Heart Rate Variability and Major Arrhythmic Events in Patients with Idiopathic Dilated Cardiomyopathy

This prospective study of 71 patients with idiopathic dilated cardiomyopathy (IDC) and preserved sinus rhythm was designed to evaluate the relation between heart rate variability (HRV) and subsequent major arrhythmic events. Standard time- and frequency-domain HRV parameters were obtained from analysis of 24-hour Holter ECG recordings. During a mean follow-up of 15 ± 5 months, major arrhythmic events including sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death occurred in 10 of the 71 study patients (14%). Neither time- nor frequency-domain indices of HRV differed significantly between patients with and patients without subsequent major arrhythmic events. However, there was a trend toward a lower standard deviation of the average normal RR interval for all 5-minute segments of the 24-hour recording (68 ± 17 ms vs 80 ± 31 ms; P = 0.06) in patients with major arrhythmic events. In addition, the percentage of adjacent normal RR intervals differing > 50 ms over the recording period tended to be lower in patients with major arrhythmic events (6%± 3% vs 9%± 6%; P = 0.08). Our results indicate a tendency toward attenuated parasympathetic activity in IDC patients with subsequent major arrhythmic events compared to arrhythmia-free patients. Larger studies with longer follow-up periods are necessary to clarify the role of HRV measurements for arrhythmia risk prediction in patients with IDC.     

Complications of Implantable Cardioverter Defibrillator Therapy: Follow-Up of 241 Patients

In order to determine the incidence of complications of impJantable cardioverter defibrillator (ICD) therapy, 241 patients with a total of 353 ICD implantations were followed for 24 ± 20 months. Complications were defined as any untoward effects experienced by the patient related to the ICD implantation and function or death within 4 weeks of implant or before hospital discharge. During follow-up, 129 of 241 patients (53%) had a total of 166 complications. An operative procedure was required to correct the complication in 50 of the 241 patients (21%). No patient died intraoperativeiy, but eight patients died within 4 weeks postoperatively or before hospital discharge. ICD infection required removal of the device in 13 patients (5%). Twenty-six patients (11%) had postoperative respiratory complications. Postoperative bleeding and/or thrombosis occurred in 11 patients (4%). Endocardial lead migration was observed in nine patients (4%) and lead adapter or insulation break occurred in nine patients (4%). Fifty-four patients (22%) experienced ECC-documented discharges for non-VT rhythm. In conclusion, although perioperative mortality in ICD patients is low, the maiority of patients have complications during followup. Recognition of these complications may allow for advances in ICD technology and management strategies to avoid their occurrence.     

Identification of defective binding of low density lipoprotein by the U937 proliferation assay in German patients with familial defective apolipoprotein B-100

Abstract. Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder characterized by decreased binding of low density lipoprotein (LDL) to the LDL receptor due to a substitution of glutamine for arginine in residue 3500 of apolipoprotein B-100. We present the results of the U937 cell proliferation assay for the detection of familial defective apo B100 in 13 German FDB patients. Due to a defect in the pathway of cholesterol synthesis the human myelomonocytic tumour cell line U937 lacks the ability to synthesize cholesterol which makes proliferation of these cells dependent on the presence of exogenous LDL-cholesterol. U937 cells were incubated with LDL from 13 FDB-patients, 10 healthy normocholesterolaemic individuals (NC) and 26 patients with familial hypercholesterolaemia due to a defective LDL-receptor (FH). At LDL-cholesterol concentrations below 1 μg ml^-1 no proliferation occurred. In the presence of LDL from FDB patients at concentrations between 2·5 μg ml^-1 and 15·0 μg ml^-1, the proliferation was significantly reduced compared to LDL from FH-patients and normocholesterolaemic controls. At 5 μg ml^-1 the reduction was 31–80% regardless of age, sex, apo E genotype, Lp (a)- and lipid levels. At concentrations above 25·0 μg ml^-1 no further differences were observed. The present results indicate that the U937 proliferation assay is a reliable test for the detection of defective LDL-binding due to the 3500 mutation in FDB patients. It may be useful for the detection of defective binding of LDL due to other mutations in the apo B-100 gene.     

PROGNOSTIC INFLUENCE OF p53 EXPRESSION IN GASTRIC CANCER

The presence of the nuclear phosphoprotein p53 was investigated in a series of 120 consecutive gastric carcinomas. This immunohistochemical study on formalin-fixed, paraffin-embedded material found p53 expression in 43 per cent ( n =51) of carcinomas using a monoclonal antibody (DO-1), whereas no immunoreactivity for p53 was present in tumour-associated non-neoplastic gastric mucosa or tumour stroma. There was no statistically significant correlation with known prognostic parameters such as extent of tumour growth (pT state), nodal involvement (pN state), or tumour grade. The same applied for association with patient age and sex or pathological parameters such as tumour size, localization, or growth pattern according to histological classification. Kaplan–Meier analysis revealed marginal statistically significant differences in survival times between patients with p53-positive tumours with more than 35 per cent of p53-positive tumour cells and those with less than 35 per cent of p53-positive tumour cells or p53-negative tumours ( P =0·04). However, by multivariate analysis, p53 immunoreactivity did not turn out as an independent prognostic parameter. p53 expression can easily be detected in a variety of human malignancies including gastric cancer by immunohistochemical methods, but its prognostic significance and possible role as an independent marker of poor prognosis still have to be confirmed by further studies.     

Hormonal regulation of lipogenesis in human diploid fibroblasts from normal subjects and from patients with familial hypertriglyceridaemia

Lipogenesis has been investigated in diploid fibroblasts derived from patients with familial hypertriglyceridaemia (FHT) and compared with cells from healthy persons. There was no difference in acetyl-CoA carboxylase activity in both cell types. Incorporation of [2-14C]-acetate into triglyceride fatty acids was slightly increased (34%) by the FHT lines. Addition of triiodothyronine caused a marked rise in [2-14C]-acetate incorporation by the FHT lines whereas the normal lines exhibited only control values. Maximal rise in [2-14C]-acetate incorporation was obtained with 5 micrograms/ml for 72 h. Under these conditions, acetate incorporation by the FHT lines was 220% of the controls, compared with 94% by the normal lines. Measurements of acetyl-CoA carboxylase specific activity supported the results obtained with measurements of acetate incorporation into triglyceride fatty acids. Individual FHT lines differ much in their quantitative answer to thyroid hormones, although the described effects were obtained with all eight lines under study. Insulin increased acetyl-CoA carboxylase activity and incorporation of [2-14C]-acetate in lipids in both cell types, but with no difference between normal and FHT lines. The results seem to reflect a higher lipogenic capacity of the hypertriglyceridaemic fibroblasts compared with normal cells.