Biomedical subjects

M Pan

Publications and source records attributed to M Pan.

105 records · Page 6Linked to original sources

PubMed1986

Percutaneous transluminal balloon dilatation for discrete subaortic stenosis.

Seven patients, mean age 8 +/- 3.6 years, with clinical and hemodynamic diagnoses of discrete subaortic stenosis were treated by percutaneous transluminal balloon dilatation (PTBD) of the membrane during cardiac catheterization. One patient had an associated aortic coarctation that was first dilated. After PTBD left ventricular (LV) systolic pressure decreased significantly, from 181 +/- 25 to 139 +/- 11 mm Hg (p less than 0.005); peak gradient diminished from 65 +/- 18 to 12 +/- 9 mm Hg (p less than 0.001). Mild aortic regurgitation was present in 6 patients during basal conditions. After PTBD, the same degree of regurgitation was observed in all but 1 patient, in whom it disappeared. There were no major complications. Clinical observations after PTBD were consistent with hemodynamic findings. Precordial thrill always disappeared and the peak murmur became earlier in systole. In 2 patients the discrete subaortic stenosis was clearly visualized at 2-dimensional echocardiography as a fixed subvalvular structure throughout the cardiac cycle. After dilatation this was only identifiable at its implantation base; during contraction there was no fixed structure at the LV outflow tract. Four patients were hemodynamically reevaluated 6.7 +/- 1.7 months later and were found to have LV pressure relief and a degree of aortic regurgitation similar to those observed immediately after PTBD.

Angioplasty, Balloon↗

PubMed1985

Percutaneous transluminal angioplasty of stenotic ductus arteriosus.

This article describes our in vitro experience of balloon angioplasty of the ductus arteriosus (DA) in three post mortem human specimens, as well as an in vivo dilatation of a stenotic DA. The in vitro histologic observations revealed disruption of the intima and areas of pathologically fragmented and disorganized fibers at the media, with integrity of the ductal wall in all three DA. These findings led us to attempt percutaneous transluminal angioplasty (PTA) of a stenotic DA in a 2.3-kg newborn infant with hypoplastic left heart syndrome in a very deteriorated clinical condition. A Rashkind septostomy was associated with PTA of the stenotic DA. Following this, the gradients across the DA and across the atrial septum disappeared and the ductal angiographic diameter increased. Although an improved clinical condition was observed during the following hours, he died 1 day after. At necropsy, we found integrity of the ductal wall with histological changes similar to that observed in vitro. We conclude that PTA of stenotic DA could represent an alternative for palliative treatment of DA-dependent congenital heart disease.

Angioplasty, Balloon↗

PubMed1984

Stimulation of Na+,K+-ATPase of isolated smooth muscle membranes by the Ca2+ channel inhibitors, nimodipine and nitrendipine.

Nimodipine (0.015 to 1.5 microM) increased Na+, K+-ATPase activity by 70-120% in isolated smooth muscle membranes. At 0.015 microM, nitrendipine, but not nifedipine, verapamil or diltiazem, also activated this enzyme. Nimodipine stimulated this Na+, K+ATPase three times more than nitrendipine at 15 nM. Marked stimulation of Na+,K+-ATPase by nimodipine was seen in membranes from rat and guinea pig aorta and rat vas deferens, but not in membranes from guinea pig heart or brain. Although it is not known whether these results are applicable to intact cells, the results are consistent with the hypothesis that vasodilation produced by nimodipine and nitrendipine may be due not only to inhibition of Ca2+ entry but also to the stimulation of the Na+ pump.

Animals↗

PubMed1983

Radioreceptor and high-performance liquid chromatographic assays for the calcium channel antagonist nitrendipine in serum.

