Cardiac arrest and left ventricular fibrosis in a Finnish family with the lamin A/C mutation

Introduction: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms.
Methods and Results: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum.
Conclusion: These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.     

Late QRS Activity in Signal‐Averaged Magnetocardiography,Body Surface Potential Mapping,and Orthogonal ECG in Postinfarction Ventricular Tachycardia Patients

Background: Delayed electrical activity necessary for re‐entrant ventricular tachycardia (VT) is detectable noninvasively with high resolution techniques. We compared high resolution signalaveraged analysis of magnetocardiography (MCG), body surface potential mapping (BSPM), and orthogonal three‐lead ECG (SA‐ECG) in the identification of patients prone to VT after myocardial infarction (Ml). Methods: Patients with remote myocardial infarction and cardiac dysfunction were studied, 22 with (VT group) and 22 without VT (control group). MCG with seven channels and BSPM with 63 and SA‐ECG with three orthogonal leads were registered. After signal‐averaging and highpass filtering, three time domain analysis (TDA) parameters describing late electrical activity were computed: QRS duration (QRSd), root mean square amplitude (RMS) of the last 40 ms of QRS, and the duration of the low‐amplitude QRS end (LAS). Results: All parameters by each method were significantly different between the patients’groups. For example, LAS parameter in MCG was 59 (SD 22) ms in the VT group vs. 37 (SD 13) ms in controls (P < 0.001), 77 (SD 22) ms vs. 56 (SD 19) ms in BSPM (P = 0.002), and 60 (SD 24) ms vs. 39 (SD 22) ms in SA‐ECG (P = 0.005). The combination of LAS parameter in MCG and SA‐ECG resulted in improved performance in comparison to any single parameter with 95% sensitivity and 68% specificity. Conclusions: All three high resolution methods identified VT propensity among post‐Mi patients with cardiac dysfunction and between‐method differences were small. Information in MCG and SA‐ECG may be complementary and their combination could be of value in postinfarction arrhythmia risk assessment. A.N.E. 2002;7(4):389–398     

Spontaneous rupture of a hepatic cystadenoma and cystadenocarcinoma: report of two cases

Hepatobiliary cystadenomas and cystadenocarcinomas are rare tumors. Differentiating between these tumors and benign hepatic cysts may be difficult. Because of their rarity, diagnosis is often delayed and may result in inaccurate treatment, resulting in unnecessary morbidity and mortality. The purpose of this report is to draw attention to these entities and their complications. We report on two cases with spontaneous rupture of hepatobiliary cystadenoma and cystadenocarcinoma cysts, initially treated as simple hepatic cysts by aspiration, or by aspiration combined with sclerotherapy. The spontaneous rupture of the cysts appeared years after the initial treatment of the cysts, leading in one case to a prolonged stay in an intensive care unit. In both cases, a formal liver resection was carried out and microscopic investigations revealed a mucinous cystadenocarcinoma and cystadenoma. In conclusion, although hepatobiliary cystadenomas and cystadenocarcinomas are rare findings, they should not be forgotten in the diagnostic workshop when examining patients with hepatic cysts. If hepatobiliary cystadenomas and cystadenocarcinomas cannot be excluded following radiological imaging, surgery is recommended.     

The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity

Aims

Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).

Methods

In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day⁻¹ (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.

Results

Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.

Conclusions

The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.     

