 76.47% of cases, and Zygomycetes in 23.53%.An understanding of the different types of fungal sinusitis and knowledge of their features play a crucial role in reaching prompt diagnosis and initiation of appropriate therapy, which is essential to avoid a protracted or fatal outcome.Definizione e gestione della rinosinusite fungina invasiva: uno studio retrospettivo monocentrico.Nonostante i progressi in termini di trattamento, la mortalità nei casi di rinosinusite fungina invasiva rimane elevata, pertanto, scopo dello studio è stato correlare le forme acute invasive e quelle croniche con patologie concomitanti, agenti eziologici, i sintomi clinici, radiologia e trattamento, al fine di identificare e trattare i pazienti con prognosi peggiore.Il seguente studio retrospettivo monocentrico ha incluso 17 pazienti sottoposti a chirurgia endoscopica sinusale, valutati mediante TC e RM e analizzati per età, sesso, sintomi, sede dell’infezione fungina invasiva e microrganismi eziologici.4 pazienti sono risultati affetti dalla forma invasiva acuta,13 pazienti dalla forma cronica. Il diabete mellito è stato riscontrato nel 41,17% dei casi, malattie ematologiche nel 23,52%. I seni mascellari sono risultati coinvolti nel 47,05% dei pazienti e seni sfenoidali nel 52,94%; Aspergillus ha provocato il 76,47% dei casi, Zigomiceti il 23,53%.Un’adeguata comprensione dei diversi tipi di sinusite fungina e la conoscenza delle loro caratteristiche svolgono un ruolo cruciale ai fini di una diagnosi precoce e l’avvio di una terapia appropriata con lo scopo di ridurne la mortalità.

Introduction: Previous studies have reported a diverse range of threshold values for blood eosinophilia. In addition, a single predictive biomarker for eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) has not yet been identified. Objectives: The aim of this study is to compare the clinical characteristics of ECRSwNP and non-ECRSwNP to evaluate the preoperative risk of tissue eosinophilia of chronic rhinosinusitis with nasal polyps (CRSwNP) through a multiparametric statistical analysis. Methods: One hundred ten patients with evidence of chronic polypoid rhinosinusitis were included in this study and clinical records were retrospectively reviewed. Eosinophilic CRSwNP was diagnosed based on the presence of at least 10 eosinophils per high-power field. The demographic and clinical features of ECRSwNP and non-ECRSwNP are described. The values of blood eosinophilia as predictors of tissue eosinophilia have been identified using receiver operating characteristic curves. As the predictive value of the identified cutoff through regression analysis was low, we evaluated whether other risk factors could be statistically associated with ECRSwNP, and from this, a new predictive model was proposed for the identification of eosinophilic nasal polyps before surgery. Results: We found that the best method for predicting ECRSwNP is based on a model having asthma, blood eosinophil percentage, posterior ethmoid value in Lund-Mackay score, and modified Lund-Kennedy score as explanatory variables. Conclusions: This study provides new data for a better understanding of the polypoid CRS endotypes, and the proposed model allows the endotype to be identified preoperatively.

Background Because nasal function and shape are so closely intertwined, quantitative assessments can better define their relationship and how they are affected by septorhinoplasty. Objective The aim of this prospective study was to perform an analysis of the nasal airflow resistances and a three-dimensional (3D) evaluation of the soft-tissue changes after closed septorhinoplasty. Methods Before surgery (TO) and 6 months after closed septorhinoplasty (Tl), 30 patients underwent symptoms evaluation by means of the Italian version of the Nasal Obstruction Symptom Evaluation scale, endoscopic fiberoptic nasal examination, and visual analog scale for subjective assessment of nasal obstruction. Nasal airflow resistances were investigated with active anterior active rhinomanometry. A 3D laser scanner was used to evaluate facial soft-tissues, with specific nasal points and angles. Results Subjective nasal obstruction decreased. Anterior active rhinomanometry demonstrated a reduction in total inspiratory and expiratory resistances between T0 and T1 but without statistical significance. The significance was still absent after decongestion, excluding turbinate hypertrophy as a cause of failed objective amelioration of nasal resistance. Facial laser scanning showed statistically significant reduction of the superior nasal width and superior alar angle, and a weak negative correlation between the superior alar angle and nasal resistances. Conclusion The absence of objective reduction of nasal airflow resistances could be the result of concurrent surgery on nasal septum and nasal valve. In particular, the ameliorating effect on nasal airflow resistances is counterbalanced by the worsening effect of the narrowing of nasal valve.

