Review article: intestinal lymphoid nodular hyperplasia in children--the relationship to food hypersensitivity.

BACKGROUND: Lymphoid aggregates are normally found throughout the small and large intestine. Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered 'physiological'. In children presenting with gastrointestinal symptoms the number and size of the lymphoid follicles are increased. Patients suffering from gastrointestinal symptoms (i.e. recurrent abdominal pain) should systematically undergo gastroduodenoscopy and colonoscopy. With these indications LNH, especially of the upper but also of the lower gastrointestinal tract has been diagnosed, and in some children it may reflect a food hypersensitivity (FH) condition. AIM: To review the literature about the relationship between LNH and FH, particularly focusing on the diagnostic work-up for LNH related to FH. METHODS: We reviewed literature using Pubmed and Medline, with the search terms 'lymphoid nodular hyperplasia', 'food hypersensitivity', 'food allergy' and 'food intolerance'. We overall examined 10 studies in detail, selecting articles about the prevalence of LNH in FH patients and of FH in LNH patients. RESULTS: Collected data showed a median of 49% (range 32-67%) LNH in FH patients and a median of 66% (range 42-90%) FH in LNH patients. Literature review pointed out that the most important symptom connected with LNH and/or FH was recurrent abdominal pain, followed by diarrhoea and growth retardation. Both LNH and FH are associated with an increase in lamina propria γ/δ+ T cells, but the mechanisms by which enhanced local immune responses causing gastrointestinal symptoms still remain obscure. CONCLUSIONS: When assessing FH, we rely on clinical evaluation, including elimination diet and challenge tests, and endoscopic and immunohistochemical findings. Considering the possible co-existence of duodenal and ileo-colonic LNH, upper endoscopy can be recommended in children with suspected FH, especially in those presenting with additional upper abdominal symptoms (i.e. vomiting). Likewise, lower endoscopy might be additionally performed in patients with suspected FH and LNH of the duodenal bulb, also presenting with lower abdominal symptoms (i.e. recurrent abdominal pain).

Low-grade fever: how to distinguish organic from non-organic forms.

BACKGROUND AND AIM: Low-grade fever (LGF) is defined as a body temperature between 37.5 and 38.3 degrees C, which is below the classical value reported for fever of unknown origin (FUO). We attempted to characterise its epidemiology, aetiology and clinical aspects to improve the methodological approach to diagnosis. DESIGN AND METHODS: We reviewed and evaluated a survey of patients with LGF, followed as outpatients of our Department, a tertiary referral centre from 1997 to 2008. The same classifications were applied for classical FUO, and in the patients diagnosed with LGF, we also investigated for habitual hyperthermia (HH). RESULTS: Seventy-three patients were selected and divided into two groups: group A included 32 patients classified with organic fever and group B included 41 patients with HH. Aetiology of organic LGF was: infectious disease 59%; neoplasm 3.1%; inflammatory non-infectious disease 6.2%; miscellaneous 18.7%; undiagnosed 12.5%. Mean age was significantly higher in the organic fever than in the HH group (p < 0.02). Splenomegaly and loss of weight were significantly associated with organic fever (p < 0.05), while dizziness and general malaise were associated with HH. Lack of any pathological signs at physical examination was significantly more frequent in HH (p < 0.0001). Among the biochemical tests, white blood cells and C-reactive protein were more frequently above normal limits in group A than in group B (p < 0.05). CONCLUSIONS: In our experience, LGF requires the same methodological diagnostic approach as FUO, because there is no relationship between body temperature values and the severity of the underlying diseases, and the aetiological spectrum is also the same.

Clinical importance of eosinophil count in nasal fluid in patients with allergic and non-allergic rhinitis.

Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNF's accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNF's median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNF's median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNF's median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNF's median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was < or = 5.0, AUC = 0.94. ECNF's median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was < or = 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNF's performance was moderately accurate in distinguish patients with AR and NAR.

Risk factors, atrial fibrillation and thromboembolic events.

