HPV-related diseases in male patients: an underestimated conundrum.

PURPOSE: Human papillomavirus (HPV) infection is the most common sexually transmitted disease, in males and females worldwide. While the role of HPV in female diseases is well known and largely studied, males have negligibly been included in these programs, also because the proportion of women suffering and dying from HPV-related diseases is much larger than men. The aim of this review is to focus on HPV-related diseases in male patients. METHODS: We performed a literature analysis on the electronic database PubMed. We considered randomized trials, observational and retrospective studies, original articles having as topic the relationship between HPV male infection and the following items: oral, anal penile cancers, warts, condylomas, male infertility, altered sperm parameters, anti-sperm antibodies (ASA). We also included experimental in vitro studies focused on the effects of HPV infection on oocyte fertilization, blastocyst development, and trophoblastic cell invasiveness. In addition, studies describing the adjuvant administration of the HPV vaccination as a possible strategy to promote HPV clearance from semen in infected males were included. RESULTS: Regarding head and neck HPV-related diseases, the most important non-neoplastic disease is recurrent respiratory papillomatosis (RRP). Regarding neoplastic diseases, the proportion of head and neck cancers attributable to HPV has increased dramatically worldwide. In addition, nowadays, it is thought that half of head and neck squamous cell carcinomas (HNSCCs) cases in the United States are caused by infection with high-risk HPV. HPV is noteworthy in andrological practice too. It was described as having a high HPV prevalence, ranging between 50 and 70%, in male penile shaft, glans penis/coronal sulcus, semen as well as in scrotal, perianal, and anal regions. Moreover, in male patients, HPV infection has been associated, among other diseases, with penile cancers. HPV semen infection has been reported in about 10% in men from the general population and about 16% in men with unexplained infertility, although these data seem widely underestimated according to clinical experience. In particular, HPV semen infection seems to be most related to asthenozoospermia and to anti-sperm antibodies (ASAs). CONCLUSIONS: HPV infection represents a health problem with a detrimental social and public impact. Despite this evidence, little has been done to date to widely promote vaccination among young males.

Evaluation and comparison of automated hematology analyzer, flow cytometry, and digital morphology analyzer for monocyte counting.

INTRODUCTION: This study was aimed to evaluate monocyte counts on Sysmex XN-9000, Sysmex CyFlow Space System, and Sysmex DI60 and compare the performance of these systems with the reference optical microscopy (OM) assessment. METHODS: In all, 55 peripheral blood samples, collected in K3 EDTA tubes, were analyzed with XN-9000, CyFlow System (FlowDiff1 and 2), DI60, and OM. Within-run imprecision was carried out using normal samples. Data comparison was performed with Passing-Bablok regression and Bland-Altman plots. RESULTS: The within-run imprecision of monocyte count on XN, FlowDiff, OM, and DI60 ranged between 1.9% for FlowDiff 2 and 22.1% for DI60. The Passing-Bablok regression analysis of absolute count yielded slopes comprised between 0.93 (FlowDiff2 vs DI60) and 1.21 (DI60 vs OM), whereas the intercepts ranged between -0.002 (FlowDiff 1 vs FlowDiff 2) and 0.13 (FlowDiff1 and 2 vs DI60). Bland-Altman plots in absolute values yielded absolute bias comprised between -0.01 × 109 /L (FlowDiff 1 vs FlowDiff 2; DI60 vs OM) and 0.15 × 109 (XN-module vs DI60). CONCLUSION: The results of this analytical evaluation suggest that flow cytometry generates monocyte counts suitable for routine clinical use. OM or DI60 analysis may be useful for identifying morphologic abnormalities, but does not achieve a satisfactory level of accuracy for enumerating blood cells types such as monocytes, which are usually very low in peripheral blood.

Kidney transplantation process in Brazil represented in business process modeling notation.