Glioblastoma Multiforme (GBM) is an incurable malignancy. GBM patients have a short life expectancy despite aggressive therapeutic approaches based on surgical resection followed by adjuvant radiotherapy and concomitant chemotherapy. Glioblastoma growth is characterized by a high motility of tumour cells, their resistance to both chemo/radio-therapy, apoptosis inhibition leading to failure of conventional therapy. Cancer Stem Cells (CSCs), identified in GBM as well as in many other cancer types, express the membrane antigen prominin-1 (namely CD133). These cells and normal Neural Stem Cells (NSC) share surface markers and properties, i.e. are able to self-renew and differentiate into multiple cell types. Stem cell self-renewal depends on microenvironmental cues, including Extracellular Matrix (ECM) composition and cell types. Therefore, the role of microenvironment needs to be evaluated to clarify its importance in tumour initiation and progression through CSCs. The specific microenvironment of CSCs was found to mimic in part the vascular niche of normal stem cells. The targeting of GMB CSCs may represent a powerful treatment approach. Lastly, in GBM patients cancer-initiating cells contribute to the profound immune suppression that in turn correlated with CSCs STAT3 (CD133 + ). Further studies of microenvironment are needed to better understand the origin of GMB/GBM CSCs and its immunosuppressive properties.

Alkaptonuria (AKU) is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2-dioxygenase activity in the liver. This leads to an accumulation of homogentisic acid (HGA) and its oxidized derivatives in polymerized form in connective tissues especially in joints. Currently, AKU lacks an appropriate therapy. Hence, we propose a new treatment for AKU using the antioxidant N-acetylcysteine (NAC) administered in combinations with ascorbic acid (ASC) since it has been proven that NAC counteracts the side-effects of ASC. We established an in vitro cell model using human articular primary chondrocytes challenged with an excess of HGA (0.33 mM). We used this experimental model to undertake pre-clinical testing of potential antioxidative therapies for AKU, evaluating apoptosis, viability, proliferation, and metabolism of chondrocytes exposed to HGA and treated with NAC and ASC administered alone or in combination addition of both. NAC decreased apoptosis induced in chondrocytes by HGA, increased chondrocyte growth reduced by HGA, and partially restored proteoglycan release inhibited by HGA. A significantly improvement in efficacy was found with combined addition of the two antioxidants in comparison with NAC and ASC alone. Our novel in vitro AKU model allowed us to demonstrate the efficacy of the co-administration of NAC and ASC to counteract the negative effects of HGA for the treatment of ochronotic arthropathy.

BACKGROUND The current randomized, multicenter, Phase III trial was conducted to determine whether the disease free interval and overall survival of patients with T2–T4,N0–N3,M0 squamous cell carcinoma (SCC) of the oral cavity or oropharynx could be extended through the combination of surgery (and radiotherapy, if required) with perilymphatic recombinant IL-2 (rIL-2). METHODS Patients with a resectable T2–T4,N0–N3,M0 SCC of the oral cavity and oropharynx were assigned randomly to receive surgery and radiotherapy or to receive IL-2, surgery, and radiotherapy. Five thousand units of rIL-2 were injected around the ipsilateral cervical lymph node chain daily for 10 days before surgery. After surgery, contralateral 5-day rIL-2 courses were administered monthly for 1 year. The differences in disease free and overall survival between the two groups of patients were evaluated statistically. RESULTS Two hundred two patients finished the study. No significant complications related to rIL-2 were encountered, and surgery and radiotherapy were not hampered by its prior administration. Multivariate analysis conducted to determine the extent to which survival was influenced by rIL-2 and the other variables showed that rIL-2 significantly lengthened disease free survival (P < 0.01) and that this resulted in longer overall survival (P < 0.03). CONCLUSIONS The data emerging from this trial indicate that perilymphatic administration of low, nontoxic doses of rIL-2 is a simple and manageable way to delay recurrences of SCC. Cancer 2002;95:90–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10654

