Search PubMed⌕ Search

Biomedical subjects

S K Morcos

Publications and source records attributed to S K Morcos.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effect of radiographic contrast media on histamine release from human mast cells and basophils.

Radiographic contrast media (RCM) cause histamine-dependent allergic-like reactions. The direct effects of diatrizoate (high osmolar ionic monomer), ioxaglate (low osmolar ionic dimer), iopromide (low osmolar non ionic monomer) and iotrolan (iso-osmolar non ionic dimer) at the concentration of 200 mgI ml-1 (60 min exposure) on the release of histamine from human basophils, human lung mast cells (HLMC), and human skin mast cells (HSMC) were investigated. Diatrizoate induced 48 +/- 4% histamine release in basophils, 15 +/- 3% in HLMC and 25 +/- 6% in HSMC. The remaining RCM were relatively ineffective activators of histamine release in both HLMC and HSMC (ioxaglate 4 +/- 1% and 4 +/- 1%, iopromide 5 +/- 1% and 7 +/- 2%, iotrolan 7 +/- 2% and 10 +/- 3%, respectively). Both iotrolan and ioxaglate were effective in basophils inducing 21 +/- 3% and 24 +/- 6% histamine release, respectively, whereas iopromide was relatively ineffective (7 +/- 4%). Diatrizoate induced histamine release from all three cell types with optimal levels of histamine release after a 2-4 h incubation although significant levels occurred within 15 min. Dose-dependent histamine release from HLMC occurred in all four types of RCM, the largest response (37 +/- 3%) being produced by diatrizoate. The effect of osmolality on histamine release was investigated using different concentrations of mannitol solutions (0.25, 0.5 and 1 M). Histamine release from HLMC, HSMC and basophils after 90 min exposure to mannitol (1 M) was 24 +/- 2% (p < 0.05), 9 +/- 3% (p = 0.06) and 49 +/- 1% (p < 0.05), respectively, suggesting that hyperosmolality per se can induce histamine release from basophils and mast cells. Diatrizoate-induced histamine release in all three cell types was significantly reduced by lowering the temperature to 0 degree C and partially attenuated by the metabolic inhibitors antimycin A (1 microM) and 2-deoxyglucose (5 mM), and by the omission of glucose from the buffer solution. Diatrizoate-induced histamine release was not dependent on extracellular calcium. These data suggest that diatrizoate induces histamine release at least in part by non-cytotoxic mechanisms.

Basophils↗
PubMed1998

Contrast media-induced nephrotoxicity--questions and answers.

The intravascular administration of contrast media (CM) can produce acute haemodynamic changes in the kidney characterized by an increase in renal vascular resistance and a decrease in the glomerular filtration rate (GFR). These changes may lead to clinically significant reduction in renal function in patients with pre-existing risk factors such as diabetic nephropathy, congestive heart failure and dehydration. The pathophysiology of the renal haemodynamic effects of CM involves activation of the tubuloglomerular feedback (TGF) mechanism and the modulation of the intrarenal production of vasoactive mediators such as prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is osmolality-dependent and accounts for about 50% of the acute functional effects of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM. Endothelin and adenosine play a crucial role in mediating the acute functional effects of CM. Antagonists of these mediators attenuate the reduction in renal function induced by contrast agents. Vacuolization of the cells of the proximal tubules and necrosis of those of the medullary ascending limbs of loops of Henle are the main structural effects of CM in the kidney. The reduction in renal function induced by CM could be minimized by the use of low osmolar CM and adequate hydration. The prophylactic administration of calcium channel blockers and adenosine antagonists such as theophylline may also offer some protective effect.

Animals↗
PubMed1998

The effect of radiographic contrast media on human vascular smooth muscle cells.

