Severe anaphylaxis to sheep's milk cheese in a child desensitized to cow's milk through specific oral tolerance induction.

Specific oral tolerance induction to food (SOTI) is a new promising treatmentfor persistent IgE-mediatedfood allergy. Our paper reports a case of a 5-year-old girl with cow's milk allergy, who developed severe anaphylaxis after the ingestion of a croissant containing sheep's milk ricotta cheese, even though she had been previously desensitized to cow's milk through SOTI. The sheep's milk specific allergen causing the severe allergic reaction (a derivative of alpha-casein of 54,1kDa) was identified by SDS-PAGE and immunoblotting. We conclude that SOTI is a species-specific procedure and the induced tolerance to cow's milk doesn't necessarily provide protection against milk of other mammals. Therefore, children desensitized to cow's milk through SOTI should strictly avoid the intake of milk of other mammals, until tolerance to those kinds of milk is documented by an oral food challenge.

Rosaceae-associated exercise-induced anaphylaxis with positive SPT and negative IgE reactivity to Pru p 3.

BACKGROUND: Food-dependent-exercise-induced anaphylaxis (FDEIA) is characterized by anaphylactic symptoms after exercise following ingestion of food. We present a case of FDEIA induced by Rosacee fruits showing some diagnostic problems. MATERIAL AND METHODS: A 12 years-old boy with seasonal allergy to olive and cypressus pollens, experienced two distinct episodes of FDEIA, grade 4 and 3 of the Sampson Scale respectively, during intense exercise, about 30 minutes after eating a peach with peel or some cherries. SPT with commercial peach extract and fresh Rosacee fruits scored positive while SPT with a date palm profilin-enriched extract was negative. On in vitro tests total IgE were 44 kU/l and IgE for peach, cherry, Prup 3, Prup 1, Bet v 1, Bet v 2, Bet v 4 were negative. SPT with Prup 3 UniCAP device (cellulose polymer in a plastic reserve highly binding allergen protein) was negative. An oral food challenge, performed at rest using a commercial peach juice, scored negative. An immunoblot analysis performed with peach extract was negative. DISCUSSION: The main peculiarity of this case of FDEIA is the discrepancy between positive SPT and negative in-vitro findings. The positive SPT with the commercial peach extract suggested hypersensitivity to lipid transfer protein; however, no IgE reactivity to rPrup 3 was found in-vitro. The negative immunoblot analysis, possibly caused by the low levels of specific IgE, did not allow us to investigate the nature of the relevant allergen protein further. It is possible that this patient reacted to a different peach allergen or, alternatively, that he recognized an isoform of LTP that is different fr-om that in Uni-CAP. CONCLUSION: This case emphasizes once more the diagnostic relevance of SPT with extracts and fresh material to be performed before investigating IgE reactivity to single allergen components in-vitro.

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome.

BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. RESULTS: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. CONCLUSIONS: DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status.

Efficacy, safety and acceptability of the new pen needle 33G × 4 mm. AGO 01 study.

OBJECTIVES: Adherence to insulin therapy can be threatened by pain and needle fear. This cross-over randomized non-inferiority trial evaluated a new Pic Insupen 33G × 4 mm needle vs. a 32G × 4 mm needle in terms of metabolic control, safety and acceptability in patients with diabetes treated with insulin. RESEARCH DESIGN AND METHODS: We used a centralized, permuted block randomization, stratified by center and maximum insulin dose per single injection. Subjects used the two needles in two 3 week treatment periods. The primary endpoint was the absolute percentage variation of the blood fructosamine between the two treatments (% |ΔFru|). Additional endpoints were: glycemic variability, total insulin doses, body weight, severe hypoglycemic episodes, leakage at injection sites and pain measured by visual analogue scale. Equivalent glycemic control was defined a priori as % |ΔFru| (including 95% CI) within 20%. RESULTS: Of 87 subjects randomized, 77 completed the study (median age 53.1 [IR 42.3-61.2], median BMI 24.3 Kg/m(2) [IR 21.3-28.5], median duration of insulin therapy [in months] 141.4 (IR 56.3-256.9), median baseline HbA1c 7.9% [IR 7.2-8.8]). The % |ΔFru| was 7.93% (95% CI 6.23-9.63), meeting the non-inferiority criterion. The fasting blood glucose standard deviation was 46.2 (mean 154.6) with the 33G needle and 42.8 (mean 157.3) with the 32G needle (p=0.42). Insulin daily dose and patients' weight did not show any statistically significant variation. We observed 95 episodes of symptomatic hypoglycemia with the 33G needle and 96 with the 32G needle. One episode of severe hypoglycemia was documented in the latter group. As for insulin leakage we observed 37.55 episodes per 100 patient-days with the 33G needle and 32.21 episodes per 100 patient-days with the 32G needle (p=0.31). Patients reported less pain with the 33G × 4 mm needle (p=0.05). STUDY LIMITATIONS: Study sample was mainly composed of adults with type 1 diabetes and study was not blinded. CONCLUSIONS: The 33G needle is not inferior to the 32G needle in terms of efficacy and safety, with reduced pain and no difference in insulin leakage. CLINICAL TRIAL REGISTRATION: NCT01745549.