Chronic diseases pose a severe burden to modern National Health Systems. Individuals nowadays have a far more extended lifespan than in the past, but healthy living was only scantily extended. As much as longer life is desirable, it is saddened by chronic diseases and organ malfunctions. One contributor to these problems was recognized to be represented by microparticles (MPs). Our purpose is to better understand MPs, to contrast their ominous threat and possible clinical importance. For this intent we correlated MPs with thrombotic pathologies, hemophilia, malaria, diabetes, cardiovascular diseases, endothelial dysfunctions, pulmonary hypertension, ischemic stroke, pre-eclampsia, rheumatologic diseases-rheumatoid arthritis, polymyositis-dermatomyositis, angiogenesis and tumor progression-cancer; we listed the possibilities of using them to improve transfusion methods, as a marker for acute allograft rejection, in stem cell transplantation, as neuronal biomarkers, to understand gender-specific susceptibility for diseases and to improve vaccination methods and we presented some methods for the detection of MPs.

Alkaptonuria (AKU) is a rare genetic disease associated with deficient homogentisate 1,2-dioxygenase activity in the liver. This leads to the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues, which in turn become characterized by the presence of melanin-like pigments (ochronosis). Since at present, further studies are necessary to support the use of drugs for the treatment of AKU, we investigated the effects of various anti-oxidants in counteracting melanin-like pigmentation and oxidative stress related to HGA and its metabolites.We set up an in vitro model using human serum treated with 0.33 mM HGA and tested the anti-oxidants ascorbic acid, N-acetylcysteine, phytic acid (PHY), taurine (TAU), ferulic acid (FER) and lipoic acid (LIP) for their ability to prevent or delay the production of melanin-like pigments, as well as to reduce oxidative post-translational modifications of proteins. Monitoring of intrinsic fluorescence of HGA-induced melanin-like pigments was used to evaluate the efficacy of compounds.Our model allowed us to prove efficacy especially for PHY, TAU, LIP and FER in counteracting the production of HGA-induced melanin-like pigments and protein oxidation induced by HGA and its metabolites.Our model allows the opening of new anti-oxidant therapeutic strategies to treat alkaptonuric ochronosis.

Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver.

Dihydroxybenzoic acid (DHBA) derivatives of acetylsalicylic acid (ASA) are formed in vivo by the action of the hydroxyl radical (OH.). In order to evaluate the possible formation of OH(.) in acute myocardial infarction (AMI) in man, 9 consecutive patients with a first episode of AMI (8 males, 1 female, mean age 50.3 years), treated with rt-PA, and 8 healthy volunteers (7 males, 1 female, mean age 29.8 years) were studied. All subjects received 100 mg ASA p.o. daily; venous blood samples were taken 30 min after the first dose (time 0) and then at 3-, 6-, 12-, 24- and 48 h and 5 days. Serum was analyzed by HPLC and electrochemical detection for 2,3- and 2,5-DHBA contents. 2,3-DHBA was present in all subjects with AMI and undetectable in healthy volunteers at all time points studied. Serum levels of 2,5-DHBA did not show statistically significant differences between AMI patients and healthy volunteers. These data support the hypothesis that hydroxyl radicals are formed during AMI in man.

Background A systemic reaction to mycobacteria biases the balance of T helper cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some characteristics of mycobacterial infection. Children who have undergone tuberculin conversion after BCG vaccination seem to be more likely to lose their atopic symptoms. Inhibition of both allergic response and airway hyperreactivity after vaccination for mycobacteria has been observed in animal experiments. Objective To evaluate the effects that BCG vaccination has on the serological status of allergic people. Participants and Methods This study included 20 volunteers with a history of allergic rhinitis who were required to undergo BCG vaccination by Italian law. Epicutaneous allergy testing with a panel of common seasonal and perennial inhalational allergens and 2 blood withdrawals were performed. The serum total IgE levels and the serum allergen-specific IgE levels of each individual were measured just before BCG vaccination and again 4 months later. Total IgE levels were determined using the paper radioimmunosorbent test, and allergen-specific IgE levels were determined using the radioallergosorbent test. Results Total IgE and allergen-specific IgE levels were significantly decreased after BCG vaccination (P= .004 andP Conclusion BCG, an effective stimulus for cell-mediated immunity, deserves further study to evaluate its ability to modulate the immune response associated with allergic rhinitis.