The relation between intravascular radiographic contrast media (RCM) and myointimal hyperplasia after percutaneous transluminal angioplasty is not known. We have investigated the cytotoxic effects of RCM on human vascular smooth muscle cells (VSMCs) and their effect on the growth of these cells. The cytotoxic effects of RCM were studied using human VSMCs. The cells after being grown to confluency were exposed for 60 min to 250 mgI ml-1 of diatrizoate, ioxaglate, iopromide, iotrolan and saturated mannitol solutions. The control group was treated with only 15% fetal calf serum (FCS) containing medium. The viability of the cells was examined using the trypan blue exclusion test. The effect of RCM on growth was assessed by exposing the VSMCs after growth arrest, for either 15 or 60 min to 250 mgI ml-1 of diatrozoate, ioxaglate, iopromide, iotrolan and saturated mannitol solution. There was no significant change in the viability of the VSMCs after 60 min exposure to iopromide, iotrolan, saturated mannitol solution, and after 15 min exposure to diatrizoate or ioxaglate. After exposure to diatrizoate or ioxaglate for 60 min, 16.5 +/- 2.2% or 9.2 +/- 2.6% dead cells were found, respectively (p < 0.05 versus control). In the growth assay of VSMCs, diatrizoate, ioxaglate and saturated mannitol solutions reduced the growth rate (p < 0.05 versus control). No significant change was observed with iopromide and iotrolan. In conclusion, ionic RCM have cytotoxic and cytostatic effects on VSMCs while non-ionic media have no effects. There is no direct stimulatory effect of contrast media on the growth of VSMCs. The cytotoxic and cytostatic effects of contrast media seems to be both osmolality and chemotoxicity dependent. Low osmolar non-ionic RCM are not likely to contribute to the mechanisms responsible for myointimal hyperplasia after angioplasty.

Cell Death↗
PubMed1998

Ventilatory effects of radiographic contrast media.

Respiratory adverse reactions have been reported with the use of contrast media. This study investigates the effects of different radiographic contrast media (RCM) on ventilation and blood gases. Tidal volume and respiratory rate of male Wistar rats anaesthetised with Inactin (100 mg kg-1 intraperitoneally), were measured continuously by integration of tracheal airflow. Contrast media (diatrizoate 370, ioxaglate 320 and iopromide 300) or mannitol controls matched for volume, pH and osmolarity (4 ml kg-1) were administered via a jugular cannula (n > or = 6 per group). Carotid artery blood was sampled at 2, 7, 12, 17, 25 and 30 min post-injection for PaO2, PaCO2 and pH. Systemic blood pressure was monitored from the same cannula. No significant reduction was observed in minute ventilation (tidal volume x respiratory rate per minute) with any of the contrast media. All contrast media and control solutions produced a fall in PaO2 within 4 min; returning to basal levels at 10 min (diatrizoate 35.6% (p < 0.05), ioxaglate 15.2% (p < 0.02), iopromide 16.2% (p < 0.01); controls: 17.3% (p < 0.01), 13.5% (p < 0.02) and 12.0% (NS), respectively). The fall in PaO2 induced by diatrizoate was significantly (p < 0.05) larger in comparison to the other groups. Ioxaglate, iopromide and their mannitol controls induced a comparable fall in PaO2. There was a concurrent rise in PaCO2 and fall in pH that reached significance for diatrizoate (p < 0.01). The changes in blood gases with RCM administration cannot be explained by changes in ventilation and may be due to an effect on pulmonary perfusion.

Animals↗
PubMed1997

Effect of radiographic contrast media on endothelium derived nitric oxide-dependent renal vasodilatation.