Kidney transplantation is considered to be the best treatment for people with chronic kidney failure, because it improves the patients' quality of life and increases their length of survival compared with patients undergoing dialysis. The kidney transplantation process in Brazil is defined through laws, decrees, ordinances, and resolutions, but there is no visual representation of this process. The aim of this study was to analyze official documents to construct a representation of the kidney transplantation process in Brazil with the use of business process modeling notation (BPMN). The methodology for this study was based on an exploratory observational study, document analysis, and construction of process diagrams with the use of BPMN. Two rounds of validations by specialists were conducted. The result includes the kidney transplantation process in Brazil representation with the use of BPMN. We analyzed 2 digital documents that resulted in 2 processes with 45 total of activities and events, 6 organizations involved, and 6 different stages of the process. The constructed representation makes it easier to understand the rules for the business of kidney transplantation and can be used by the health care professionals involved in the various activities within this process. Construction of a representation with language appropriate for the Brazilian lay public is underway.

Psychopathology, emotional aspects and psychological counselling in infertility: a review.

Over the years, infertility has been variably defined. Infertility affects approximately 80 million people from all parts of the world. An important area of discussion has been represented by the possible causal link between psychopathology and infertility. In the past, the prevalence of psychiatric problems among infertile couples was estimated to be 25-60%. The incidence of depression and anxiety in infertile couples is significantly high than in fertile controls and in the general population respectively. Infertility has been linked to obsessive-compulsive symptoms, psychoticism, substance abuse and eating disorders. Psychological impact of infertility is greater in women than in men. Additionally, authors found that infertile patients were more alexithymic than healthy controls. In relation to the different needs, different psychological therapeutic interventions may be indicated. Psychological counseling can provide valuable assistance in dealing with infertility treatments and their eventual failures.

[The allergologic risk in food industry]. / Il rischio allergologico nell'industria agroalimentare.

The spectrum of occupational disease seen in the food industry mainly includes occupational asthma (and/or rhinitis), hypersensitivity pneumonitis and dermatitis. The differences between the Occupational Reactions to Food Allergens and Food Allergy are discussed.

Classification of postural profiles among mouth-breathing children by learning vector quantization.

BACKGROUND: Mouth breathing is a chronic syndrome that may bring about postural changes. Finding characteristic patterns of changes occurring in the complex musculoskeletal system of mouth-breathing children has been a challenge. Learning vector quantization (LVQ) is an artificial neural network model that can be applied for this purpose. OBJECTIVES: The aim of the present study was to apply LVQ to determine the characteristic postural profiles shown by mouth-breathing children, in order to further understand abnormal posture among mouth breathers. METHODS: Postural training data on 52 children (30 mouth breathers and 22 nose breathers) and postural validation data on 32 children (22 mouth breathers and 10 nose breathers) were used. The performance of LVQ and other classification models was compared in relation to self-organizing maps, back-propagation applied to multilayer perceptrons, Bayesian networks, naive Bayes, J48 decision trees, k, and k-nearest-neighbor classifiers. Classifier accuracy was assessed by means of leave-one-out cross-validation, area under ROC curve (AUC), and inter-rater agreement (Kappa statistics). RESULTS: By using the LVQ model, five postural profiles for mouth-breathing children could be determined. LVQ showed satisfactory results for mouth-breathing and nose-breathing classification: sensitivity and specificity rates of 0.90 and 0.95, respectively, when using the training dataset, and 0.95 and 0.90, respectively, when using the validation dataset. CONCLUSIONS: The five postural profiles for mouth-breathing children suggested by LVQ were incorporated into application software for classifying the severity of mouth breathers' abnormal posture.

Maize food allergy: a double-blind placebo-controlled study.

BACKGROUND: Maize allergy is not very common especially in Europe. The number of studies that address IgE mediated maize allergy is all too few. OBJECTIVE: Evaluate subjects with a history of maize allergy by double-blind, placebo-controlled food challenge; identify the spectrum of symptoms manifested during challenge; determine the lowest provocation dose (PD) during challenge; determine the performance characteristics of maize skin prick test and specific IgE. METHODS: Twenty-seven patients with a history of maize allergy were enrolled to be evaluated by skin test, specific IgE and double-blind placebo-controlled maize challenge. RESULTS: Forty-eight percent of the patients were challenge positive. PD range was 0.1-25 g. Fifty-four percent of the maize allergic subjects had a PD that was < or = 2.5 g; two subjects reacted to 100 mg of maize. Comparison of maize specific IgE levels and skin test results to the challenge results revealed the following (specific IgE level/skin testing): sensitivity 1.00/0.846, specificity 0.077/0.384, positive predictive value 0.520/0.579, and negative predictive value 1.00/0.714. CONCLUSION: Maize is a cause of IgE-mediated allergic reactions to foods in adults and children. Nearly half of the subjects recruited were confirmed by challenge to be allergic to maize. Twenty-three percent of the positive challenge patients manifested symptoms that involved two organ systems, thus fulfilling the criteria for maize induced anaphylaxis. Maize is allergenic and can pose a risk for symptomatic food allergy at a dose of 100 mg.