A new de-N-acetylated glycosphingolipid termed WILD20, a breakdown product of GM1 obtained through alkaline hydrolysis, and characterized by nuclear magnetic resonance, mass spectrometry and elementary analysis, was found to inhibit phospholipase A2 via phosphokinase C translocation blockade. The substance inhibited various tumour cell lines in vitro, in synergy with doxorubicin and cisplatin. In vivo, it showed an antitumoral effect when both the tumour cells and WILD20 were injected at the same site (peritoneal cavity). Tumour cells, incubated with WILD20, showed a dose-dependent decrease of oncogenicity without impairment of viability. WILD20 also down-regulated tumour cell adherence to laminin and fibronectin. When peritumorally administered, WILD20 impaired tumour growth and potentiated the peritumoral effects of recombinant interleukin 2. The results obtained merit exploration of the therapeutical possibilities of this agent in human cancer patients.

We have identified 18 cases of functional pouch of the posterior rectal wall visualized by defecography. In the absence of previous evidence in the literature, we named this anomaly “posterior rectocele” and studied it from the clinical, radiologic, and endoscopic points of view.

The authors report eight cases of rectocele in male subjects studied with defecography and computed tomography. The pocket is located between the prostatic apex and the urogenital diaphragm. The abnormality has clinical significance.

Twenty patients with recurrent, inoperable head and neck squamous cell carcinoma received perilymphatic injections of natural interleukin-2 (nIL-2) for 10 days. Ten patients received 200 units (U) of nIL-2; five 1,000 U; and five 5,000 U. Irrespective of the location of the recurrence, the injections were always performed 1.5 cm below the insertion of the sternocleidomastoid muscle on the mastoid. When the ipsilateral lymphatic chain was still present, they were performed on the same side as the tumor site, whereas when it had been stripped as a result of previous surgery, they were contralateral. Patients who had undergone bilateral neck dissection were injected on the tumor side. Whenever possible, the treatment was repeated after 45-day intervals. In 13 patients (65%) with bilateral or contralateral lymph nodes, complete or partial disappearance of the lesion was observed. Despite these marked responses, the tumor always relapsed, and subsequent IL-2 courses were poorly effective. There were no systemic disturbances during or after treatment, but only moderate local swelling and pain.

Expression of immunocytochemically detectable markers in 100 cases of laryngeal carcinomas, homogeneous for staging and treatment, was correlated with clinical evolution of the disease. Follow-up for a minimum of 5 years was obtained in all cases. Paraffin sections were re-cut and stained in immunoperoxidase with monoclonal KL1, detecting medium-to-low molecular weight keratins, and with monoclonal HMFG2, revealing a surface glycoprotein. Expression of KL1-related antigen did not correlate with prognosis, whereas cases extensively positive for monoclonal HMFG2 (more than 50% cells stained) had a significantly better recurrence-free rate. In a group of tumors classified as Grade 3 (histologically poorly differentiated) and expressing a low degree of HMFG2-detectable surface glycoprotein (< 50 % cells stained), a high rate of recurrences (93%) was observed. This study indicates that the combined use of morphologic and biologic (immunohistochemical) criteria may constitute an independent parameter of primary importance in predicting the evolution of laryngeal carcinomas.

The production of leukocyte migration inhibition factor (LIF) from lymphocytes after stimulation with 3 M KCl soluble tumor and normal mucosa extracts was investigated in 30 patients with laryngeal carcinoma at different development stages and in 30 normal donors. The experiments were performed in heterologous and autologous systems. In heterologous systems 3 M KCl tumor extracts induced LIF production by heterologous lymphocytes from patients in 91 % of the cases, and normal mucosa extracts induced LIF production by heterologous lymphocytes from patients in 73 % of the cases and from normal donors in 90 % of the cases. In autologous systems 3 M KCl tumor extracts induced LIF production by autologous lymphocytes from the same patients in 65 % of the cases, whereas the normal laryngeal mucosa extracts induced LIF production by the same autologous lymphocytes in the 6 % of the cases. The high positivity percentage of the test in heterologous systems could be related to differences in the major histocompatibility complex. The 65 % test positivity in autologous systems using tumor extracts could be related to the presence of tumor associated antigens.

