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Biomedical subjects

C Storm

Publications and source records attributed to C Storm.

9 recordsLinked to original sources

Changes in cardiac function at rest before and after treatment in primary hypothyroidism.

The aim of the present study was to investigate in hypothyroid patients the reversibility of the prolongation of electromechanical delay and of the impairment of early diastolic relaxation as measured by radionuclide ventriculography after restoration of euthyroidism. We also evaluated Doppler echocardiography in relation to scintigraphic findings. Twenty-six consecutive hypothyroid patients were studied at diagnosis and after treatment. The time to peak ejection decreased (161 +/- 6 vs 145 +/- 5 ms; p = 0.03) without changes in global systolic function (ejection fraction). The peak filling rate was reversible as well: 2.6 +/- 0.1 versus 3.0 +/- 0.2 end-diastolic volume/s; p = 0.003. No significant changes in systolic and diastolic cardiac function or ventricular geometry were detected by Doppler echocardiography. However, subanalysis of profoundly hypothyroid patients (free T4 < 4.5 pmol/L, n = 8) revealed a decrease in the septal wall thickness (9.9 +/- 0.7 vs 8.3 +/- 0.4 mm, p = 0.01) and increases in early peak transmitral inflow velocity (53 +/- 4 vs 65 +/- 4 cm/s, p = 0.03), as well as left ventricular end-diastolic diameter (4.8 +/- 0.1 vs 5.1 +/- 0.2 cm, p < 0.05) after treatment. Thus, in primary hypothyroidism, a subtle reversible prolongation of contraction without major changes in global systolic function and a decrease in early active relaxation is observed by radionuclide ventriculography. Echocardiography shows changes only in severely hypothyroid patients.

Adolescent↗

Heparin-coated circuits reduce occult myocardial damage during CPB: a randomized, single blind clinical trial.

OBJECTIVES: Cardiopulmonary bypass is associated with a diffuse systemic inflammatory response that can cause considerable morbidity, including organ dysfunction and bleeding. Heparin-coated circuits have been shown to give a reduced inflammatory response with clinical benefits during open-heart surgery. However, the effects on lipid peroxidation, neutrophil activation and myocardial ischemic damage in the human have remained unknown. METHODS: In a randomized single blind trial, complement activation, neutrophil counts, malondialdehyde, and cardiac enzymes were studied in 39 patients undergoing open-heart surgery. Two groups were perfused with cardiopulmonary bypass circuits with (n=20) or without heparin-coating (n=19). RESULTS: The different complement factors (C3, C4, C3d, C3d/C3 and the C-function), neutrophil levels, MDA and the cardiac enzyme levels were comparable before CPB was started and significantly increased in both groups during bypass. There were significant intergroup differences in the neutrophil levels and MDA after reperfusion (P<0.0001). Furthermore, significant positive correlations between the lipid peroxidation, expressed as MDA levels, and the levels of neutrofils and the cardiac enzyme, CK-MB were seen within the groups. CONCLUSIONS: Heparin coated circuits did lead to a decreased neutrophil response and MDA level. The correlations between CK-MB and neutrophil and MDA levels suggest neutrophil activation leading to lipid peroxidation that may influence myocardial damage. Heparin coating improved biocompatibility and was associated with less occult myocardial ischemic damage in patients undergoing open heart surgery.

Aged↗

Universal algebraic relaxation of velocity and phase in pulled fronts generating periodic or chaotic states

We investigate the asymptotic relaxation of so-called pulled fronts propagating into an unstable state, and generalize the universal algebraic velocity relaxation of uniformly translating fronts to fronts that generate periodic or even chaotic states. A surprising feature is that such fronts also exhibit a universal algebraic phase relaxation. For fronts that generate a periodic state, like those in the Swift-Hohenberg equation or in a Rayleigh-Benard experiment, this implies an algebraically slow relaxation of the pattern wavelength just behind the front, which should be experimentally testable.

Journal Article↗

Improved blood cellular biocompatibility with heparin coated circuits during cardiopulmonary bypass.

