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Biomedical subjects

E Rosenthal

Publications and source records attributed to E Rosenthal.

At least 163 records · Page 9Linked to original sources

The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders.

The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function.

Binding Sites↗

Laser thermal angioplasty probe ("hot tip") temperature: effects of flow.

The temperature developed by the laser thermal ("hot tip") probe during arterial recanalisation is primarily dependent on the rate of energy delivery and the rate of dissipation to the surrounding medium. While higher probe tip temperatures enhance the efficacy of atheroma ablation, so too is the incidence of adverse effects increased. We studied the temperature developed in the probe tip in an artificial circulation using both saline and blood. In saline the peak probe temperatures were limited to 100 degrees C (boiling point), falling with each increment in flow. Small discrepancies in probes at different times and may be due to malalignment of the optical fibre-metal cap coupling, temperature measurement inaccuracy, tip insulation, or generator output instability. In blood, charring and clot formation insulated the tip raising the temperature (up to 700 degrees C within 5 seconds at 10 W) but also retarded dissipation of heat to the surroundings. The degree of clot and char formation was critical in determining subsequent thermal responses in any particular probe. The unknown rate and quantity of char buildup and changing blood flow during in vivo angioplasty are likely to be important obstacles to developing a reliable thermal feedback control system.

Angioplasty, Balloon↗

Characterization of 1,4, dihydropyridine calcium channel binding sites in the human prostate.

The binding and functional properties of calcium channel receptors have not been previously characterized in the normal or hyperplastic prostate. Dihydropyridine (DHP) binding sites have been characterized in other tissues using the ligands 3H-nitrendipene and (+)3H-PN200-110. Saturation experiments were performed on homogenates obtained from five human prostate adenomas using these ligands. The binding of 3H-nitrendipine and (+)3H-PN200-110 in the prostate was saturable and of high affinity. The mean Kd of 3H-nitrendipine and (+)3H-PN200-110 was 0.92 +/- 0.11 nM and 0.14 +/- 0.02 nM, respectively. The mean Bmax of 3H-nitrendipine and (+)3H-PN200-110 was 0.57 +/- 0.06 and 0.19 +/- 0.02 fmol/mg. wet wt., respectively. The percent specific binding of 3H-nitrendipene and (+)3H-PN200-110 was 18 +/- 1% and 38 +/- 4%, respectively. The pharmacology of (+)3H-PN200-110 binding sites was further characterized using competition displacement experiments. The IC50 corrected values for Bay K 8644, nifedipine, verapamil, and diltiazem in the human prostate and other tissues are of the same order of magnitude. The prostate contains an abundance of high affinity DHP binding sites. The physiologic significance of the DHP binding sites in the prostate requires further investigation.

Binding Sites↗

Normal and stenotic human aortic valve opening: in vitro assessment of orifice area changes with flow.

The ability to measure aortic valve area clinically has emphasized the need to understand the changes in aortic valve orifice area during flow. To compare the performance of normal and stenotic human aortic valves we used a pulsatile flow model that simulated in vivo flow conditions. Five normal autopsy specimens and 15 stenotic valves removed at operation were mounted into the model. Valve function was assessed by analysis of video recordings of valve leaflet motion during flow. Over the flow rates tested normal valves demonstrated a linear increase in orifice area. There was no resistance to leaflet opening and valve closure was rapid. The majority of stenotic valves demonstrated an increase in orifice area at low flow rates. No valve showed any increase in maximal area beyond flow rates of 3 l min-1. Increased leaflet resistance of these abnormal valves resulted in notably slower opening and closing rates. In patients with a high cardiac output and severe stenosis, overestimation of the anatomic orifice area derived by the Gorlin equation can result. This is not related to variability in maximal orifice area.

Aortic Valve↗

In vitro measurement of stenotic human aortic valve orifice area in a pulsatile flow model. Validation of the continuity equation.