The effect of diatrizoate (Urografin325) on the cumulative dose-response curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mumol l-1) on the cumulative concentration-response curve of the vasodilatory response to acetylcholine and sodium nitroprusside was also studied. Acetylcholine is a vasodilator dependent on nitric oxide (NO) synthesis by the endothelium; sodium nitroprusside is a vasodilator not dependent on endogenous NO synthesis and L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-NAME (10 mumol l-1) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123, 10 mumol l-1) was also studied. In all experiments an infusion of angiotensin II (5 ng min-1) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0 +/- 1.7%, (p < 0.05). Diatrizoate (20 mgl ml-1 perfusate concentration) which induced a sustained fall in the RPF (-31.0 +/- 1.7%, p < 0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8 +/- 2.2%, p < 0.05) was observed. In contrast, L-NAME (10 mumol l-1) completely abolished the vasodilatory effect of acetylcholine and produced instead a modest decrease in RPF by -5.0 +/- 1.7% (p < 0.05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sodium nitroprusside was 23.1 +/- 2.0% (p < 0.05) in the absence of L-NAME and 21.2 +/- 2.2% (p < 0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3 +/- 1.4 ml min-1 g-1 to 26.5 +/- 1.0 ml min-1 g-1 (p < 0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4 +/- 3.0 ml min-1 g-1 to 27.2 +/- 2.7 ml min-1 g-1 (p < 0.05). There was no difference between the two groups (p > 0.05). In conclusion, diatrizoate did not interfere with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by contrast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The renal vasodilatation induced by diatrizoate is not dependent on endogenous production of NO.

Acetylcholine↗
PubMed1997

Clinicians' interpretation of the indeterminate ventilation-perfusion scan report.

Most patients with suspected pulmonary embolism are initially investigated by radio-nuclide ventilation-perfusion (VQ) scanning. Approximately 70% of VQ scans are "indeterminate". Further investigations should be considered in such patients in order to establish a definitive diagnosis. However, these investigations are rarely requested in patients with indeterminate scans in our institution. We therefore decided to review the casenotes of such patients to determine their subsequent management. Over a 9 month period, 131 (32%) out of a total of 413 consecutive VQ scans were reported as indeterminate. The casenotes of 111 of these patients (65 female, 46 male, mean age 65 years, range 17-91 years) were reviewed. 52 of the 111 patients (46%) were treated on clinical grounds without further investigation; 12 patients (11%) had further investigation; and in 39 of the cases (35%) the VQ scan report was misinterpreted. 20 (38%) of the 52 patients managed on clinical grounds were treated for pulmonary embolus with anticoagulation and 26 (50%) were not anticoagulated. Of the 12 patients who were investigated further, nine had lower limb Doppler ultrasound and three had contrast venography. No patients had pulmonary angiography. Of the 39 cases where the VQ report was misinterpreted, the result was misquoted in the casenotes of 37 (95%) as negative for PE and none of these patients were anticoagulated, and in two cases (5%) it was misquoted as positive for PE and anticoagulant therapy was instituted. The misunderstanding was observed in all clinical firms. Such misinterpretation may have significant implications, since 30-40% of patients with indeterminate scans may have had PE. Our findings suggest that clinicians need to be better informed of the significance of an indeterminate VQ scan result.

Adolescent↗
PubMed1997

Effects of radiographic contrast media on the tension of isolated small pulmonary arteries.

The aim of the study was to establish the direct effects of radiographic contrast media (RCM) on the tension of isolated small pulmonary arteries and to investigate any mediation by nitric oxide (NO) and endothelin (ET). Small pulmonary arteries (0.3-0.6 mm in diameter) from male Wistar rats were mounted in a Cambustion vessel myograph and vessel wall tension recorded. The effects of 10, 20, 40, 80, 150, 200 and 250 mgl mI-1 of diatrizoate, ioxaglate, iopromide and iotrolan and their mannitol osmolar control from basal condition, and when the vessels were preconstricted with prostaglandin F2 alpha (PGF2 alpha) either submaximally (10 microM) or maximally (100 microM), were studied. The constrictor response to diatrizoate (40 mgI ml-1) was tested in the presence of non-selective endothelin receptor antagonist (10 microM SB209670). The dilator response to ioxaglate (80 mgI ml-1) was tested in the presence of L-nitroarginine methyl ester (L-NAME, 100 microM). All RCM caused biphasic changes in tension, a small transient fall (dilatation) followed by a sustained rise (constriction). Mannitol caused constriction only. The potency order of constrictions at 10-40 mgI ml-1 was diatrizoate > iopromide > ioxaglate > iotrolan. When the vessels were preconstricted with PGF2 alpha, RCM caused predominantly dilatation; ioxaglate produced the largest effect (-42.1 +/- 3.1%, n = 12). Mannitol caused constriction only. SB209607 had no effect on the constrictor effect of diatrizoate [41.9 +/- 2.3 alone, 42.1 +/- 2.7 with SB209670, n = 10]. L-NAME had no effect on the dilator response to ioxaglate [-38.2 +/- 1.6 alone, -43.6 +/- 2.2 with L-NAME, n = 8]. It is tempting to postulate that dimeric RCM may cause the least changes in the pulmonary circulation during angiography.