AIM: The aim of this study was to evaluate the relation between risk factors for atrial fibrillation (AF) and thromboembolic complications. METHODS: We studied 480 patients (mean age: 71.2+/-11.6 years): 240 with paroxysmal AF, 240 with permanent AF. The association between AF and the presence of risk factors, cardiac and systemic disease was observed and the correlation with the occurrence of complications analyzed. RESULTS: Patients with AF had a high prevalence of the following conditions: hypertension, hypertensive heart disease (HHD), coronary artery disease, hyperthyroidism. Thromboembolism was observed in 26.6% of the patients. A correlation between the occurrence of a thromboembolic complication and the presence of one of the following risk factors for thromboembolism was observed: older age, diabetes mellitus, HHD and hyperfibrinogenemia. No correlation was detected between: female sex, arterial hypertension, hypercholesterolemia, smoking, and obesity. Exitus was observed in 7 patients with permanent AF. CONCLUSION: Older age, diabetes mellitus, HHD and hyperfibrinogenemia were strongly associated with the occurrence of thromboembolic complications. Patients with effectively pharmacologically controlled hypertension had not more frequently thromboembolic complications. A strict blood pressure control may prevent thromboembolic complications of AF.

Immunology of human rickettsial diseases.

Among human rickettsial diseases caused by micro-organisms of the genus Rickettsia (Order Rickettsiales; Family Rickettsiaceae), transmitted to human hosts through arthropod vectors, Mediterranean Spotted Fever, or Boutonneuse Fever, and Rocky Mountain Spotted Fever are considered to be important infectious diseases due to continued prevalence in the developed world, and potentially fatal outcome in severe cases. Proliferation of rickettsiae, at the site of the tick bite, results in focal epidermal and dermal necrosis (tache noire). Rickettsiae then spread via lymphatic vessels to the regional lymph nodes, and, via the bloodstream, to skin, brain, lungs, heart, liver, spleen and kidneys. The pathogen invades and proliferates in the endothelial cells of small vessels, target cells of rickettsial infection, destroying them, and spreading the infection to the endothelia of the vascular tree. The damage of the endothelium, and the subsequent endothelia dysfunction, is followed by the activation of acute phase responses, with alteration in the coagulation and in the cytokine network, together with a transient immune dysregulation, characterized by the reduction in peripheral CD4+ T lymphocytes.

Immunopathology of leishmaniasis: an update.

Leishmaniasis represents a severe, increasing, public health problem. The perspective of its control is highly dependent on research progress, on therapeutic manipulations of the immune system, and on vaccine development. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-1 response and IFN-gamma production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. IL-4 and IL-13 (TH2 cytokines) can promote disease progression in cutaneous leishmaniasis, whereas IL-4 would appear to enhance protective type-1 responses in visceral leishmaniasis. Thus, the TH1/TH2 paradigm of resistance/susceptibility to intracellular parasites is probably an oversimplification of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of antigen specific regulatory T cell subsets may provide an environment that contributes to the balance between TH1 and TH2 cells. Finally, the involvement of CD8 positive T cells has been described, but the modality of their function in this kind of infection has not been so far elucidated.

Therapeutic patient education in oncology: pedagogical notions for women's health and prevention.

Therapeutic patient education has been defined by the World Health Organization as a comprehensive approach to support patients and their families to better understanding of their diseases. In oncology, the contribution of therapeutic education may enable the patients to have adequate information of the illness, to actively participate in the management of the disease, to understand how to live with the illness, to learn how to face the critical moments of the clinical course, and to live in harmony with all health professionals. In addition, there may be several advantages for health professionals: a reduction in emotional labour, increased professional satisfaction, and a reduction in the potential tensions and conflicts with patients and their relatives. We suggest that therapeutic patient education in oncology may be useful for both patients and health professionals and probably lead to a reduction in the costs of healthcare delivery.

Relationship between specific serum IgE to Ascaris lumbricoides and onset of respiratory symptoms in Bangladesh immigrants.

