Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer.

Vascular endothelial growth factor (VEGF) has been shown to stimulate angiogenesis and myocardial perfusion. The short-term safety of VEGF gene therapy is excellent. However, there are only limited results regarding the long-term effects. The Kuopio Angiogenesis Trial (KAT) studied the efficiency and short-term safety of the local VEGF-A(165) gene transfer in 103 patients with coronary artery disease. Three patient groups received either VEGF as an adenoviral (n=37), or as a plasmid/liposome vector (n=28), or as a placebo (n=38), during coronary angioplasty and stenting (percutaneous coronary intervention, PCI)AQ1. The aim of this study was to examine the long-term effects and safety of VEGF gene therapy. Patients were interviewed by telephone or with a questionnaire on their current status of health, coronary and other cardiovascular events and symptoms, working ability, exercise tolerance, other diseases, such as cancer and diabetes, as well as their personal experience of the treatment. Causes of death were clarified from hospital records. The total follow-up time was 8.1 years (range 6.9-9.7 years). Overall 82% of the patients were reached across the study. Eight (7.5%) of the patients died during the follow-up, but there was no significant difference in mortality between the groups (3/32 vs 2/26 vs 3/31 VEGF-adenovirus vs VEGF-plasmid/liposome vs placebo, respectively; P=0.88). The incidence of major adverse cardiovascular events (MACEs) (10 vs 11 vs 15; P=0.85), cancer (1 vs 4 vs 2; P=0.38) or diabetes (2 vs 2 vs 2; P=0.97) did not differ between the groups. Local intracoronary VEGF gene transfer is safe and does not increase the risk of MACE, arrhythmias, cancer, diabetes or other diseases.

Extensive variation in the signal amplitude of the atrial floating VDD pacing electrode.

The dependence of atrial signal amplitude on the site of the atrial sensing dipole of a single-pass lead was examined in 29 patients. The vertical location of the dipole was documented in supine fluoroscopy during quiescent and deep breathing and in upright chest roentgenogram, and was expressed as a proportion of the right atrial height. As the group average, the atrial signal amplitude was equal when tested in supine, sitting, standing, and right- or left-side positions in follow-up determinations. The signal amplitude varied markedly between postures, showing a coefficient of variation of 45% +/- 24% within the group. Coefficient of variation within the 6-month follow-up period in each tested position ranged from 31%-44%. Correlation between postures was weak (range of r = 0.53-0.81). Vertical location of the atrial dipole had no relationship to the signal amplitude. At least in one posture or test occasion the atrial signal amplitude was very low, < or = 0.35 mV in 20 patients, and below detection limit (0.25 mV) in 5 patients. Programmed to high sensitivity, atrial undersensing was rare in ambulatory electrocardiography, ranging from 0-9,000 missed atrial beats (0%-8%), with a median of 100 beats/24 hours. In conclusion, temporary variation in atrial signal amplitude is extensive. Despite occasionally measured large signal amplitudes atrial sensitivity in single lead VDD pacemakers should be programmed high, and if poor atrial tracking is suspected, other methods besides routine sensitivity testing should be adapted.

Heart rate and blood pressure variability and baroreflex sensitivity in hypercholesterolaemia.

To evaluate cardiovascular autonomic function in hypercholesterolaemia, we studied 16 age-matched pairs of healthy males with elevated serum cholesterol and normocholesterolaemic control subjects (altogether 37 men, aged 27-56 years). We used power spectral analysis to measure short-term heart rate and blood pressure variability, and the phenylephrine method to determine baroreceptor reflex sensitivity. The mean (SD) serum cholesterol concentration was 6.43 (1.22) among the hypercholesterolaemic subjects and 4.30 (0.44) mmol/l among the control men (P < 0.001). The respective low density lipoprotein (LDL) cholesterol concentrations were 4.44 (1.22) and 2.46 (0.38) mmol/l (P < 0.001). The total power (0.0-0.5 Hz) of heart rate and blood pressure variability did not differ between the groups, and neither did the high-frequency (0.15-0.5 Hz) and medium-frequency components (0.07-0.15 Hz). Mean (SD) baroreceptor reflex sensitivity was 18.1 (7.9) in hypercholesterolaemic and 19.4 (6.3) ms mmHg-1 in normocholesterolaemic subjects (P = 0.352). when all the subjects were analysed together, we observed a slight inverse trend between serum LDL cholesterol and baroreceptor reflex sensitivity (r = -0.235, P = 0.161). In conclusion, hypercholesterolaemia does not alter autonomic neural regulation of the cardiovascular system as assessed heart rate and blood pressure variability and baroreflex sensitivity.

Variables affecting the drill-generated noise levels in ear surgery.

The manner in which the variables rotation speed, type of burr, burr size and site of drilling influence bone-conducted, drill-generated noise levels in ear surgery, has been investigated. From the results obtained, the following conclusions can be drawn. 1. The noise levels were primarily influenced by the size of the burr. The 6 mm cutting burrs gave a noise level of 88-108 dB, the use of a 4 mm one resulted in a reduction of 1-6 dB and the use of a 2 mm one, 5-16 dB. The mean noise levels of the diamond burrs were 5-11 dB lower than the mean noise levels of the cutting ones. 2. Variations in rotation speed had only a slight influence on the noise levels produced (0-5 dB). 3. Three different types of cutting burr were tested. All gave noise levels of about the same order of magnitude. 4. The noise levels around the cochlea were only slightly influenced by the localization of the drilling within the ear (less than 1.8 dB). 5. Drill-induced noise levels in ear surgery cannot be reduced to any great extent. Possible noise traumas to the inner ear can only be avoided by minimizing the duration of drilling and thus, the duration of harmful noise exposure to the cochlea.