Familial atrial fibrillation mutation M1875T-SCN5A increases early sodium current and dampens the effect of flecainide.

AIMS: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Pathogenic variants in genes encoding ion channels are associated with familial AF. The point mutation M1875T in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Nav1.5, has been associated with increased atrial excitability and familial AF in patients. METHODS AND RESULTS: We designed a new murine model carrying the Scn5a-M1875T mutation enabling us to study the effects of the Nav1.5 mutation in detail in vivo and in vitro using patch clamp and microelectrode recording of atrial cardiomyocytes, optical mapping, electrocardiogram, echocardiography, gravimetry, histology, and biochemistry. Atrial cardiomyocytes from newly generated adult Scn5a-M1875T+/- mice showed a selective increase in the early (peak) cardiac sodium current, larger action potential amplitude, and a faster peak upstroke velocity. Conduction slowing caused by the sodium channel blocker flecainide was less pronounced in Scn5a-M1875T+/- compared to wildtype atria. Overt hypertrophy or heart failure in Scn5a-M1875T+/- mice could be excluded. CONCLUSION: The Scn5a-M1875T point mutation causes gain-of-function of the cardiac sodium channel. Our results suggest increased atrial peak sodium current as a potential trigger for increased atrial excitability.

Alcohol abuse by patients undergoing methadone treatment programmes.

To study the prevalence of problem drinking among patients undergoing methadone treatment programmes, 170 patients were assessed using the self-administered alcohol screening test (mSAAST). Fifty-three (31.9%) patients scored 7 or more on the mSAAST, indicating actual or potential drinking problems. There was a slight tendency for these to be male. Patients who abused alcohol also tended to use benzodiazepines irrespective of sex. The results of the study seem to indicate that the prevalence of dual alcohol and opiate use is high amongst patients attending drug dependency units. Furthermore comprehensive research is required in order to plan effective treatment for these dual addicted patients.

Pinch-off syndrome: a complication of implantable subclavian venous access devices.

Implantable central venous access devices placed via the subclavian vein may become obstructed by thrombosis, impingement against a vein wall, or compression between the clavicle and first rib. The latter has been termed pinch-off syndrome (POS). Eleven patients with POS were studied, including one whose catheter had fractured and one whose catheter had fragmented. They were compared with 22 matched control patients and 100 consecutive routine clinic patients. Each catheter was graded: 0 = normal, 1 = abrupt change in course with no luminal narrowing, 2 = luminal narrowing, and 3 = complete catheter fracture. POS was present in most (eight of 11) cases within 3 weeks after placement. A grade 1 catheter was common (33%) among control subjects, but grades 2 and 3 were uncommon (1%). Catheter fracture or fragmentation was seen in two of five cases with long-term (greater than 3 weeks) pinching (grade 2 catheter). The following conclusions were reached: Grade 2 represents significant catheter compression and the potential for serious complications. Grade 1 is of uncertain clinical significance, due to its high prevalence in control subjects.

Inability of sonography to detect imminent ovulation.

Sonographic visualization of the cumulus oophorus or of morphologic alterations in the wall of the dominant follicle have been reported to be reliable signs of imminent ovulation when conventional transabdominal sonography is used. To determine if transvaginal sonography could allow a more frequent and confident prediction of imminent ovulation, we prospectively monitored 22 ovulatory menstrual cycles in four women undergoing artificial insemination and in 13 normally menstruating volunteers. Scanning was done on alternate days in the periovulatory period; a 7.5-MHz transvaginal transducer was used. Despite the improved resolution obtained with transvaginal sonography, confident identification of the cumulus oophorus or of mural changes in the follicle was not possible in any of the cycles followed. No other consistent follicular characteristic predicted imminent ovulation. We conclude that confident prediction of imminent ovulation is not possible with sonographic analysis.

Manganese intake and serum manganese concentration of human milk-fed and formula-fed infants.

Manganese (Mn) status was determined in 24 infants exclusively fed either human milk (n = 8) or formula (n = 16) from birth to 3 months. Mn intakes were estimated from test weighings , dietary records, and direct analyses of human milk and formula via graphite furnace atomic absorption spectrophotometry. Mean human milk Mn concentrations significantly decreased (p less than 0.05) with the progression of lactation, from 6.6 micrograms/L during the 1st month of lactation, to 3.5 micrograms/L by the 3rd month of lactation. Infant formulas were observed to contain considerably higher levels of Mn (70.0 to 1289.0 micrograms/L) than either human milk (means = 4.9 micrograms/L) or cows' milk (means 25.2 micrograms/L). At 3 months, human milk-fed infants consumed a smaller volume of milk (689.0 ml) than formula-fed infants (894.0 ml), and also received significantly less Mn (0.42 micrograms/kg/day) than formula-fed infants (183.22 micrograms/kg/day). Mean sera Mn concentrations of infants receiving human milk or formula were similar, with mean values of 4.4 and 4.7 micrograms/L, respectively. Manganese intakes of human milk-fed infants were found to be linearly correlated (r = 0.78) with the respective serum Mn concentration at 3 months of age.