Plasma levels of coenzyme Q(10), vitamin E and lipids in uremic patients on conservative therapy and hemodialysis treatment: some possible biochemical and clinical implications.

Coenzyme Q(10) (CoQ(10)), vitamin E, total cholesterol, HDL-cholesterol (HDLC) and triglycerides were measured in the plasma of 62 patients with kidney failure, 46 under hemodialysis treatment and 16 under conservative therapy, and 95 controls. The sum of LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C) was also calculated for each patient. The ratio CoQ(10)/LDL-C+VLDL-C in both conservative therapy and hemodialysis populations was significantly lower (P<0.001) compared with normal controls and remained unchanged after the dialysis treatment. On the contrary the ratio vitamin E/LDL-C+VLDL-C was normal but decreased significantly (P<0.02) after each dialysis. Since coenzyme Q is the main inhibitor of the prooxidant action of vitamin E, it was hypothesized that its decrease in both the populations examined could make the lipoproteins of these patients more vulnerable to a peroxidative attack.

Sestamibi imaging and echocardiography: a combined approach to myocardial infarction.

The resting relationship of MIBI segmental uptake to regional wall motion has been studied in 30 patients with postinfarction wall motion abnormalities. The purpose of this study was to verify whether an integrated approach using Sestamibi (MIBI) imaging (perfusion analysis) combined with echocardiography (ECHO) (wall motion analysis) could present an additive value to differentiate infarcted from viable myocardial areas with respect to MIBI imaging alone. The same 11 segments model for left ventricle was used to compare segmental wall motion scores versus segmental uptake scores using a chi 2 analysis. The global score frequency rates for MIBI and ECHO were examined and a subsequent comparative analysis score versus score on each segment was performed. Our data, based on a chi 2 analysis, indicated that MIBI imaging overestimates the effective area of necrosis, underestimating, furthermore, hypoperfused but non-necrotic myocardium. We can conclude that an integrated approach based on both segmental perfusion and wall motion analysis, seems to be clinically suitable for a correct evaluation of infarcted patients, especially in view of revascularization procedures, providing an additive value in discriminative capacity, with respect to MIBI scintigraphic analysis alone.

[Clinical use of echo-dipyridamole test in hypertensive subjects with suspected ischemic heart disease]. / Impiego clinico del test eco-dipiridamolo in soggetti ipertesi con sospetta cardiopatia ischemica.

The aim of this study was to assess the diagnostic capacity of the dipyridamole-echocardiography test (DET) and dipyridamole myocardial scintigraphy (DMS) for coronary artery disease in mild to moderate hypertensive subjects with chest pain. A comparison was performed with exercise stress test (EST) and stress myocardial scintigraphy (SMS) in 20 subjects. Seven patients also underwent coronary angiography. To compare test results, Mc Nemar test was employed. Our results showed a statistically significant difference between DET and EST and a good agreement, in terms of dichotomy response, between DET and SMS. Any difference was further found between SMS and DMS. In conclusion, in hypertensive subjects, DET appears to provide a useful clinical noninvasive tool for coronary artery disease diagnosis and evaluation.

