A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome

We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype–phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy‐six non‐related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation‐dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild‐type probands. There were non‐significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.     

Precise intraoperative location of gastrointestinal bleeding with a hand-held counter. Work in progress

The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding.     

Stem Cell Migration and Proliferation During Severe Anemia

The pluripotential stem cell (CFU) compartment of marrow and spleen wasevaluated in mice subjected to an intense erythroid stimulus associated withphenylhydrazine-induced anemia. Erythroid hyperplasia occurred in both marrow and spleen. CFU in the marrowgradually declined to approximately 50per cent of control levels (day 5) whiletheir numbers in the spleen increased(fourfold) by day 3 and were maintainedat this level for several days. Thesechanges in numbers of marrow andsplenic CFU were not associated withCFU proliferation. Thereafter, CFU inthe marrow, but not in the spleen, entered active cell cycle. The data suggestthat CFU migrate from marrow to spleenduring the demands of severe anemia.The induction of marrow CFU into cyclefurther suggests a negative feedback,which, perhaps through cell-cell interaction, maintains stem cells at a criticalcompartment size. The failure of splenicCFU to cycle may reflect the converseeffect, i.e. an inhibition on stem cell proliferation in the wake of an expandedstem cell pool.

Submitted on March 17, 1970 Revised on May 14, 1970 Accepted on June 9, 1970     

Catheter Ablation in the Canine Coronary Sinus Using Radiofrequency Energy

This study was performed to evaluate the effects of radiofrequency catheter ablation in the coronary sinus as a potential means of eliminating conduction over left-sided accessory pathways in humans. Radiofrequency current at a frequency of 500 kHz was delivered by electrode catheter to two sites in the coronary sinus of each often dogs. Left coronary arteriography with venous phase visualization of the coronary sinus was performed before, immediately after, and 2 weeks following ablation. Unipolar electrograms from the ablating electrode were recorded before and immediately after ablation. Coronary arteriography revealed no evidence of damage to the adjacent left circumflex coronary artery or its branches as a result of ablation. Contrast visualization of the coronary sinus showed persistent contrast staining following ablation at two of the ablated sites. Angiographically apparent stenosis of the coronary sinus was seen both acutely and chronically in two cases. Unipolar electrogram recordings from the ablating electrode showed an increase in atrial repolarization voltage (atrial current of injury) of 1.53 ± 1.03 mV (P = 0.00004), and an increase in ventricular repolarization voltage of 0.73 ± 0.84 mV (P = 0.005). There was a 23% decrease in amplitude of atrial electrograms (P = 0.006) and a 7% decrease in amplitude of ventricular electrograms (P = 0.02) recorded from the ablating electrode following ablation. Lesions could be identified grossly and microscopically at 16 of the 20 ablated sites. Perforation of the coronary sinus did not occur. Microscopical observation showed normal healing with granulation tissue and fat necrosis extending outward from the coronary sinus involving the atrial epicardium in 13 lesions, the ventricular epicardium in 5 lesions, and the adventitia of the left circumflex coronary artery in 5 lesions. No medial or intimal involvement of the coronary artery was seen. The coronary sinus itself showed luminal organized thrombus in 4 lesions, with near occlusion of the lumen in 1 case. Radiofrequency ablation in the coronary sinus thus results in lesions of a size and extent that would be expected to successfully ablate some left-sided accessory pathways if delivered in humans. Monitoring of the unipolar electrogram provides insight into the extent of injury during ablation. In some cases, thrombosis of the coronary sinus occurs, the long-term effects of which are not known.     

Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1

We determined the prevalence of antibody to cytomegalovirus (CMV) in the sera of non-homosexual hemophilia patients and homosexual men infected with the human immunodeficiency virus type 1 (HIV-1). CMV antibody testing by latex agglutination revealed 33 of 58 HIV-1 infected hemophiliacs (57%) were antibody-positive compared with 54 of 54 HIV-1 infected asymptomatic non-hemophiliac homosexuals (100%) (p less than .001). Nine of 15 hemophiliacs (60%) with symptomatic HIV-1 infection were CMV antibody-positive. We also tested 22 HIV-1 antibody-negative hemophiliacs who had received non-heat treated factor concentrates. 14 of these 22 (64%) were CMV antibody-positive compared with 57% of HIV-1 antibody-positive hemophiliacs. We conclude 1) there is little correlation between transmission of HIV-1 and CMV by factor concentrates, 2) the presence of CMV antibody does not appear to be associated with clinical stage of HIV-1 infection in hemophiliacs, and 3) there may be a significant number of CMV antibody-negative hemophiliacs with HIV-1 infection at risk for primary infection and subsequent disease if CMV seronegative blood products are not provided for future transfusions.     

Dietary oleic acid is inversely associated with pancreatic cancer – Data from food diaries in a cohort study

Background

Dietary oleic acid may prevent pancreatic ductal adenocarcinoma (PDA) by reducing hyperinsulinaemia which can otherwise promote DNA damage and tumour growth. Results from previous epidemiological studies investigating oleic acid are inconsistent. This study aims to clarify the relationship between dietary oleic acid intake and the risk of developing PDA using nutritional information from food diaries plus published serum biomarker data from HbA1c.