The role of health technology assessment in the comprehensive evaluation of the impact of immunotherapy on real practice.

The increasing development of new health care technologies, along with the ageing of the population and the increasing patients' expectations, cause a significant raise in medical costs, inducing in policy makers the need for well-funded information to support their decisions. The development of Health Technology Assessment (HTA), which is the systematic evaluation of properties, effects or other impacts of health technology and can be considered as a bridge between the world of research and the world of policy-making, reflects this high level of demand. HTA requires a multidisciplinary approach, that covers many different disciplines, in order to assess various aspects of health technologies, as technical properties, safety, efficacy/effectiveness, economic aspects, social, legal, ethical and political impacts. Allergic diseases show a worldwide increasing prevalence and consequent increasing costs, which result very high in recent evaluations. Specific immunotherapy is the only treatment able to alter, differently from drugs, the natural course of allergic diseases, exerting a long-lasting therapeutic effect, that persists also after stopping the therapy. This has a potential great impact in the cost of disease, which only recently was considered in properly designed studies. These issues claim for a larger use of HTA, which may provide a more comprehensive approach to the evaluation of the impact of immunotherapy on allergic patients.

Pharmacoeconomics of subcutaneous allergen immunotherapy.

The current burden of allergic diseases, estimated by both direct and indirect costs, is very relevant. In fact the cost estimation for rhinitis amount globally to 4-10 billion dollars/year in the U.S. and to an average annual cost of 1089 euros per child/adolescent and 1543 euros per adult in Europe. The estimated annual costs in Northern America for asthma amounted to 14 billion dollars. Consequently, preventive strategies aimed at reducing the clinical severity of allergy are potentially able to reduce its costs. Among them, specific immunotherapy (SIT) joins to the preventive capacity the carryover effect once treatment is discontinued. A number of studies, mainly conducted in the US and Germany demonstrated a favourable cost-benefit balance. In the nineties, most surveys on patients with allergic rhinitis and asthma reported significant reductions of the direct and indirect costs in subjects treated with SIT compared to those treated with symptomatic drugs. This is fully confirmed in recent studies conducted in European countries: in Denmark the direct cost per patient/year of the standard care was more than halved following SIT; in Italy a study on Parietaria allergic patients demonstrated a significant difference in favor of SIT plus drug treatment for three years versus drug treatment alone, with a cost reduction starting from the 2nd year and increasing to 48% at the 3rd year, with a highly statistical significance which was maintained up to the 6th year, i.e. 3 years after stopping immunotherapy, corresponding to a net saving for each patient at the final evaluation of 623 euros per year; in France a cost/efficacy analysis comparing SIT and current symptomatic treatment in adults and children with dust mite and pollen allergy showed remarkable savings with SIT for both allergies in adults and children.

Economic evaluation of sublingual immunotherapy: an analysis of literature.

Allergic rhinitis and asthma constitute a global health problem because of their very high prevalence and the consequent burden of disease, concerning medical and economical issues. Among the treatments of allergy, specific immunotherapy has the capacity to favourably alter the natural history of the disease both during and after its performance and thus to reduce the direct and indirect costs of allergic rhinitis and asthma. A number of studies reported such cost reduction for traditional, subcutaneous immunotherapy and recent data demonstrate that also sublingual immunotherapy (SLIT) is associated to economic advantages and/or monetary savings, specifically in terms of reduction of disease economic burden. Only few formal economic assessments of SLIT have been carried out so far, this article will present and discuss the published studies addressed to this issue. The data obtained, although the number of studies is still limited, provide preliminary evidence supporting a SLIT effect on sparing costs for respiratory allergy.

Practice parameters for sublingual immunotherapy.

The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, meta-analysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre co-seasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient's tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).

Screening the allergenic repertoires of wheat and maize with sera from double-blind, placebo-controlled food challenge positive patients.