Clinical features of subjects with mitral valve prolapse: a study with 24-hour ambulatory blood pressure monitoring.

The present case-control study provides evidence that the correlation between mitral valve prolapse and the clinical observation of low blood pressure persists throughout a 24-hour period as documented by ambulatory blood pressure monitoring. Moreover, the blood pressure circadian rhythm, even though preserved, seems to follow a different course over the 24-hour period in subjects with mitral valve prolapse.

Blood pressure circadian rhythm and variability in subjects with severe heart failure.

To explore whether a condition of severe heart failure results in alteration of the 24-h-blood pressure (BP) profile and BP circadian rhythm, 19 patients with severe heart failure (NYHA class III-IV, 17M, 2F, mean age 57+/-8 years) were considered and compared to a control group of age- and sex-matched normal subjects. All subjects were submitted to non-invasive 24-h ambulatory blood pressure monitoring using a SpaceLabs 90207 unit (recording interval 15 min). Both systolic and diastolic BP profiles were evaluated using the two-step method of analysis reported by Staessen: the existence of a BP circadian rhythm was first tested using Siegel's runs test, then a Fourier multiple harmonic analysis allowed us to obtain the BP profile parameters Acrophases (Acro, hh:mm) and Amplitudes (Ampl, mm Hg). The same methods were used for pulse rate. Our results showed the presence of a BP circadian rhythm in severe heart failure subjects, as well as in control subjects. Furthermore, no significant difference was found between the two groups when considering the BP profile parameters Acro and Ampl. In conclusion, in contrast with previous reports, our results show that both BP circadian rhythm and BP profile parameters are preserved in patients with severe heart failure.

Prevalence of hypertension in acromegalic patients: clinical measurement versus 24-hour ambulatory blood pressure monitoring.

OBJECTIVE: Hypertension is thought to play an important role in the pathogenesis of acromegalic cardiomyopathy. So far, hypertension has been defined by clinical measurement, with considerable variations reported concerning its prevalence in acromegalics. DESIGN: To determine the mean blood pressure (BP) values and the prevalence of hypertension in patients with active acromegaly according to non-invasive 24-hour ambulatory BP monitoring (ABPM) and to compare the data obtained with those provided by clinical measurement. PATIENTS: Forty patients with active acromegaly (22 women, 18 men, mean age 48.6 +/- 12.5 years) were included. Patients were in wash-out for antihypertensive treatment and none had been using any medical treatment for acromegaly for at least 3 months before the study. All were studied as outpatients. MEASUREMENTS: Clinical BP values were calculated as the mean of BP values obtained by standard sphygmomanometric measurement in three separate occasions. Mean 24-hour, daytime and night-time BP values were obtained by ABPM. RESULTS: The mean 24-hour BP values were lower than clinical BP values, the difference being significant for both systolic BP (SBP: 131.1 +/- 21.5 versus 136.1 +/- 16.3 mmHg, P < 0.02) and for diastolic BP (DBP: 74.6 +/- 10.6 versus 88.8 +/- 9.1 mmHg, P < 0.0001). ABPM values recorded during the daytime were 137.8 +/- 20.9 mmHg for SBP and 78.6 +/- 11.5 mmHg for DBP, the latter being significantly lower than the corresponding clinical BP values (P < 0.0001). About 60% of the patients considered hypertensive by clinical measurement were found to be normotensive by ABPM, thereby decreasing the prevalence of hypertension in this series from 42.5% to 17.5% according to ABPM (P < 0.02). In contrast, all patients defined as normotensive by clinical measurement were also normotensive by ABPM. CONCLUSIONS: Ambulatory blood-pressure monitoring indicated a lower prevalence of hypertension in acromegalic patients then usually reported, suggesting that the role of hypertension in the pathogenesis of acromegalic cardiomyopathy is commonly overestimated. We propose that ambulatory blood-pressure monitoring should be routinely proposed in acromegalics with high or borderline clinical blood pressure values although it is not useful in patients defined normotensive according to repeated clinical measurement.