BACKGROUND: The clinical use of heparinized surfaces in the extracorporeal circuit was studied to find out if there was any blood cell rheologic benefit to support its use in routine low risk cardiac surgery. METHODS: In a prospective single blind study, 39 patients were operated upon with the heart lung machine for angina pectoris by coronary bypass grafting and were randomized to a control group or a heparin group. Blood cell rheology was analysed using the St. George filtrometer where damage to the red blood cells and white blood cells was estimated by assessing deformability reductions, transit, time increases and clogging rate and clogging particle changes. RESULTS: At the end of cardiopulmonary bypass, in the heparin group, the red cell filterability (rFR) and the white cell filterability (WFR) were 8% better than in the control group (p=0.0079 and p=0.027 respectively). The red cell transit time was 19% slower in the control group (p=0.0351). The red cell clogging rate (RCR) and clogging particles (RCP) were significantly lower in the heparin group (p=0.0212 and p=0.0409 respectively. The white cell clogging rate (WCR) and clogging particles (WCP) showed a similar pattern. CONCLUSIONS: In spite of these significant differences the clinical outcome was similar in the groups. Thus heparin coating of the extracorporeal circuit reduces blood cell rheologic damage significantly in low risk patients undergoing routine bypass surgery for angina but this use did not lead to any clinical benefit postoperatively. Therefore the use of such circuits for routine low risk cardiac surgery cannot be recommended.

Aged↗

Cardiac function at rest in hypothyroidism evaluated by equilibrium radionuclide angiography.

OBJECTIVE: Previous studies have suggested that hypothyroidism affects both systolic and diastolic cardiac function. We have applied equilibrium radionuclide angiography to the study of heart function at rest in hypothyroidism. DESIGN: A prospective study, evaluating cardiac function at rest in primary hypothyroidism. METHODS: Cardiac function was studied by means of equilibrium radionuclide angiography. Screening echo-Doppler examinations were performed on each patient. PATIENTS: Twenty-six consecutive untreated hypothyroid patients without clinical or echocardiographic cardiac disease and 20 healthy matched controls. RESULTS: Between patients and controls, the time to peak emptying rate (161 +/- 6 msec vs. 144 +/- 6 msec, P < 0.05) and the time to peak filling rate (188 +/- 6 msec vs. 170 +/- 5 msec, P < 0.05), were the only discriminatory parameters. In hypothyroid patients, a trend towards a decrease in diastolic cardiac function, expressed as peak filling rate, was observed: 2.6 +/- 0.1 End Diastolic Volume (EDV)/s vs. 3.0 +/- 0.1 EDV/s, P = 0.06. Within the hypothyroid patient group, the time to peak emptying rate was more prolonged in patients with lower free thyroxine levels (R = -0.60, F = 13.5, P < 0.001). Peak filling rate was decreased in patients with lower free thyroxine levels (R = 0.51, F = 8.4, P < 0.01) whereas the time to peak filling rate was more prolonged (R = -0.62, F = 15, P < 0.001). CONCLUSION: In a large group of consecutive patients presenting with primary hypothyroidism, even in the absence of clinical cardiac disease and echocardiographic abnormalities, clear changes in myocardial performance at rest were observed. The most obvious effect of thyroid hormone deficiency on the heart was a lengthening of both systolic and early diastolic time characteristics. Diastolic rather than systolic cardiac function was influenced by hypothyroidism.

Adult↗

Optimization of ventricular function by improving the activation sequence during ventricular pacing.