BACKGROUND: Food allergy to wheat and maize is an increasing factor of deterioration of life quality, especially childhood and can, in rare cases, even induce anaphylaxis. Although omega-5 gliadin from wheat and maize lipid transfer protein have been characterized as major cereal allergens on the molecular level, the list of food allergens is far to be complete. METHODS: To identify the IgE-binding repertoires of wheat and maize we screened respective cDNA libraries displayed on phage surface with sera from patients with a confirmed food allergy. The study included six patients with a positive double-blind, placebo-controlled food challenge (DBPCFC) to wheat, nine patients with a positive DBPCFC to maize, and six patients with anaphylactic reactions after ingestion of wheat. RESULTS: The enriched sequences encoding IgE-binding proteins showed heterogeneous repertoires for both, wheat and maize. The selected wheat repertoire yielded 12, the maize repertoire 11 open reading frames. Among these we identified allergens belonging to already characterized allergens families, such as gliadin, profilin and beta-expansin. Besides, we found novel proteins with high cross-reactive potential, such as thioredoxins, as well as sequences that had so far not been related to cereal allergy at all. The IgE-binding capacity of some selected proteins was evaluated in vitro and cross-reactivity was demonstrated by competition ELISA. CONCLUSION: With regard to the heterogeneity of the characterized sequences as well as to the biochemical nature of the new allergens detected we conclude that wheat and maize-related food allergy is more complex than so far anticipated.

Cost effectiveness of sublingual immunotherapy in children with allergic rhinitis and asthma.

BACKGROUND: Economic evaluations are increasingly relevant in order to provide support for decision makers when judging about alternative ways to allocate public funds. Aim of this study was to evaluate the economic effect of treatment with high dose sublingual immunotherapy (SLIT) in children. METHODS: The study involved one allergy center, located in the north of Milan, Italy. From the existing records of patients seen for allergic disease, we extracted all children and adolescents with allergic disease, who had 1-year data prior to receiving SLIT and 3-year data on SLIT. Outcome measures (number of exacerbations, visits, absence from nursery or school), direct costs (euros spent on drugs, specialist visits, SLIT) and indirect costs (costs resulting from children school and parental work loss) were analysed. A second analysis compared a sub-group of allergic asthmatic children with a control group for costs, based on records of patients not SLIT-treated, extracted from a network-database of paediatricians. RESULTS: 135 patients were extracted, of which 46 had perennial, and 89 had seasonal allergy with comparable gender and age distribution. A substantial reduction was found in all outcome measures during SLIT compared with the before period. The average annual cost/patient was 2672 before SLIT initiation and _629/year during SLIT. Similar results were found for allergen subgroups. The asthma sub-analysis involved 41 children with SLIT and 35 controls. Again, SLIT patients showed a substantial reduction in outcome measures; the direct cost/patient over the whole follow-up (4 years) was _1182 for SLIT patients and _1100 for controls. CONCLUSION: High dose SLIT may be effective in reducing the cost of allergic rhinitis and asthma and comparably expensive to conventional treatment in children with allergic asthma over a 4 years follow-up.

Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study.

BACKGROUND: The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. OBJECTIVE: We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. METHODS: Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. RESULTS: Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002). CONCLUSION: Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia.

Identification and characterisation of the IgE-binding proteins 2S albumin and conglutin gamma in almond (Prunus dulcis) seeds.

BACKGROUND: Almond proteins can cause severe anaphylactic reactions in susceptible individuals. The aim of this study was the identification of IgE-binding proteins in almonds and the characterisation of these proteins by N-terminal sequencing. METHODS: Five sera were selected from individuals with a positive reaction to food challenge. Sodium dodecylsulphate-polyacrylamide gel electrophoresis and immunoblotting were performed on almond seed proteins. Purified IgE-binding proteins were tested for immunoblot inhibition with sera pre-incubated with extracts of hazelnut and walnut. RESULTS: N-terminal sequences of the 12-, 30- and 45-kD proteins were obtained. The 45- and 30-kD proteins shared the same N terminus, with 60% homology to the conglutin gamma heavy chain from lupine seed (Lupinus albus) and to basic 7S globulin from soybean (Glycine max). The sequences of the N-terminal 12-kD protein and of an internal peptide obtained by endoproteinase digestion showed good homology to 2S albumin from English walnut (Jug r 1). Immunoblot inhibition experiments were performed and IgE binding to almond 2S albumin and conglutin gamma was detected in the presence of cross-reacting walnut or hazelnut antigens. CONCLUSIONS: Two IgE-binding almond proteins were N-terminally sequenced and identified as almond 2S albumin and conglutin gamma. Localisation and conservation of IgE binding in a 6-kD peptide obtained by endoproteinase digestion of 2S albumin was shown.