Radioreceptor and high-performance liquid chromatographic (HPLC) assays for nitrendipine were developed and applied to the analysis of serum samples. The HPLC assay required both extraction and concentration of the serum samples, whereas the radioreceptor assay involved only direct dilution of the serum. The HPLC assay, in contrast to the radioreceptor assay, can be used for detection and quantitative analysis of biologically inactive metabolites. The radioreceptor assay is based on the competition between nitrendipine in serum and [3H]nitrendipine for high-affinity binding sites on cardiac membranes. Forty-two serum samples were obtained from five volunteers, and the HPLC and radioreceptor assay results were compared. A correlation coefficient of 0.98 was found between the results of the two assays within the nitrendipine serum concentration range of 1 to 20 ng/ml. No significant levels of active metabolites or any other interferences were found. The radioreceptor assay provides a specific and sensitive alternative to HPLC; it is rapid and inexpensive and with minor modifications may be applicable to most presently available Ca2+ channel antagonists.

Animals↗

PubMed1979

Psoralen-DNA cross-linking photoadducts in dyskeratosis congenita: delay in excision and promotion of sister chromatid exchange.

Dyskeratosis congenita is a rare X-linked recessive disease, characterized by mucosal leukokeratosis, nail dystrophy, telangiectasia, reticulated hyperpigmentation, pancytopenia, and a heightened susceptibility to infection and malignancy. We exposed cultured fibroblasts and peripheral leukocytes from normal persons and from 2 unrelated young adult men with dyskeratosis congenita to 4,5',8-trimethylpsoralen and ultraviolet light. We than compared certain of their responses. Labeled DNA from fibroblasts exposed to 4,5',8-trimethylpsoralen and ultraviolet light showed fast-sedimenting DNA, a pattern we interpreted as evidence that cross-linking, psoralen-DNA photoadducts had been formed by the treatment. Fast-sedimenting DNA persisted for 24 hr in dyskeratosis congenita cells but disappeared from normal cells during a 24-hr repair period. Cultured peripheral blood leukocytes from persons with this syndrome similarly exposed to 4,5',8-trimethylpsoralen and ultraviolet light developed more sister chromatid exchanges than did cells from normal persons. These data suggest that a heightened susceptibility in DNA cross-links may be of fundamental importance in the etiology of dyskeratosis congenita.

Adolescent↗

PubMedDate not supplied

Percutaneous interventions on severe coarctation of the aorta: a 21-year experience.

Different percutaneous interventions can be used to treat coarctation of the aorta. However, a great amount of information is still needed regarding the long-term course. This article reviews our experience spanning 21 years in the percutaneous treatment of aortic coarctation. Four different conditions for treatment were considered. The first condition 1 (group 1) was balloon angioplasty in neonates and infants with untractable heart failure (n = 54; mean age, 1.2 +/- 1.4 months). After balloon angioplasty, most infants sustained significant clinical improvement. However, 9 patients died in the hospital (17%). As a result, we monitored the course of the 45 survivors during a mean period of 10 +/- 6 years (range, 1-19). During this follow-up period, 17 patients needed a single additional intervention on coarctation (8 underwent surgery and 9 were treated percutaneously). After this second treatment, 11 patients needed one or more further interventions. The actuarial survival probability was 83% at 19 years, with 43% of patients remaining surgery free and 23% reintervention free. The second condition (group 2) was balloon angioplasty in children and adults with coarctation of the aorta before the stenting era (n = 28; mean age, 13 +/- 8 years). After treatment, serial hemodynamic and angiographic studies were performed. The long-term relief was higher in patients with a discrete type of coarctation. The rate of late aneurysm formation was 6%. The third condition (group 3) was stent palliation in infants and children younger than the age of 6 years (n = 17; mean age, 2.1 +/- 1.7 years). The stent was implanted for nondilatable stenoses, as a nondefinitive procedure. Stent palliation provides complete initial relief in hypoplastic coarctations or life-threatening conditions. However, further stent expansion is required to ensure adequate stent diameter in the growing aortic wall. In addition, late intrastent proliferation may occur in small stent diameters (18%) and aneurysm formation in hypoplastic coarctations (18%). Both late complications can be managed percutaneously. The fourth condition (group 4) was stent repair of severe aortic coarctation in adults, adolescents, and children older than the age of 6 years (n = 73; mean age, 20 +/- 12 years). Significant relief was observed after treatment, which persisted at follow-up. One patient died at treatment (1.3%). After a mean follow-up of 5 +/- 3 years, all 72 patients remained symptom free and no restenosis or late aneurysm were detected.