The specific tumor-induced LIF production in 30 laryngeal cancer patients has been investigated before and after the removal of adherent cells to evaluate the existence of a suppressor activity. LIF production, after challenging lymphocytes with 3 M KCl autologous tumor extracts, was significant in 16 patients and showed a further significant increase after removal of adherent cells. A conversion to significance when the adherent cells were removed was shown in 6 patients, with no previous significant LIF production. These data suggest the existence of a suppressor activity exerted by adherent cells on LIF production in laryngeal cancer patients.

Ten patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line purified by high pressure liquid chromatography for 10 days. Two hundred units of IL-2 in 0.5 ml were injected 1.5 cm from the insertion of the sternocleidomastoid muscle on the mastoid. When possible, courses were repeated at 45-day intervals. IL-2 was ineffective in two patients who had already undergone functional or radical neck dissection. By contrast, in six patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. The injections were occasionally followed by moderate local swelling and lymph node pain, but no systemic disturbances.

Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-γ). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-γ concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression.

The role of protein kinase C (PK-C) in the early metabolic events involved in human natural killer (NK) cell activation has been studied through the action of PK-C-specific activators and inhibitors. Highly purified human large granular lymphocytes (LGL) were treated for 1 hr with the diacylglycerol analog 1-oleoyl-2-acetyl glycerol (OAG) (10(-4)-10(-5) g/ml) or with 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-8)-10(-10) g/ml), both specific activators of PK-C. Both these agents consistently increased NK activity against K562 target cells. Suboptimal doses of either OAG or TPA also synergized with Ca2+ ionophores to augment spontaneous cytotoxic activity. Pretreatment of LGL with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrocloride (H7) (5-40 microM), a potent PK-C inhibitor, greatly reduced NK activity in a time- and dose-dependent fashion. By contrast, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA 1004), a potent cAMP- and cGMP-dependent PK inhibitor with almost no effect on PK-C, marginally reduced NK activity. Moreover, almost complete NK activity inhibition was observed when H7 (10 microM), but not HA 1004 (50 microM), was present in the NK assay. Finally, 48 hr stimulation of LGL with TPA (10(-6) g/ml), a treatment able to inactivate most of the PK-C cellular pool, almost completely abrogated NK activity. This functional evidence was supported by phosphorylation of several endogenous substrates which occurs within 5 min in TPA-treated LGL. Two proteins of 70 and 56 kDa have been identified as major PK-C substrates, together with other phosphorylated proteins with MW ranging from 177 to 43 kDa. H7, but not HA 1004, almost completely inhibited the TPA-induced phosphorylation of all of these proteins in the NK cells. These data strongly suggest that selective activation of PK-C plays an essential role in the mechanisms of NK cell activation.

SUMMARY The effect of gangliosides extracted from human group O Rh + erythrocytes on haemagglutination by BK virus was investigated. Experiments were performed on both ganglioside mixtures and isolated fractions separated by column chromatography and characterized by thin-layer chromatography. These results were compared with those obtained with standard preparations of gangliosides, and the inhibiting activity was shown to be confined mainly to gangliosides with a RF lower than GM1. It was also observed that the insertion of gangliosides in liposomes increased the haemagglutination-inhibiting activity and that ganglioside coating restored the ability of glycosidasetreated human red blood cells to agglutinate.

The specific tumor-induced leukocyte inhibition factor (LIF) production in laryngeal cancer patients has been investigated before and after the removal of adherent cells in order to evaluate the existence of a suppressor activity; 20 patients served as subject. The LIF production, after challenging the lymphocytes with 3MKC1 autologous tumor extracts, was significant in 12 patients and showed a further significant increase after the removal of adherent cells. In 3 patients with no previous significant LIF production, there was a conversion to significance when the adherent cells were removed. The other patients did not show any significant variation. These data seem to suggest the existence of a suppressor activity exerted by adherent cells in laryngeal cancer patients on LIF production.