Heterozygous nonsense SCN5A mutation W822X explains a simultaneous sudden infant death syndrome

The sudden, unexpected, and unexplained death of both members of a set of healthy twins (simultaneous sudden infant death syndrome (SSIDS)) is defined as a case in which both infants meet the definition of sudden infant death syndrome individually. A search of the world medical literature resulted in only 42 reported cases of SSIDS. We report the case of a pair of identical, male, monozygotic twins, 138 days old, who suddenly died, meeting the full criteria of SSIDS and where a genetic screen was performed, resulting in a heterozygous nonsense SCN5A mutation (W822X) in both twins. Immunohistochemistry was performed on cardiac tissue samples utilizing polyclonal antibodies anti-Na(+) CP type Valpha (C-20) and a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. The cellular localization of the Na(+) CP type Valpha (C-20) demonstrated by confocal microscopy on staining pattern of myocytes was concentrated in the intercalated disks of ventricular myocytes. These findings suggest that defective ion channels represent viable candidates for the pathogenesis of SIDS and, obviously, of SSIDS, supporting a link between sudden infant death syndrome and cardiac channelopathies.     

Does gabexate mesilate affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination?

BACKGROUND/AIMS: To explore the possibility that the preventive effect of gabexate mesilate on endoscopic retrograde cholangiopancreatography-related acute pancreatitis may be mediated by its modulation of acute phase proteins. METHODOLOGY: Thirty consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomly assigned to receive 1g of gabexate mesilate (13 patients) or a placebo (17 patients) by continuous i.v. infusion starting 30 minutes before the endoscopy session and continuing for 12 hours afterward. In all patients, C-reactive protein, serum amyloid A and interleukin 6 serum concentrations were determined before endoscopy and 4, 8, 12 and 24 hours afterward. RESULTS: Interleukin 6 basal serum concentrations were not statistically different between patients who had been treated with gabexate mesilate and those who had received the placebo (P = 0.279), whereas C-reactive protein (P = 0.033) and serum amyloid A (P = 0.022) basal values were significantly lower in the gabexate mesilate group than in the placebo group. Compared to basal values, serum interleukin 6 concentrations significantly increased at 4 (P = 0.048) and at 8 (P = 0.025) hours; the increase of serum interleukin 6 concentrations was not significant at 12 (P = 0.092), but became significant at 24 (P = 0.025) hours. C-reactive protein and serum amyloid A serum concentrations increased significantly only at 12 (P = 0.001, P = 0.012, respectively) and 24 (P < 0.001, P = 0.013, respectively) hours. The modifications of serum concentrations of interleukin 6, C-reactive protein and serum amyloid A were not significantly different between the gabexate mesilate and the placebo groups. CONCLUSIONS: Gabexate mesilate does not affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination and it is able to prevent acute pancreatitis related to endoscopic retrograde cholangiopancreatography via a different mechanism than that explored in this study.     

Impact of in-hospital intravenous iron supplementation on red blood cell transfusions: experience from an Internal Medicine Unit

BackgroundPharmacological treatment of iron deficiency anaemia can reduce red blood cell (RBC) transfusions. Intravenous iron provides a more effective and quicker correction of iron deficiency anaemia than oral iron, and third-generation high-dose intravenous iron formulations allow the complete correction of iron deficiency with just one or two drug infusions, thus facilitating iron supplementation therapy and reducing transfusion requirement.Material and methodsIn an observational, retrospective study we compared RBC transfusion requirement during hospitalisation and within 3 months of hospital discharge in 88 patients with iron deficiency anaemia treated with high-dose ferric carboxymaltose and in 85 patients treated with ferric gluconate while hospitalised in the Internal Medicine unit of our Institution.ResultsFerric carboxymaltose reduced the number of RBC units given to each transfused patient during hospitalisation (1.81±0.84 vs 2.39±1.49, p=0.011). At hospital discharge, fewer ferric carboxymaltose patients were prescribed home therapy with iron. No differences between treatment groups were observed in the proportion of patients or the number of RBC units transfused within 3 months of discharge. At one month from discharge, however, only 2 ferric carboxymaltose patients had been transfused compared with 7 ferric gluconate patients (p=0.078). Patients transfused post-discharge were more likely to have an underlying malignancy and/or higher serum creatinine concentrations.DiscussionTreatment with ferric carboxymaltose reduced the number of RBC units per transfused patient. Larger studies are required to define risk factors associated with post-discharge transfusion requirement and to establish if home therapy with iron will reduce subsequent transfusions in patients treated with ferric carboxymaltose.     

Long-standing type 1 diabetes: patients with adult-onset develop celiac-specific immunoreactivity more frequently than patients with childhood-onset diabetes,in a disease duration-dependent manner

To assess the frequency of celiac-associated humoral autoimmunity in patients with long-standing childhood- and adult-onset type 1 diabetes (LDM1) and whether it occurs more frequently as the disease progresses. IgA-/IgG-anti-tissue transglutaminase (IgA-tTG and IgG-tTG) and IgA-/IgG-deamidated gliadin (DGP) antibodies were analyzed in 277 LDM1 sera (120 females; disease duration 19.3 ± 12.3 years, range 5.0–54.0 years). Of the 277 patients, 147 were childhood-onset LDM1 (^CHLDM1) and 130 adult-onset LDM1 (^ADLDM1); 6.1 % LDM1 sera were tTG- and/or DGP-antibody-positive, with a lower frequency among ^CHLDM1 as compared with ^ADLDM1 patients (3.4 vs 9.2 %, p = 0.048). Celiac-associated immunoreactivity was significantly more frequent in LDM1 with >15 years of disease duration (9.4 vs 2.9 % in those with ≤15 years, p = 0.042) and among them in ^ADLDM1 (14.7 vs 4.2 % ^CHLDM1, p = 0.043). Celiac disease humoral immunoreactivity should be screened not only at diabetes onset, but also in long-standing patients, especially adults with disease duration >15 years.     