Adolescent↗

PubMedDate not supplied

Inhibition of pulmonary microvascular endothelial glutamine transport by glucocorticoids and endotoxin.

BACKGROUND: During septic states, the lungs produce increased amounts of glutamine, an event that is mediated by both endotoxin and glucocorticoid hormones and is presumed to be due to accelerated intracellular glutamine biosynthesis. Because enhanced net glutamine release in vivo could also be due to a decrease in cellular uptake, we assayed glutamine transport in cultured rat microvascular pulmonary endothelial cells. METHODS: The effect of Escherichia coli endotoxin (LPS, 1 microgram/mL), various cytokines, and dexamethasone (DEX, 0.1 mumol/L) on glutamine transport activity was studied in rat lung microvascular endothelial cells grown in varying glutamine concentrations (0, 0.1, 0.5, and 2 mmol/L). Experiments were also performed in cells treated with cycloheximide, actinomycin D, or chelerythrine chloride. RESULTS: More than 90% of glutamine transport was mediated by the Na+ -dependent transport system ASC. DEX and LPS inhibited endothelial glutamine uptake in a time- and dose-dependent manner, a response that was only observed with incubation medium contained the lower concentrations of glutamine. Neither DEX nor LPS altered transport activity in cells cultured in medium containing 2 mmol glutamine/L. There was no synergistic or additive effect when both compounds were added together. The cytokines tumor necrosis factor alpha, interleukin (IL) 1, IL-2, and IL-6 did not alter glutamine transport. both DEX and LPS inhibited glutamine transport by decreasing transporter maximal transport velocity (Vmax) without affecting transporter affinity (Km). Cycloheximide and actinomycin D abrogated the inhibition of transport activity that was observed in DEX- or LPS-treated cells, whereas the protein kinase C inhibitor chelerythrine chloride had no effect on either control or stimulated glutamine transport. CONCLUSIONS: These data suggest that DEX and LPS "down-regulate" glutamine uptake by lung microvascular endothelial cells by inducing the synthesis of an inhibitory protein that modulates the activity of the system ASC protein. This response in vitro appears to be influenced by the extracellular glutamine concentration. This decrease in microvascular endothelial glutamine transport may be one mechanism by which net lung glutamine release is enhanced during critical illness.

Animals↗

PubMedDate not supplied

Lipopolysaccharide and tumor necrosis factor stimulate lung microvascular arginine uptake, a response attenuated by dexamethasone.

BACKGROUND: Lipopolysaccharide (LPS), tumor necrosis factor-alpha, (TNF), and glucocorticoids can modulate endothelial nitric oxide (NO) production. L-Arginine is the exclusive precursor for NO biosynthesis, suggesting that NO generation and arginine transport are intimately linked. METHODS: To further study this relationship, we examined the effects of LPS, TNF, and dexamethasone (DEX) on arginine uptake by rat lung microvascular endothelial cells. The transport of radiolabeled arginine was assayed in confluent cells grown in 24-well plates. RESULTS: The bulk (> 90%) of arginine transport was mediated by the Na(+)-independent carriers System y+ and System b0,+. Arginine transport was stimulated independently by LPS and TNF, a response first observed at 10 hours. Together, both agents exerted an additive effect on carrier-mediated uptake. The LPS- and TNF-induced increase in arginine transport activity was blocked by cycloheximide and actinomycin D, indicating the requirement for RNA and protein synthesis. The enhancement in transport activity was primarily due to an increase in Systems y+ maximal transport capacity (Vmax) with no change in transporter affinity and little change in System b0,+ activity. Treatment of cells with dexamethasone inhibited arginine transport activity in a time- and dose-dependent manner, an event that was abrogated by both actinomycin D and cycloheximide. The combination of DEX and LPS and TNF abrogated each other's antagonistic effects. CONCLUSIONS: These data indicate that LPS and TNF additively stimulate arginine transport in lung microvascular endothelial cells via a pathway that requires de novo protein synthesis (possibly of the transporter protein itself) and that this response is attenuated by DEX.

Animals↗

PubMedDate not supplied