The role of helminths in asthma and/or rhinitis and in allergic sensitization is still unclear. We assessed the relationship between Ascaris-specific IgE, respiratory symptoms and allergic sensitization in Bangladesh immigrants. 246 individuals were examined from 1996 to 2001. Serum total IgE, Ascaris IgE, specific IgE to inhalant allergens, skin prick tests (SPT) and parasitological evaluation of the stool were performed. Total serum IgE were significantly higher in Ascaris-IgE positive (> 0.35 kU/L) individuals (806.5 [409.0-1436.0] kU/L vs. 207.0 [127.0-332.5] kU/L; P < 0.0001) and in subjects with respiratory symptoms (413.0 [239.0-1096.0] kU/L vs. 259.5 [147.0-387.0] kU/L), (P < 0.0001), but not in SPT positive subjects (413.0 [179.0-894.0] kU/L vs. 404.6 [305.0-1201.0] kU/L (P = 0.5). Ascaris-specific IgE were detected in 48 subjects with respiratory symptoms (40.0%) and in 46 subjects without respiratory symptoms (36.5%) (P = 0.5). The SPT positivity was similar between Ascaris-IgE seropositive (38.2%) and Ascaris-IgE seronegative (38.1%) subjects (P = 0.9). Total IgE and length of stay in Italy correlated with SPT positivity (OR 5.6 [CI 95% 1.5-19.8], P = 0.007, and OR 1.5 [CI 95% 1.3-1.7], P< 0.0001), and with respiratory symptoms (OR 13.7 [CI 95% 3.0-62.4];, P = 0.0007, and OR 2.4 [CI 95% 1.9-3.0], P < 0.0001). Ascaris-IgE were negatively associated with SPT positivity (OR 0.3 [CI 95% 0.1-0.8], P = 0.02) and with respiratory symptoms (OR 0.1 [CI 95% 0.04-0.7], P = 0.01). Our findings favour the role of environmental factors in the development of respiratory symptoms in immigrants, irrespective of Ascaris-IgE.

Is there a role for antileukotrienes in urticaria?

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, i.e. leukotriene receptor antagonists and synthesis inhibitors, are a new class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma. We searched the MedLine database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin or food additive hypersensitivity or with autoreactivity to intradermal serum injection when taken with an antihistamine but not in moderate chronic idiopathic urticaria. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angio-oedema, and exercise-induced anaphylaxis.

Role of TLR4 receptor polymorphisms in Boutonneuse fever.

The genetics of the interaction between host and microbes plays an essential role in the survival of the individual and attainment of longevity. The activation of toll-like receptor (TLR)4 plays a key role in natural and clonotypic immune responses. We evaluated whether TLR4 genotype is a component of genetic background protective versus rickettsiosis and whether this background influences longevity. We genotyped for +896A/G TLR4 polymorphism 78 patients affected with Boutonneuse fever, 78 age-matched controls and 78 advanced age individuals from Sicily. The +869G allele, that attenuates receptor signalling, was significantly overrepresented in patients in comparison with age-matched controls. By analyzing data according to gender, this allele was significantly higher in female patients when compared to advanced age women. Pro-inflammatory responses are programmed to resist fatal infections. So, it is not surprising that the genetic background of people that survive to an advanced age may be protective against infections. However, this seems to occur in women but not in men. In a previous study, the +896G TLR4 allele was overrepresented in advanced age men and underrepresented in men affected by myocardial infarction. Thus, previous and present results tend to agree with the suggestion that men and women may follow different trajectories to reach longevity. For men it might be more important to control atherogenesis, whereas for women it might be more important to control infectious diseases.

Determinants of bronchial hyperresponsiveness in subjects with rhinitis.