Aortic valve orifice area estimation in patients with aortic stenosis may be obtained non-invasively using several Doppler echocardiographic methods. Their validity has been established by correlation with catheterization data using the Gorlin formula, with its inherent limitations, and small discrepancies between the methods are present. To evaluate these differences further, 15 patients with severe aortic stenosis (mean transvalvular gradient 70, range 40-130 mmHg) had aortic valve area estimations by Doppler echocardiography using two variations of the continuity equation. The intact valves removed at valve replacement surgery were then mounted in a pulsatile model and the anatomical area was measured (mean 0.67 +/- 0.17 cm-2) from video recordings during flow at 5.4 l min-1. Aortic valve area calculated using the integrals of the velocity-time curves measured at the left ventricular outflow tract and aortic jet (mean 0.65 +/- 0.17 cm2) correlated best with the anatomical area (r = 0.87, P less than 0.001). The area derived by using the ratio of maximum velocities from the left ventricular outflow tract and aortic jet (mean 0.69 +/- 0.18 cm2) also correlated well with the anatomical area (r = 0.79, P less than 0.001). The index between the left ventricular outflow tract and aortic jet maximum velocities was less than or equal to 0.25 in all. In patients with severe aortic stenosis the aortic valve area can be reliably estimated using Doppler echocardiography.

Adult↗

Serum lipoprotein profile in children with celiac disease.

Jejunal mucosa is responsible for the absorption of triglycerides and the production of lipoproteins [chylomicrons, very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL)] and apolipoproteins (B-48, A-I, A-II, A-IV, C-II). Mucosal damage is known to cause fat malabsorption and probably also affects the serum lipid profile. To determine lipoprotein production in states of enterocyte dysfunction, we compared the serum lipid profiles in a group of 12 children with untreated celiac disease (flat jejunal mucosa) with the profiles in a control group of 10 children suffering from other intestinal diseases. Statistically significant differences were found in the following parameters (celiac versus control): plasma levels of triglycerides (70 versus 119 mg/dl), cholesterol content in LDL (107 versus 67.7 mg/dl), protein content in VLDL (6 versus 10 mg/dl), and level of apoprotein A-I (112 versus 140 mg/dl). No significant differences were found between the two groups in the serum levels of total cholesterol, the cholesterol content in VLDL and HDL, the protein content in LDL and HDL, and the level of apoprotein B. Following institution of a gluten-free diet, the lipoprotein profile reverted to normal. These data suggest that the changes in the serum lipoprotein profile in celiac disease are secondary to alterations in enterocyte function and not only a reflection of fat malabsorption.

Celiac Disease↗

Balloon dilatation of the aortic valve in a pulsatile flow model: assessment of the mechanisms and the magnitude and duration of changes in valve area and gradient.

Eighteen stenotic aortic valves (17 removed at operation) mounted in a pulsatile flow duplicator were dilated with a balloon catheter. Sequential measurements showed that the valve area initially increased from a mean (SD) of 0.52 (0.16) to 0.78 (0.17) cm2. It was 0.73 (0.16) cm2 five minutes after dilatation and this was little changed at four weeks (0.70 (0.15) cm2). Initially the mean transvalvar gradient fell significantly from 54 (27) to 32 (8) mm Hg but increased to 35 (10) mm Hg at five minutes and to 40 (11) mm Hg at four weeks. In six valves stretching of the orifice was the only mechanism responsible for the changes while in the remainder there was tearing through commissures with a greater initial increase in area (0.31 v 0.18 cm2) and a smaller decrease in area at five minutes (0.03 v 0.08 cm2). Fractures of calcific deposits in non-commissural positions were seen in one valve only. This laboratory study of isolated aortic valves showed a significant but small increase in valve area after balloon dilatation, which was greater when commissural tearing had occurred. Recoil of the stretched orifice was complete at five minutes and there was little further change over the next four weeks.

Adult↗

Thermal effects of stationary "hot tip" laser coronary probes: an in vitro assessment.

Percutaneous laser thermal probe angioplasty requires sufficient laser probe flexibility to access the coronary tree. This may entail a loss of axial strength and the resultant slow advancement may lead to unwanted heating of the normal coronary artery proximal to the lesion. To assess the lateral thermal effects of stationary coronary laser probes, laser thermal energy (50-150 J) was delivered to 25 coronary artery segments (diameter 1.9-4.0 mm) in a perfused cadaver heart preparation using a 1.7 mm tip probe. Adherence to the vessel wall occurred in 19 segments, endothelial charring in 8 segments, and perforation in 3 segments. Endothelial charring was seen in 8 of 13 nonperfused segments but in 0 of 12 segments perfused at 60 ml/minute (P less than 0.01). In all three perforations the vessel to probe diameter ratio was less than 1.6:1, perfusion was absent, and traction to dislodge the adherent probe was necessary. Lateral wall damage is a complication of stationary laser probes: smaller-tipped probes which are advanced rapidly at the time of energy delivery may enhance the safety margins of coronary laser thermal probe angioplasty.