Metastatic metanephric adenoma with foci of papillary carcinoma in a child: a combined histologic, immunohistochemical, and FISH study.

We report an example of metastatic metanephric adenoma containing foci of papillary carcinoma in the primitive tumor arising in the left kidney of an 11-year-old girl. Histology revealed a monomorphous population of small cells with bland cytology arranged in pseudoglandular, tubular, papillary, and glomeruloid structures with frequent psammoma bodies. Intermixed there were foci of and small cavities lined by larger cells with eosinophilic cytoplasm and larger nuclei with small nucleoli. A regional lymph node contained metastatic deposits with the former histologic pattern. By immunohistochemistry the small cells were negative for carcinoembryonic antigen (CEA) and keratin 7 while these antibodies reacted positively in the larger cells. A fluorescent in-situ hybridization (FISH) study for chromosome 17 in imprints from the primitive tumor revealed 3 signals in about 10% of the nuclei while the rest was disomic. Disaggregated cells from the metastatic lymph node consistently revealed 2 signals for chromosomes 7, 16, and l7. Histology of the primitive tumor resembled the epithelial component of the so-called metanephric adenofibroma while the metastatic lymph node exhibited histologic and FISH genomic features of metanephic adenoma. Int J Surg Pathol 9(3):241-247, 2001

Determination of the primary structure of two lipid transfer proteins from apricot (Prunus armeniaca).

It has been recently demonstrated that the major allergen of apricot is a protein of molecular mass (Mr) 9000 belonging to the family of Lipid Transfer Protein. The aim of this study was the determination of the primary structure of apricot LTP by micro-sequencing and mass spectrometric analyses. Apricot LTP is a 91 amino acids protein like peach and almond LTPs with a sequence identity of 91% and 94%, respectively. Like for the peach LTP, out of the 25 amino acids forming the inner surface of the tunnel-like hydrophobic cavity in maize ns-LTP, 16 are identical and 7 similar in the apricot LTP, supporting the hypothesis of a similar function.

The major allergen of sesame seeds (Sesamum indicum) is a 2S albumin.

BACKGROUND: Allergic reactions induced by ingestion of foods containing sesame seeds are a well recognized cause of severe food-induced anaphylaxis. OBJECTIVE: This study aimed to identify and characterize the clinically most important major allergen of sesame seeds. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and IgE immunoblotting were performed on sera of 10 patients selected for severe and documented allergic reaction after eating food containing sesame. The major allergen was purified by gel filtration and characterized by isoelectric point (pI), glycosylation and amino acid sequencing. RESULTS: All the patients had positive IgE antibodies and skin prick tests (SPTs) to sesame. The major, clinically most important allergen was a protein with molecular mass of about 9000. It was not glycosylated, the amino acid sequence showed it was a 2S albumin with a pI of 7.3; the small and the large subunits, forming the whole protein, showed pI values of 6.5 and 6.0.

Characterization of the major allergen of plum as a lipid transfer protein.

BACKGROUND: Allergy to Prunoideae fruit (plum, peach, cherry and apricot) is one of the most frequent food allergies in southern Europe. All these fruits cross-react in vivo and in vitro, as they share their major allergen, a 9 kD lipid transfer protein (LTP). OBJECTIVE: The aim of the study was the identification and molecular characterization of the major allergen of plum. METHODS: The IgE pattern of reactivity to plums was investigated by SDS-PAGE and immunoblotting with the sera of 23 patients. The identified major allergen was purified by HPLC, using a cationic-exchange column followed by gel-filtration. Further characterization was achieved by periodic-Schiff stain, isoelectrofocusing and N-terminal amino acid sequencing. RESULTS AND CONCLUSIONS: The major allergen of plum is a 9 kD lipid transfer protein, not glycosylated and with a basic character (pI>9), highly homologous to the major allergen of peach.