Subjects with rhinitis but without asthma may have coexisting bronchial hyperresponsiveness, although the reasons for this are uncertain. To evaluate the factors that determine BHR in rhinitis we examined 410 patients with symptomatic rhinitis with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)>or=80% of the predicted value. In all subjects a skin prick test (SPT) was performed, a determination of total serum IgE and an eosinophils count in the blood. Of the 410 subjects we found that 161 (39.3%) exhibited a methacholine PD20 of 800 mg or less (Group A), whereas 249 (60.7%) had a methacholine PD20 more of 800 mg (Group B). Despite the matched mean values for FEV1 and FVC, compared with Group B, Group A had a lower predicted forced expiratory flow between 25% and 75%(FEF25%-75%) (86.7 +/- 12.0 vs. 93.7 +/- 7.3, P < 0.0001). A great portion of the subjects of the Group Ain respect to subjects of the Group B were exposed to passive smoke (37.8% vs. 22.0%, P = 0.0008), reported having mothers with asthma (34.1% vs. 6.0%, P < 0.0001), presented a positive skin prick test (93.7% vs. 67.0%, P < 0.0001), had higher levels of total serum IgE (geometric mean of Log10 2.46 +/- 0.27 kU/L vs. 2.06 +/- 0.38 kU/L, P < 0.0001) and higher blood eosinophil counts (geometric mean of Log10 2.67 +/- 0.07 x 10(-3) mL vs. 2.57 +/- 0.09 x 10(-3) mL, P < 0.0001), and reported increased nasal obstruction (2.0 (95% CI 1.8 to 2.2) vs. 0.6 (95% CI 0.5 to 0.7), P < 0.0001). Logistic regression demonstrates that nasal obstruction (OR 2.19, 95% CI 1.72 to 2.80) and the presence of positive SPT (OR 6.15, 95% CI 2.42 to 15.61) were the most available predictors to discriminate between subjects with BHR and subjects without BHR. In addition, BHR was positively related to blood eosinophil counts (OR= 2.80, 95% CI 1.54 to 5.07), FEF25%-75% values (OR= 2.72, 95% CI 1.23 to 5.99) and familiarity (mother) for asthma (OR = 2.45, 95% CI 1.10 to 5.46). Whereas passive smoke and total serum IgE were not positively related to BHR. Increased nasal obstruction and the presence of positive SPT were the most available predictors to discriminate between subjects with and without BHR. Finally, BHR was positively related to blood eosinophil counts, FEF25%-75% values and to familiarity (mother) for asthma.

Evaluation of an IgM-ELISA test for the diagnosis of human leptospirosis.

Leptospirosis is a zoonosis with a worldwide distribution very common in most countries. In Italy this acute febrile illness is more frequent in the Northern than in the Southern regions. In the period 1994-1996, the number of cases of Leptospirosis in Sicily was lower with respect to the northern-central regions (7.2% and 73.4% respectively). Between January 1990 and December 1999, a total of 9 leptospirosis cases were observed in the Regional Centre for Leptospirosis of Palermo. The patients were all males (age between 22 and 59 years) and their occupations varied. Laboratory diagnosis is performed by the classical microagglutination microscopical (MAT) but this test is very complex and time-consuming. This study compared the classical MAT with ELISA IgM by using 19 serum samples from 9 patients with confirmed leptospirosis. We also tested 23 serum samples from blood-donors and 29 serum samples from patients with other infectious diseases. By the MAT and the PanBio IgM ELISA all sera from patients were found to be positive. Our results indicate that MAT represents the test with the highest degree of specificity (100%), but ELISA is simpler to perform, considering the favourable degree of sensitivity (100%) and specificity (95.9%).

Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study.

BACKGROUND: Atopic dermatitis (AD) is a chronic allergic inflammatory disease, which manifests itself with eczematous skin lesions. OBJECTIVE: We compared the clinical efficacy of tacrolimus ointment (0.1%) given twice a day and oral cyclosporine (3 mg/kg) given once daily. Rescue medication for itching included cetirizine 10-20 mg (equal to one or two tables). METHODS: Thirty patients, aged 13-45 years (mean+/-SD 27.1+/-10.9), with a history of moderate-to-severe AD were randomized to treatments, 15 patients for each treatments. Assessment of efficacy was based on SCORAD, on scores of daily itching, erythema, interference with sleep, due to the skin condition and days without use of cetirizine tablets. SCORAD, measured on a scale (0-103), was evaluated before treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment. Similarly, the means of daily symptoms, on a scale (0-3), were evaluated before the treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment; finally, on day without use of cetirizine tablets. The safety of the study treatments was assessed through haematologic, biochemical and urinary testing and on systolic and diastolic blood pressures and heart rate measurements. RESULTS: SCORAD decreased in the two treatment groups 14 days after the beginning of the period study. However, the patients in tacrolimus ointment group reported significantly lower SCORAD than those treated with oral cyclosporine. Overall SCORAD, as assessed by the area under the curve (AUC) day(0-42) (score/day), was significantly lower in the tacrolimus ointment group when compared with oral cyclosporine (P<0.001). Similarly, AUC day(0-42) (score/day) for itching, erythema and number of nights without interference with the sleep due to skin condition were significantly lower in the group of patients treated with tacrolimus compared with those treated with cyclosporine (P=0.003, 0.005 and 0.01, respectively). As regards the use of rescue medication, expressed by median of number of days without use of anti-H(1), it was significantly lower in the group treated with tacrolimus (82.5) than in the cyclosporine group (76.5) (P=0.03). There were no appreciable changes in haematological and biochemical indices, in both treatments groups. CONCLUSION: The results of this comparative study demonstrate that tacrolimus ointment twice daily and cyclosporine administered orally once daily are effective on SCORAD, daily symptoms and anti-H(1) rescue. When we compared tacrolimus and cyclosporine there was a faster onset of action in the group treated with tacrolimus. The two drugs presented the same safety. However, these data support the preferential use of topical tacrolimus 0.1% in AD, because cyclosporine has potential side-effects.

