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.     

Interactions between peroxisome proliferator-activated receptor-gamma 2 gene polymorphisms and size at birth on blood pressure and the use of antihypertensive medication

OBJECTIVE: The combination of small birth size and the Pro12Pro variant of the peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma 2) gene has been shown to be associated with insulin resistance, which is linked to hypertension. We examined whether the association between small body size at birth and adult blood pressure is modulated by PPAR-gamma 2 gene polymorphism, and whether the use of any class of antihypertensive medication is related to birth size. DESIGN AND METHODS: A total of 500 subjects from an original epidemiological cohort of 7086 men and women aged 65-75 years attended a clinical study. Two hundred and eight of them (73 men and 135 women) were taking antihypertensive medication and are included in this study. The Pro12Ala polymorphism of the PPAR-gamma 2 gene was determined using the polymerase chain reaction single-strand conformation polymorphism method. RESULTS AND CONCLUSIONS: Hypertensive subjects with low birth weight or short length at birth and the Pro12Pro variant had raised systolic blood pressure. We suggest that insulin resistance enhances the regulatory responses of the renin-angiotensin system, leading to raised blood pressure levels. Those hypertensive subjects who had small birth size and the Pro12Pro variant tended to use angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB). This could be because insulin resistance interacts with the renin-angiotensin system in ways that make ACEI/ARB an effective therapy. Alternative explanations include more severe and treatment resistant hypertension, leading to application of ACEI/ARB, or co-morbid conditions, such as myocardial infarction and type 2 diabetes, known to be linked to low birth weight.     

Changes in the histology and function of gastric mucosa and in Helicobacter pylori colonization during a long-term follow-up period after vagotomy in duodenal ulcer patients

BACKGROUND/AIMS: To investigate changes in the histology and the Helicobacter pylori (H. pylori) prevalence and density of the gastric mucosa, as well as in fasting serum gastrin and serum pepsinogen I, depending on completeness of vagotomy, and in cases of recurrent ulcer, during 14 years after operation in duodenal ulcer patients. METHODOLOGY: 122 vagotomized duodenal ulcer patients were studied twice on average 9 and 14 years after operation. The presence of recurrent ulcer and completeness of vagotomy were assessed simultaneously endoscopically and by endoscopic Congo red test. The histology of the gastric antrum and corpus mucosa was assessed in accordance with the Sydney system. The amount of H. pylori in the specimens was detected by microscopic counting; gastrin and pepsinogen I in serum were determined radioimmunologically. RESULTS: During the 14-year follow-up period, complete vagotomy patients were characterized by a smaller amount of active antrum gastritis and a larger amount of active chronic corpus gastritis involving corpus atrophy in 46% of cases 14 years after operation. Recurrent ulcer patients were characterized by a significantly higher prevalence of high-grade H. pylori colonization and active mucosal inflammation in the antrum as well as by a lower level of active mucosal inflammation and atrophy in the corpus and a higher serum pepsinogen I level compared with complete vagotomy cases. The data of incomplete vagotomy patients without recurrent ulcer became more similar to those recorded for recurrent ulcer patients. CONCLUSIONS: In duodenal ulcer patients, changes in the histology of the gastric antrum and corpus mucosa as well as in H. pylori prevalence and density and in serum pepsinogen I levels are different depending on completeness of vagotomy during 14 years after operation.     

Provocation of ventricular tachycardia by antimalarial drug halofantrine in congenital long QT syndrome

This report deals with two patients who suffered sustained episodes of torsade de pointes ventricular tachycardia while using the novel antimalarial drug halofantrine. Both patients had congenital long QT syndrome, and their QT interval was further prolonged at the time of the event. This first electrocardiographic documentation of ventricular arrhythmias together with halofantrine's known prolonging effect on the QT interval demonstrates that the drug has the potential to induce life-threatening arrhythmias.     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Antibodies to human heat shock protein 60, hypertension and dyslipidemia. A study of joint effects on coronary risk

OBJECTIVE: High IgA-class (but not IgG-class) Anti-Heat-shock-protein 60 antibody level is a predictor of coronary risk in dyslipidemic middle-aged men. In this paper we studied the joint effects of high Anti-Hsp60-antibody level and the classical coronary risk factors. METHODS: We used nested case-control design and logistic regression analyses. The cases consisted of 233 middle-aged men with myocardial infarction or coronary death during 8.5-year follow-up in Helsinki Heart Study, a coronary primary prevention study with gemfibrozil. The controls were subjects without coronary events, matched for drug treatment and the geographical area. RESULTS: The relative coronary risks (Odds Ratios (ORs); 95% confidence interval) were 1.41 (0.96-2.05) for high IgA-class Anti-Hsp60 antibody level and 1.98 (1.35-2.90) for hypertension, defined as mean arterial pressure >114 mmHg. With simultaneous occurrence of high Anti-Hsp60 antibody level and hypertension, the ORs were 2.32 (1.26-4.27) for systolic and 2.99 (1.63-5.48) for diastolic hypertension. Similar patterns of joint effects were found between high Anti-Hsp60 antibody and lipoprotein cholesterol levels as well as antibodies against oxidized low-density lipoprotein. CONCLUSIONS: Our results suggest that, while high IgA-class Anti-Hsp60 antibody level predicts coronary risk, the effect is modest without simultaneous occurrence of other classical risk factors.     

Acute sinusitis: Finnish clinical practice guidelines

These clinical practice guidelines aim at providing assistance mainly to primary health care physicians for the diagnosis and management of acute sinusitis. Despite the huge impact of upper respiratory infections, criteria for diagnoses are often vague, and physicians are often uncertain of their diagnoses. This is not surprising, as the sole definition of acute sinusitis is somewhat confusing, not to mention the existing discrepancies between treatments, even among specialists. The Finnish Society of Otorhinolaryngology has set up a committee to evaluate existing data on acute sinusitis and to formulate these guidelines. The committee comprised Finnish experts in adult and paediatric otorhinolaryngology, clinical microbiology, radiology, paediatrics, and epidemiology. Recommendations given are based on the principles of evidence-based medicine, with the level of evidence presented.     

Is there any link between insulin resistance and inflammation in established preeclampsia?

Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia.     

Laminin isoforms in fetal and adult human adrenal cortex

Laminin has been proposed to influence the function of human adrenal cortex. We have studied the distribution of laminin (Ln) chains using immunofluorescence in human fetal and adult adrenal cortex. In the fetal gland Ln alpha2- and alpha5-chains were weakly expressed in the definitive zone, whereas Ln alpha4-, beta1-, and gamma1-chains occurred around vessels. In the adult gland, Ln alpha2-, alpha5-, and gamma1-chains were found in epithelial basement membranes (BM) in all cortical zones, Ln alpha4-chain in vessels, Ln beta1-chain in outer zone, and Ln beta2-chain in the two inner zones of the cortex, respectively. Among the integrins in adult gland, integrin alpha(3)-subunit was confined to basal surfaces of cortical cells, alpha(6) to vessels, alpha(1) to the stroma, and alpha(2) diffusely to epithelial cells. Lutheran glycoprotein and dystroglycan occurred in the fetal gland diffusely in the definitive zone and throughout the epithelium in the adult. The isoform composition of BM of the adult adrenal gland is distinct, with Ln-2 and -10 in BM of the outer zone and Ln-4 and -11 in BM of the two inner zones. The results suggest that integrin alpha(3)beta(1) and Lutheran are candidate receptors for Ln-10 and -11, whereas dystroglycan probably binds Ln-2 and -4.