Animals↗
PubMed1995

The acute effect of ioversol on kidney function: role of endothelin.

The effect of ioversol, a non-ionic monomer with high hydrophilicity, on renal function was studied using the isolated perfused rat kidney (IPRK). The involvement of endothelin in the renal effect of ioversol was established pharmacologically using the selective endothelin ETA receptor antagonist BQ123. Ioversol 20 mgI/ml produced a sustained fall in both renal perfusate flow (RPF) and the glomerular filtration rate (GFR) together with a fall in sodium reabsorption (FRNa) and increase in urine flow (n = 6). In the presence of BQ123 (10 microM), the effect of ioversol 20 mgI/ml on GFR was completely abolished and the fall in RPF and FRNa markedly reduced (n = 6). These results suggest that effect of ioversol on renal haemodynamics in the IPRK is mediated by endothelin. Ioversol produced a significantly smaller decrease in GFR than iopromide, a contrast media with similar osmolality but lower hydrophilicity, when compared to a previous study using an identical experimental technique. Increased hydrophilicity may therefore present an advantage for ioversol, reducing its effects on renal function.

Animals↗
PubMed1995

Bosentan, an orally active endothelin antagonist: effect on the renal response to contrast media.

PURPOSE: To examine the effect of bosentan, an orally active endothelin-receptor antagonist, on the renal response to contrast media in the isolated perfused rat kidney (IPRK) and to establish whether bosentan can inhibit contrast media-induced nephrotoxicity in a multiple-insult model in the conscious rat. MATERIALS AND METHODS: Renal function was measured in the IPRK (n = 24) and in the rats that had undergone unilateral nephrectomy, were maintained on a salt-free diet, and were receiving indomethacin (10 mg/kg/d; n = 60). RESULTS: In the IPRK, diatrizoate and iotrolan reduced the glomerular filtration rate and renal perfusate flow, an effect markedly inhibited by bosentan (n = 6 per group). In the multiple-insult rat model, the fall in creatinine clearance produced by diatrizoate was also markedly inhibited by bosentan (n = 15 per group). CONCLUSION: Endothelin antagonists such as bosentan may be used to reduce the prevalence of contrast-induced nephrotoxicity.

Administration, Oral↗
PubMed1995

Does peppermint oil relieve spasm during barium enema?

The effectiveness of topical peppermint oil added to barium sulphate suspension in relieving colonic muscle spasm during double contrast barium enema examination was assessed in a double blind study. 141 patients were randomized either to a control group (71 patients) examined with standard barium suspension or to the treatment group which received peppermint oil mixed with the barium preparation. No residual spasm was evident in a significant proportion of patients in the treated group (60%) compared with the control group (35%) (p < 0.001). The patients' acceptability of the procedure was good and there were no adverse effects on the overall quality of the examination. In conclusion, the addition of peppermint oil to the barium suspension seems to reduce the incidence of colonic spasm during the examination. The technique is simple, safe, cheap and it may lessen the need for intravenous administration of spasmolytic agents.

Adult↗