Fractal correlation properties of R-R interval dynamics in asymptomatic relatives of patients with dilated cardiomyopathy

BACKGROUND AND AIM: asymptomatic relatives of patients with familial dilated cardiomyopathy who have left ventricular enlargement [LVE] are at risk for progression to dilated cardiomyopathy. A novel index of the fractal correlation properties of heart rate variability (HRV), the short-term scaling component (proportional, variant(1)) in detrended fluctuation analysis, is a promising prognostic tool in left ventricular dysfunction. The aim of this study was to compare values of proportional, variant(1) and conventional HRV indices in LVE relatives with dilated cardiomyopathy patients and normal controls. METHODS: time-domain and spectral HRV measures, and the short-term scaling component ( proportional, variant(1)) were assessed from 24-h Holter recordings from 22 LVE relatives (left ventricular end-diastolic dimension >112% predicted, normal fractional shortening), 24 dilated cardiomyopathy patients and 14 controls. RESULTS: the time domain index SDNN was lower in dilated cardiomyopathy patients [101.8(+/-44.0)] than in LVE relatives [161.7(+/-53.9)] or controls [152.9(+/-51.4)], P=0.01. Similarly, triangular index and spectral measures were reduced in dilated cardiomyopathy patients but not in LVE relatives or controls. In contrast, the short term scaling component ( proportional, variant(1)) in detrended fluctuation analysis was reduced in both dilated cardiomyopathy patients [1.06(+/-0.33)] and in LVE relatives [1.15 (+/-0.20)], compared with controls [1.32(+/-0.16)], P=0.01. Among DCM patients the short-term scaling component ( proportional, variant(1)) was significantly associated with echocardiographic deterioration during follow-up (3.7+/-2.1 year) (P=0.004). CONCLUSION: the short-term scaling component ( proportional, variant(1)) is reduced in asymptomatic relatives of dilated cardiomyopathy patients who have LVE.     

Autoimmune response in mothers of children with congenital and postnatally diagnosed isolated heart block: a population based study

OBJECTIVE: To study the autoimmune response in mothers of children with isolated congenital heart block (CHB) and heart block (HB) diagnosed postnatally. METHODS: We reviewed the Finnish hospital registries for patients born between 1950 and 2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and sera for the determination of autoantibodies were available from 67 mothers of children with CHB and from 37 mothers of children with postnatally diagnosed HB 9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time-resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker antibodies for connective tissue diseases (CTD) were determined by immunoblot and/or by immunofluorescence. The control group comprised 136 mothers with primary Sj?gren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD with healthy children. RESULTS: Sixty of our 67 mothers (90%) of children with CHB had antibodies to SSA or SSB by the methods initially used in this study. When retests and tests performed previously were taken into account, only 3 (4%) of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%) had any autoantibodies. Increased risk of having a child with CHB was indicated by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays, whereas low risk was indicated by maternal SLE or other CTD and undetectable or low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly superior to others, but in general, immunoblots were more specific than TR-FIA. CONCLUSION: Maternal autoimmune disorder is almost always associated with CHB but only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker antibodies for mothers of children with CHB, and an increased risk of having an affected child is indicated by maternal primary SS and high titer antibodies to SSA and SSB.     

Persistence of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a 20-year follow-up

BACKGROUND: The persistence of antibodies against measles, mumps, and rubella induced by the measles-mumps-rubella (MMR) vaccine and the kinetics of antibody decline after the second MMR vaccine dose were studied in the same cohort for 20 years. METHODS: Measles, mumps, and rubella antibodies were measured by enzyme immunoassay in 20-year follow-up serum samples (n= 183) of twice-vaccinated individuals, and measles antibodies were also measured in oral fluids (n = 177). Antibody decay was determined in a group (n = 58) with subsequent samples collected 1, 8, and 15 years after the second MMR dose. RESULTS: In total, 95%, 74%, and 100% of 183 vaccinees were still seropositive for measles, mumps, and rubella, respectively, and 85% of 177 vaccinees had measurable measles antibodies in their oral fluids. The antibody levels declined significantly after the second dose, but subsequently the rate of decline was slower. CONCLUSIONS: A high rate of seropositivity was found 20 years after the first MMR dose, particularly for rubella and measles. Our results show that MMR vaccine-induced antibodies wane significantly after the second dose. According to epidemiological data, the protection induced by MMR vaccination in Finland seems to persist at least until early adulthood. However, the situation requires constant vigilance.