Rickettsial disease: classical and modern aspects.

Rickettsial diseases have been reassessed in recent years since they represent an important field in today's medicine. New agents have been described: some are non-pathogenic agents and the others are associated with well-defined or peculiar clinical patterns. In addition, different species of rickettsiosis are found in relation to the geographic areas of the world. Some agents may be defined as variants of older diseases whereas most of the newly described forms of rickettsiosis represent distinct entities with unique epidemiologial and clinical features. Probably the main news regards the group of the spotted fevers. An additional new aspect is linked to the medicine of travellers and tourists. However, this aspect may not be significant for the rickettsial diseases in relation to other human illnesses, such as malaria. Therefore, an investigation into the geographical origin of patients has to enter our routine medical work.

Monosodium benzoate hypersensitivity in subjects with persistent rhinitis.

BACKGROUND: Very few data are available from the literature on whether nonatopic subjects affected by persistent rhinitis may show the appearance of objective symptoms of rhinitis after the ingestion of food additives such as tartrazine (E102), erythrosine (E127), monosodium benzoate (E211), p-hydroxybenzoate (E218), sodium metabisulphite (E223), and monosodium glutamate (E620). It is still unclear whether the ingestion of food additive may cause, as well, a consensual reduction of nasal peak inspiratory flow (NPIFR). Therefore, we used a double-blind placebo-controlled (DBPC) study to evaluate this hypothesis. PATIENTS AND METHODS: Two hundred and twenty-six consecutive patients (76 males and 150 females) aged 12-60 years (mean age 40.2 +/- 16.3 years). After 1 month of an additive-free diet regimen, an open challenge was carried out (food additive-rich diet for 2 weeks). After this period, challenges were administered in a DBPC manner using the above-mentioned substances under investigation. RESULTS: Twenty of 226 subjects (8.8%) reported an improvement of the symptoms of rhinitis after additive-free diet. More precisely, six of 226 (2.6%) were symptom-free and 14 of 226 (6.2%) showed an improvement in their symptoms after an additive-free diet. As far as the results for DBPC are concerned, 20 challenges with monosodium benzoate induced both objective (i.e. sneezing and rhinorrhoea) and subjective symptoms (nasal blockage and nasal itching) of rhinitis with reduction of NPIFR >/=20%, 45 challenges induced subjective symptoms of rhinitis (i.e. nasal blockage and nasal itching), without reduction of NPIFR >/=20% of the basal value, two with tartrazine, seven with erythrosine, 19 with monosodium benzoate, three with p-hydroxybenzoate, six with sodium metabisulphite, and eight with monosodium glutamate, respectively. CONCLUSIONS: The observation that nonatopic persistent rhinitis may be caused by the frequent, probably daily, ingestion of small doses of a nontolerated substance is intriguing and suggests that at least some patients with 'chronic vasomotor rhinitis' may be intolerant to a particular food additive. Therefore, food additives can be considered triggers or aggravating factors, rather than aetiological factors.

Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis.

BACKGROUND: Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms. OBJECTIVE: We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. METHODS: One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. RESULTS: All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. CONCLUSION: The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.

Statins and osteoporosis: myth or reality?

