G. Di Fede

Thromboxane B2 formation and platelet sensitivity to prostacyclin in insulin-dependent and insulin-independent diabetics.

TxB2 formation in PRP after thrombin stimulus, serum TxB2 and platelet sensitivity to prostacyclin and the correlation with ambient fasting plasma glucose and lipoproteins were determined in 20 insulin-independent diabetics (IID) with macroangiopathy, 10 insulin-dependent diabetics (IDD) with microangiopathy and 30 matched controls. Platelets obtained from insulin-independent diabetics synthetize significantly higher amounts of TxB2 than those of insulin-dependent diabetics and matched controls. IDD and IID patients required significantly higher concentrations of prostacyclin (p less than 0.001) for a similar degree of platelet aggregation inhibition. The amount of prostacyclin required for 50% platelet aggregation inhibition was correlated with fasting plasma glucose (r = 0.64, p less than 0.001) and HbA1% (r = 0.48, p less than 0.01) in all diabetic subjects. We conclude that: 1) only PRP, obtained from some insulin-independent diabetics with a concomitant macroangiopathy, shows an increased synthesis of TxB2; 2) platelet sensitivity to prostacyclin is highly dependent on the fasting ambient plasma glucose.

Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome

Objective:  Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined.

Hypogonadism and Hormone Replacement Therapy on Bone Mass of Adult Women with Thalassemia Major

We studied bone mass and metabolism in 30 adult women (age 28.5 ± 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine −1.29 ± 0.31; femoral neck −0.60±0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine −2.35 ± 0.2, femoral neck −1.83 ± 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 ± 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

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.

Haematological deficiencies in patients with recurrent aphthosis

Background  Recurrent aphthosis is a common oral ulcerative condition consisting also of a subset of similar ulcers, properly named ‘aphthous‐like’ ulcers (ALU), linked to systemic diseases and among these, to iron, folic acid and vitamin B12 deficiencies.

The use of zoledronic acid in patients with bone metastases from prostate carcinoma: effect on analgesic response and bone metabolism biomarkers

Abstract Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers. Eligibility for this study required prostate cancer patients with metastatic bone disease and pain not controlled by analgesics. Patients were excluded from the study if they were receiving cytotoxic chemotherapy or radiation therapy within three months. Eighteen patients (75%) were considered responder to acid zoledronic, only 6 patients did not respond. Before starting treatment (T0) mean Visual Analogue Scale was 7.8 (SE +/− 0.29), after 1 month therapy (T1) was 3.6 (SE +/− 0.3) and after three months (T2) was 3.1 (SE +/− 0.4) with a significant difference between T0 and T1 (p<0.0005) and between T0 and T2 (p<0.0005). Visual Analogue Scale improvement was positively correlated with decrease of C-telopeptide and bone phosphatase alkaline (p<0.05) serum levels.

FokI Polymorphism of the Vitamin D Receptor Gene Correlates with Parameters of Bone Mass and Turnover in a Female Population of the Italian Island of Lampedusa

One of the most promising genetic approaches to dissecting a multifactorial disease is represented by genetically isolated population studies. We studied a genetic marker in a cohort of women living on the Mediterranean island of Lampedusa, a geographically isolated population. Lampedusa, located between the African coast and Sicily, consists of a young genetic isolate (<20 generations) with an exponential growth in the last generations. We analyzed the association between the FokI vitamin D receptor (VDR) gene polymorphism, previously proposed as a predictor of bone mass, with parameters of bone mass and turnover in a cohort of pre- and postmenopausal women living on Lampedusa. In 424 women (277 postmenopausal and 147 premenopausal), allelic frequencies were 49% for the F allele and 51% for the f allele. Using analysis of covariance, we found that subjects with ff genotype exhibited a significantly (P < 0.001) lower lumbar spine bone mass, by dual-energy X-ray absorptiometry, and lower values of bone ultrasonographic parameters (speed of sound and broadband ultrasound attenuation) relative to those with Ff and FF genotypes. Conversely, osteocalcin and serum cross-laps were significantly higher in ff and Ff compared to FF genotype. Our data suggest that FokI VDR polymorphism may contribute to the determination of bone mass and turnover in both pre- and postmenopausal women in this geographically isolated population.

In Vitro Effects of Aminobisphosphonates on Vγ9Vδ2 T Cell Activation and Differentiation

In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vγ9Vδ2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vγ9Vδ2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vγ9Vδ2 T cell subsets, with decrease of Tnaive and TCM cells and increase of TEM and TEMRA Vγ9Vδ2 cells, indicating that in vitro treatment with aminobisphosphonates induces Vγ9Vδ2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vγ9Vδ2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-γ and acquired the ability to kill tumor target cells.

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 ECNFs 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. ECNFs median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNFs 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. ECNFs 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. ECNFs median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was ≤ 5.0, AUC = 0.94. ECNFs 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 ≤ 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 ECNFs performance was moderately accurate in distinguish patients with AR and NAR.

A key role for abdominal ultrasound examination in "difficult" diagnoses of celiac disease.

PURPOSE To evaluate the usefulness of abdominal ultrasound examination (US) for the diagnostic workup of cases of suspected CD involving negative serum antibodies and difficult diagnosis. MATERIALS AND METHODS 524 consecutive patients with symptoms of suspected CD underwent an extensive diagnostic workup. 76 (14 %) were excluded since they were positive for serum anti-tTG and/or EmA antibodies. 377 were excluded since they were diagnosed with something other than CD or did not have the alleles encoding for HLA DQ 2 or DQ 8. A diagnosis of CD with negative serum antibodies was probable in 71 patients who underwent abdominal US and duodenal biopsy for histology evaluation. RESULTS Intestinal histology and subsequent clinical and histological follow-up confirmed the CD diagnosis in 12 patients (GROUP 1) and excluded it in 59 subjects (GROUP 2). Abdominal US showed that the presence of dilated bowel loops and a thickened small bowel wall had a sensitivity of 83 % and a negative predictive value (NPV) of 95 % in CD diagnosis. Furthermore, in 11 of the 12 CD seronegative patients there was at least one of these two abdominal US signs. Therefore, considering the presence of one of these two signs, abdominal US sensitivity increased to 92 % and NPV to 98 %. CONCLUSION Abdominal US is useful in the diagnostic workup of patients with a high clinical suspicion of CD but with negative serology.