Serum level of KL-6 as a marker of interstitial lung disease in patients with juvenile systemic sclerosis

OBJECTIVE: Serum KL-6 has been found to be elevated in diseases characterized by diffuse interstitial lung involvement. The purpose of this study was to evaluate serum KL-6 as a marker of interstitial lung disease (ILD) in patients with juvenile systemic sclerosis (JSS). METHODS: Serum concentrations of KL-6 were measured with an immunoassay in 39 serum samples from 12 children with diffuse cutaneous form of JSS (6 patients with and 6 patients without ILD) and from 20 healthy controls comparable for age. In patients sampled serially, the relationship of KL-6 concentrations with the severity of ILD and its response to treatment were evaluated. RESULTS: Serum concentrations of KL-6 were significantly higher in patients with ILD (1687 +/- 979 IU/ml) than in patients without (345 +/- 95 IU/ml, p < 0.01) and healthy controls (311 +/- 114 IU/ml, p < 0.001). Serum KL-6 concentrations of patients without ILD were not statistically different from those of healthy controls. We found a significant correlation of serum KL-6 concentrations with vital capacity and with diffusing capacity for carbon monoxide (DLCO). Analysis of individual patients showed that serum concentrations of KL-6 were correlated with ILD severity and its response to treatment. CONCLUSION: Measurement of serum KL-6 concentration is a useful noninvasive marker of pulmonary fibrosis in children with JSS. Its advantages over conventional methods of ILD assessment, such as pulmonary function test and high-resolution computerized tomography, are that it is easy to quantify and to measure repeatedly and it does not need children's cooperation.     

Early haemoglobin-independent increase of plasma erythropoietin levels in patients with acute myocardial infarction.

AIMS: We studied plasma erythropoietin (EPO) levels and their relation with CD34(+)VEGFR-2(+) (mature and progenitor endothelial cells) and CD34(+) CD133(+)VEGFR-2(+), or CD34(+) CD117(+)VEGFR-2(+) (early/immature endothelial progenitors) cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Fifty AMI patients undergoing percutaneous coronary intervention (PCI) within 6 h of symptom onset were enrolled. EPO, measured by ELISA, and cell subsets, by cytofluorimetric analysis, were evaluated before PCI, 24 h and 7 days afterwards. Forty-five healthy subjects (CTRLs) were studied. Plasma EPO levels were higher in AMI patients at admission, 24 h, and 7 days (P = 0.04, P = 0.0001, P = 0.001, respectively) than in CTRLs. No correlation was evidenced between EPO and haemoglobin (Hb) or haematocrit at admission or 24 h after AMI. Differently, both Hb and haematocrit inversely correlated with EPO at day 7 (P = 0.0016, P = 0.029, respectively). Plasma EPO levels correlated with CD34(+)CD133(+)VEGFR-2(+) cells at day 7 (P = 0.03). CONCLUSION: AMI patients have increased plasma EPO levels until day 7. In the early phase, plasma EPO levels are Hb-independent; at day 7, an Hb-modulated increase of EPO correlates with the percentage of CD34(+)CD133(+)VEGFR-2(+) cells.     

Off-pump myocardial revascularization in patients with multivessel coronary disease]

BACKGROUND: Some criticisms have been addressed to off-pump coronary surgery technique concerning the possibility of its systematic use with the respect of the completeness of revascularization. We report our experience with off-pump revascularization in patients with multivessel coronary disease. METHODS: Between September 1997 and April 2003, 868 patients with multivessel coronary disease were scheduled for off-pump surgical revascularization. From September 2000, the percentage of patients operated on without cardiopulmonary bypass has been stably > 90%. Fifteen patients (1.7%) had a conversion to cardiopulmonary bypass for anatomical reasons (n = 6) or clinical instability (n = 9). RESULTS: An average of 2.5 +/- 0.8 (range 1-5) anastomoses per patient were completed. Bilateral mammary artery was used in 573 patients (66%); totally arterial revascularization was accomplished in 479 patients (55.2%). In-hospital mortality rate was 0.6% (5 patients). Total incidence of non-fatal postoperative complications (bleeding requiring re-exploration, perioperative myocardial infarction, stroke, new onset of acute renal failure) was 3.5%. Mean postoperative hospital stay was 4.8 +/- 3.8 days. At a mean follow-up of 21.6 +/- 15.6 months (range 1-65 months), the postoperative actuarial survival rates were 97.3, 93.7 and 86.7% at 1, 3 and 5 years postoperatively. Actuarial freedom rates from new revascularization were 98.7, 96.6 and 96.6% at 1, 3 and 5 years postoperatively. CONCLUSIONS: Early- and intermediate-term results of this study demonstrate the feasibility of off-pump revascularization in all patients with multivessel coronary disease, respecting the criterion of complete myocardial revascularization.