Angioplasty, Balloon↗

A pharmacokinetic study of cilazapril in patients with congestive heart failure.

1. The pharmacokinetics of cilazapril and the inhibition of angiotensin converting enzyme (ACE) were investigated in 10 patients with congestive heart failure, NYHA class II-III, receiving diuretics with or without digoxin. 2. Patients received 0.5 mg and 1 mg cilazapril on the first 2 days, followed by 0.5 mg or 1 mg daily for the next 8 weeks, in a single-blind study. Plasma cilazaprilat concentrations and plasma ACE activities were measured by radioenzymatic methods up to 24 h after the first and last doses. 3. After the initial 0.5 mg dose of cilazapril, a mean maximum plasma concentration of cilazaprilat of 6.8 ng ml-1 was observed at 2.3 h. Concentrations declined up to 8 h with a mean half-life of 5.8 h, followed by slower decrease to 24 h. Total clearance, based on data to 24 h, was estimated at 8.5 l h-1, with three-fold inter-individual variation. Mean maximum plasma ACE inhibition was 87%, decreasing to 65% at 24 h. 4. In the multiple dose phase of the study, four patients received cilazapril 0.5 mg daily, and six patients 1 mg daily. Cilazapril accumulation for the 0.5 mg group averaged 77%, but steady state concentrations for the 1 mg group were less than double those of the 0.5 mg group. ACE inhibition profiles at steady state were similar for both groups, and they differed from first dose data only in a somewhat lower inhibition at 24 h. 5. Historical comparison of the first-dose data with those for healthy young volunteers at identical dosage revealed only minor differences in kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

His bundle ablation with the laser thermal probe ("hot tip"): a feasibility study.

Successful percutaneous ablation of the bundle of His requires accurate localization together with delivery of the minimum effective energy to avoid unwanted effects. The energy output from laser sources can be controlled very precisely but is not easily directed to the bundle of His using conventional fiber optics. The laser thermal probe ("hot tip") consists of an optical fiber and a terminal metal cap that is rapidly heated during energy delivery. When applied to cadaver hearts at energies of 100-150 joules (10 watts for 10-15 seconds) the 2.0-mm diameter peripheral artery probe was able to damage the bundle of His without extensive surrounding damage. The right ventricular free wall and interventricular septum were perforated during some applications at these energies leaving a tract with a diameter of less than 2.0 mm. The atrioventricular (AV) membranous septum, Foramen Ovale, right atrial appendage, and septal leaflet of the tricuspid valve were more resistant at these energy levels and perforations were always less than 1.0 mm in diameter. The probe was modified for use during electrophysiological studies and good quality unipolar electrograms were recorded from the metal cap confirming that the probe could be accurately positioned adjacent to the bundle of His. The laser thermal probe deserves further study as a "self directing" ablation tool.

Arrhythmias, Cardiac↗

Comparison of isradipine and nifedipine in chronic stable angina.

Isradipine, a new dihydropyridine calcium antagonist, was compared to nifedipine in the treatment of 11 male patients with angina and coronary artery disease in a randomised, double-blind cross-over study. Patients received 5 mg nifedipine three times a day rising to 20 mg three times a day in three dosage increments over six weeks or 2.5 mg isradipine three times a day rising to 7.5 mg three times a day in three dosage increments over six weeks, and then received the alternate preparation. There were no significant differences between the drugs in terms of the frequency and severity of angina attacks or the consumption of glyceryl trinitrate. The increases in systolic blood pressure and the double product during exercise were significantly less with isradipine than with nifedipine. There was a similar trend in heart rates. There was no difference between the treatments in respect of exercise induced ST-segment depression or diastolic blood pressure. We conclude that isradipine and nifedipine have similar anti-anginal effects and that isradipine may be a useful new anti-anginal agent.

Aged↗