Enzo Ballone

Prognostic Value of Different Indices of Blood Pressure Variability in Hypertensive Patients

BACKGROUND The independent prognostic significance of different indices of blood pressure (BP) variability is not clear. We investigated the prognostic value of BP variability estimated as s.d. or average real variability (ARV) of daytime and night time BP, in hypertensive patients. METHODS The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1,280 sequential hypertensive patients (550 initially untreated and 730 initially treated) aged > or =40 years. Subjects with s.d. or ARV of daytime or night time systolic or diastolic BP below or above the median were classified as having low or high BP variability. RESULTS During the follow-up (4.75 +/- 1.8 years), 104 cardiovascular events occurred. The event rate per 100 patient-years was 1.71 in the global population. After adjustment for other covariates, Cox regression analysis showed that cardiovascular risk was higher in subjects with high ARV of daytime systolic BP in initially untreated, initially treated, and all the subjects (high vs. low ARV, hazard ratio (HR) 2.29 (1.06-4.94), HR 1.90 (1.06-3.39), and HR 2.07 (1.31-3.28), respectively). ARV of daytime diastolic BP and night time BP, and s.d. of daytime and night time BP were not significantly associated with risk or were not independent predictors of outcome. CONCLUSIONS In this study, high ARV of daytime systolic BP resulted in an independent predictor of cardiovascular risk in hypertensive patients, while high s.d. did not. Our data suggest that, in comparison to s.d., ARV could be a more appropriate index of BP variability and a more useful predictor of outcomes.

Nickel oral hyposensitization in patients with systemic nickel allergy syndrome

Abstract Background: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with “systemic nickel allergy syndrome” (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Methods: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5th month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. Results: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. Conclusions: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.

Symptoms discriminate irritable bowel syndrome from organic gastrointestinal diseases and food allergy.

Background The value of specific gastrointestinal symptoms in discriminating irritable bowel syndrome (IBS) from organic disease has been documented. In contrast, there have been few attempts to identify symptoms that discriminate irritable bowel syndrome from food allergy, despite similarities in their respective symptom complexes. We aimed to investigate the value of symptoms in discriminating irritable bowel syndrome from organic disease and food allergy. Methods Subjects (n = 288) were recruited from consecutive patients presenting to the Internal Medicine, Gastroenterology and Allergy Units in Chieti. Patients completed the validated Bowel Disease Questionnaire (BDQ) prior to an independent diagnostic evaluation, which included endoscopy when appropriate. Food allergy was diagnosed using a 2‐week elimination diet, followed by a placebo‐controlled food challenge test, a skin prick test and serum RAST for specific IgE for suspected foods or additives. The results of the BDQ were not considered in formulating a diagnosis. In total, 99 patients were diagnosed with the IBS, 79 patients were diagnosed with organic disease and 22 patients were diagnosed with food allergy. A further 88 patients with extraintestinal allergies were included as a control group. Results Based on logistic regression analysis, six symptom items discriminated IBS from organic disease, while five symptoms discriminated patients with IBS from control subjects. A diagnosis of IBS compared to organic disease was positively associated with straining on defaecation (P = 0.0001), diarrhoea (P = 0.001) and abdominal bloating (P = 0.01), but was negatively associated with pain in the upper abdomen (P = 0.0004), reflux (P = 0.0001) and appetite loss (P = 0.004). A diagnosis of IBS compared to extraintestinal allergy was positively associated with pain relieved by bowel movement (P = 0.0001), pain in the lower abdomen (P = 0.0006), pain in both the upper and lower abdomen (P = 0.003), frequent pain (P = 0.001) and abdominal bloating (P = 0.0009). In comparison between IBS and food allergy patients, a diagnosis of IBS was positively associated with pain in the lower abdomen (P = 0.001), pain relieved by bowel movements (P = 0.001), frequent pain (P = 0.02) and abdominal bloating (P = 0.03). Conclusion Symptoms appear to be useful for discriminating IBS from organic gastrointestinal disease and food allergy. Eur J Gastroenterol Hepatol 12:981‐988

The Effect of Delaying Adjuvant Radiation Treatment after Conservative Surgery for Early Breast Cancer

Abstract:  We examined the effect of delaying radiation treatment after conservative surgery on the risk of breast cancer local recurrence (LR). From January 1997 to December 2001, 969 women with early‐stage breast cancer were treated at the Radiation Oncology Department in Chieti. We analyzed 802 of them who underwent conservative surgery followed by whole‐breast radiotherapy. The patients were divided into two groups: women who did not receive chemotherapy and women who received chemotherapy. The time intervals from surgery to breast irradiation used for the analysis were <16 or more weeks for no‐chemotherapy‐treated women, and <25 and 25 or more weeks for chemotherapy‐treated women. The relationship between LR and factors such as age, tumor size, margin status, and surgery‐radiotherapy time interval was evaluated. The 8‐year LR risk was estimated using the Kaplan–Meier method. LR was observed in 33 (4.1%) of the 802 patients. The overall 8‐year LR risk was 6.5% (±1.51). In the no‐chemotherapy group, the risk of LR was associated with a younger age and a positive margin status. In the chemotherapy group LR was associated with a younger age and a tumor size >3 cm. Surgery‐radiotherapy interval was not associated with LR in both groups of patients. Delay in the start of radiotherapy does not increase the risk of LR in patients with early breast cancer treated or not treated with chemotherapy.

Dose-dependent clinical and immunological efficacy of sublingual immunotherapy with mite monomeric allergoid.

Sublingual immunotherapy with monomelic carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergen-driven Th1, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time of the inclusion and after 6 and 12 months of treatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After 1-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-γ secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.

The Immunological Effects of Dust Containing Metals and Compounds in Workers of a Plant Producing Plastic Materials. Preliminary Study

Lymphocyte subpopulations were studied in 14 men working in a plant producing plastic materials in comparison with a control group of similar age and smoking habit. The workers were exposed to dust containing particles of calcium carbonate, polyvinylchloride, phtalates, unsaturated oils, paraffin wax, iron oxides, titanium bioxides, barium, zinc, lead and lead chromate. In the exposed workers, T helper/ inducer lymphocytes (mainly CD4+-CD45RO- “virgin” lymphocytes) and CD19+ B lymphocytes were significantly reduced without changes of serum IgM, IgG and IgA. A highly significant correlation was found between B lymphocytes (reduced in the workers about 40 %) and CD4+-CD45R0+ “memory” lymphocytes (reduced about 20 %). Moreover, blood lead (correlated with urinary chromium) demonstrated a highly significant negative correlation with B lymphocytes. This study demonstrates that combined exposure to toxic agents produces specific modifications in the lymphocyte subsets without changes in immunoglobulins and confirms the results of previous studies showing that the exposure to lead or chromate induces reduction of lymphocytes in the peripheral blood.