Abnormal electrical activation occurring during ventricular pacing reduces left ventricular (LV) pump function. Two strategies were compared to optimize LV function using ventricular pacing, minimal asynchrony and optimal sequence of electrical activation. ECG and hemodynamics aortic flowprobe, thermodilution cardiac output, LV pressure and its maximal rates of rise (LVdP/dtpos) and fall (LVdP/dtneg) were measured in anesthetized open-chest dogs (n = 7) with healthy hearts. The QRS duration (a measure of asynchrony of activation) was 47 +/- 5 ms during sinus rhythm and increased to 110 +/- 12 ms during DDD pacing at the right ventricular (RV) apex with a short AV interval. During pacing at the LV apex and LV base, the QRS duration was 8% +/- 7% and 15% +/- 7% (P < 0.05) longer than during RV apex pacing, respectively. Stroke volumes, LVdP/dtpos and LVdP/dtneg, however, were higher during LV apex (15% +/- 16%, 10% +/- 12% [P < 0.05], and 15% +/- 10%, respectively) and LV base pacing (11% +/- 12% [P < 0.05], 3% +/- 12%, and 3% +/- 11%, respectively) than during RV apex pacing. Systolic LV pressure was not influenced significantly by the site of pacing. Biventricular pacing (RV apex together with one or two LV sites) decreased the QRS duration by approximately 20% as compared with RV apex pacing, however, it did not improve stroke volumes, LVdP/dtpos and LVdP/dtneg beyond those during pacing at the LV apex alone. In conclusion, the sequence of electrical activation is a stronger determinant of ventricular function than the synchrony of activation. For optimal LV function the selection of an optimal single pacing site, like the LV apex, is more important than pacing from multiple sites.

Animals↗

Cellular pharmacology of phosphorothioate homooligodeoxynucleotides in human cells.

The uptake and distribution of phosphorothioate oligodeoxynucleotides by human cells were studied using 35S-labeled 28-mer phosphorothioate oligodeoxycytidine [S-(dC)28]. Accumulation of intracellular S-(dC)28 was found to be higher in the carcinoma cells (grown in monolayers) than in the leukemia cells (grown in suspension culture). A hepatoma cell line transfected with hepatitis B virus, 2215, was chosen for further studies. The uptake of S-(dC)28 was partially dependent on temperature and energy. The intracellular concentration was significantly higher than that in the medium and the amount accumulated was dependent on the extracellular concentration. It appears that the uptake of S-(dC)28 involves mechanisms of both fluid-phase pinocytosis and adsorptive endocytosis. Neither oligonucleotides nor 5'-phosphorylated nucleotides inhibited S-(dC)28 uptake. Unlike horseradish peroxidase, which was primarily associated with endosomes once it was taken into the cell, S-(dC)28 was found to be present in both nuclear and cytoplasmic fractions. Efflux of S-(dC)28 from the cell was multiphasic; a trapping mechanism that could be due to a potent interaction of S-(dC)28 with cellular proteins was implicated. This trapping mechanism could be responsible for the lack of biological activity such as cytotoxicity and antisense activity of phosphorothioate oligodeoxynucleotides in some human cells.

Carcinoma↗

Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: implications for antisense technology.

Phosphorothioate oligodeoxycytidine (S-dCn) was used as a model compound to examine the impact of the number of phosphorothioate linkages and their position on the inhibition of human DNA polymerases and RNase H in vitro. S-dCn with a chain length longer than 15 could inhibit human DNA polymerases and RNase H activities, in a linkage number-dependent manner. Longer oligomers were more potent inhibitors than shorter ones. Kinetic studies indicated that S-dC28 was a competitive inhibitor of DNA polymerase alpha and beta with respect to the DNA template, whereas it was a noncompetitive inhibitor of polymerases gamma and delta. S-dC28 was also a competitive inhibitor of RNase H1 and H2 with respect to RNA-DNA duplex. Susceptibility of these enzymes to inhibition by S-dC28 was in the order of delta approximately gamma greater than alpha greater than beta and RNase H1 greater than RNase H2. Structural-activity relationships were explored with a group of S-dC28 analogs that have phosphorothioate internucleotide linkages at various positions. The inhibitory effect depended on the total number of thioate linkages, rather than the position of the linkages within the oligomer or the chain length itself. No sequence specificity was found. In the presence of the complementary RNA, antisense phosphorothioates (S-oligos) exerted a biphasic effect on RNase H activity. At low concentrations S-oligos could enhance the cleavage of the RNA portion of S-oligo-RNA duplex, whereas at high concentrations (in excess of the complementary RNA) S-oligos could inhibit RNase H and protect the complementary RNA from degradation. Together, these results suggest that the non-sequence-specific inhibitory effect of S-oligos should be taken into consideration in designing antisense inhibitors. This inhibitory activity could be avoided by decreasing the number of phosphorothioate linkages at the backbone, and S-oligos of 15-20 residues are preferable in antisense molecule design.

Base Sequence↗