Several beneficial effects produced by statins over and above the reduction in plasma cholesterol levels, the so-called ''pleiotropic effects'' of statins, have been described. Recent clinical and experimental data have suggested a potential new effect of these drugs, namely a reduction in the risk of osteoporotic fractures. In 1999 the role of statins in bone formation was shown and, after that, observations of large groups of patients have pointed to a reduction in the risk of osteoporotic fractures with the use of statins compared to those using other lipid-lowering drugs or to the control group. The first prospective studies have produced contrasting results as to the effects of therapy with several statins (atorvastatin, fluvastatin, simvastatin) at different doses on biochemical markers of bone remodelling. To date only one randomised trial has been published. This compares the effects of treatment with simvastatin and atorvastatin on the levels of biochemical markers of bone remodelling, but still with non-univocal results: only therapy with simvastatin (but not atorvastatin) reduced the levels of bone-specific alkaline phosphatase. To conclude, observational studies have shown a reduction in the risk of osteoporotic fractures with the use of statins, but it is not yet known whether using these drugs may have a beneficial effect on bone turnover. We must therefore await larger prospective randomised clinical trials before prescribing these drugs in osteoporotic patients.

Safe and successful endoarterial infusion of liposomal amphotericin B in treatment of mucormycosis.

Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We describe the case of a patient with septic fever and a necrotic lesion, with phlegmon of medial left thigh. Surgery was performed to drain the abscess content and to remove the necrotic tissue; mucormycosis was diagnosized by histological and culture tests and treated by intravenous amphotericin B. Since the lesion worsened, liposomal amphotericin B was directly infused into the left common iliac artery, with progressive improvement, and treatment was continued until complete recovery. Therefore, the endoarterial infusion of liposomal amphotericin B was a safe and successful treatment of advanced lesions of mucormycosis. In such lesions, intravenous general antibiotic administration probably is not sufficient to reach the whole infected area.

Results of double-blind placebo-controlled challenge with nickel salts in patients affected by recurrent aphthous stomatitis.

BACKGROUND: The aetiology of recurrent aphthous stomatitis (RAS) has so far not been completely clarified. Recently, several studies reported that patients affected by cutaneous diseases (i.e. dermatitis, eczema and urticaria) with positive patch test to nickel have a positive oral nickel challenge. OBJECTIVE: A retrospective data analysis of patch test and oral nickel challenge in 380 patients (204 women and 176 men) affected by RAS was performed. PATIENTS AND METHODS: We examined 380 consecutive patients affected by RAS during the period 1990-1999. In 28/380 patients the appearance of their oral symptoms coincided with the fitting of orthodontic appliance, while 352/380 reported that their oral symptoms worsened after the fitting of orthodontic appliance. All patients were studied with the series (European standard series and series for dental materials) for patch tests. RESULTS: Seventy out of 380 patients (18.4%) presented a contact sensitization to nickel sulphate (positive patch test). In all of these, the orthodontic appliance was replaced with one made of nickel-free materials. All patients were re-examined by the dentist 6 months after the removal of the orthodontic appliance. The symptoms had completely remitted in 28/70 patients, partially had improved in 31/70 patients and had remained unchanged in 11/70 patients. In all patients (n = 70) with a positive patch test to nickel we performed an oral double-blind placebo-controlled challenge (DBPC) test with nickel sulphate. The DBPC was positive in 32/70 patients, 21 of whom had partially improved and 11 had not, even after the replacement of the orthodontic appliance with material not containing nickel. None of the 28 patients in complete remission showed an adverse reaction to oral nickel challenge. CONCLUSION: The results of this study demonstrate that, in some patients with a positive patch test to nickel sulphate, the perpetuation of RAS can be related to a hypersensitivity to ingested nickel salts, independently of local contact to nickel.

Interleukin-12 in human boutonneuse fever caused by Rickettsia conorii.

Interleukin (IL)-12 contributes to the resistance against a number of intracellular pathogens. We examined the potential biological role of IL-12 by studying peripheral blood mononuclear cells (PBMC), its production and its effect on cytokine synthesis in 20 Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii. Data indicate that PBMC from acute BF patients were able to produce IL-12 in response to in vitro stimulation with rickettsial antigen (Ag): this production was higher than that detected in healed patients. Monocytes were the main source of IL-12 by PBMC from BF patients. IL-12 secretion by in vitro Ag-stimulated PBMC from BF patients was potentiated by recombinant interferon gamma (IFN-gamma) or anti-IL-10 monoclonal antibodies (MoAbs). Furthermore, the treatment with anti-IL-12 MoAbs reduced the IFN-gamma synthesis. These results indicate that treatment of PBMC from acute BF patients with IL-12 shifted the response toward a Th1-type cytokine response. Furthermore, IL-12 and IFN-gamma are interdependent and they may be associated with the immunity against rickettsias.