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Biomedical subjects

R E Katholi

Publications and source records attributed to R E Katholi.

At least 19 recordsLinked to original sources

Clinical adaptation of a high-performance liquid chromatographic method for the assay of pyridoxal 5'-phosphate in human plasma.

Vitamin B6, measured as pyridoxal 5'-phosphate (PLP), is a co-enzyme in the transsulfuration pathway of homocysteine metabolism. Since depletion of PLP has been suggested as an independent risk factor for coronary artery disease, PLP is frequently measured to guide patient care. By a change and utilization of an Aquasil C18 column and the addition of an acetonitrile clean-up gradient to the potassium phosphate, with sodium perchlorate and bisulfite buffer between samples we report the modification of a previously described method for analysis of PLP. The result is a more practical, efficient, reliable and robust method for daily clinical use. We also determined and report that it is critical to protect freshly prepared standard PLP samples from light exposure during assay preparation.

Chromatography, High Pressure Liquid↗

Proximal tubule cell response to radiographic contrast media.

Renal dysfunction associated with contrast media (CM) administration is generally attributed to reduced renal blood flow. Studies, however, also suggest direct tubular effects of CM, whose mechanisms remain unclear. This study was conducted to assess the chemotoxic effects of iopamidol, a prototypic CM, on a porcine proximal tubule (PT) cell line, LLC-PK(1) cells. Results indicate that iopamidol did not affect cell viability (determined by trypan blue exclusion and fluorescein staining), but did reduce cell proliferation. Moreover, iopamidol altered mitochondrial function, as determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and mitochondrial membrane potential. Decreased MTT reduction was evident with all CM tested, and its rapid recovery after CM removal suggests that inhibition of mitochondrial function is reversible. Injury to PT cells by iopamidol is supported by the fact that CM increase extracellular adenosine, an indicator of cellular stress. This study provides greater insight into the mechanism underlying the nephrotoxicity induced by contrast in patients and explains the reversibility of this toxicity.

Animals↗

Clinical predictors of improved long-term blood pressure control after successful stenting of hypertensive patients with obstructive renal artery atherosclerosis.

Despite a high procedural success rate, long-term blood pressure control after successful renal artery stenting of hypertensive patients has been inconsistent. This most likely reflects the absence of clinical guidelines for the selection of patients likely to benefit from renal revascularization. A cohort of 150 consecutive hypertensive patients (mean age, 66.7 years; 86 women) with 180 renal artery lesions (> or =75%) underwent primary Palmaz stent deployment. Mean arterial blood pressure (MAP), serum creatinine, and antihypertensive medication requirements were monitored prospectively. Specific definitions of blood pressure cure, improvement, or treatment failure were followed. Renal artery duplex Doppler or angiography was performed to assess stent patency at a mean 13 months (range, 7-15 months). Multivariate logistic regression analysis was used to select clinical variables that best related to a beneficial blood pressure control at follow-up. The procedural success rate was 97.3% (146 patients) and major in-laboratory complications were infrequent (1.3%). Late MAP values in 127 patients (91%) fell from 110 +/- 13.7 to 97.6 +/- 10.6 mm Hg (P < 0.001); antihypertensive medication requirements decreased from 2.9 +/- 1.2 to 1.9 +/- 1.1 (P < 0.01). The 13-month stent restenosis rate defined by duplex Doppler or angiography was 12%. Multivariate logistic regression analysis identified a preprocedure MAP of >110 mm Hg (odds ratio, 2.9; P = 0.003) and bilateral renal stenoses (odds ratio, 4.6; P = 0.009) as predictors of a beneficial blood pressure response at follow-up. This study provides general preprocedure guidelines for the selection of hypertensive patients with atherosclerotic renal lesions likely to benefit from primary Palmaz stenting and confirms a high procedural success and low stent restenosis rate.

Aged↗

Oxygen free radicals and contrast nephropathy.

Ionic, high-osmolality contrast medium causes nephrotoxicity associated with increased intrarenal adenosine production. To test the hypothesis that oxygen free radicals (produced during intrarenal adenosine catabolism to xanthine) should be implicated in the pathogenesis of ionic, high-osmolality contrast medium nephrotoxicity in humans and to determine whether magnesium protects the kidney from oxygen free radical injury following contrast, 39 patients with mild renal dysfunction were divided into low (LoMg++) and normal (NlMg++) magnesium states and randomized to precoronary angiography oral allopurinol (a xanthine oxidase inhibitor) or placebo. Creatinine clearance and urinary xanthine excretion were measured before and after angiography. Forty-eight hours after contrast medium exposure, placebo-treated LoMg++ and NlMg++ patients had 61%+/-5% and 67%+/-6% increases in urinary xanthine excretion, respectively; however, placebo-treated LoMg++ patients had a greater (79%+/-9% v 35%+/-6%; P < 0.01) decrease in creatinine clearance than placebo-treated NlMg++ patients. Allopurinol-treated LoMg++ and NlMg++ patients had no significant change in urinary xanthine excretion, but did have 40%+/-7% and 33%+/-5% decreases, respectively, in creatinine clearance 48 hours after contrast medium exposure. There was no difference in renal dysfunctional response among placebo-treated NlMg++ patients or allopurinol-treated LoMg++ or NlMg++ patients. These data suggest (1) that oxygen free radicals contribute to ionic, high-osmolality contrast medium nephrotoxicity in hypomagnesemic patients with mild renal disease and (2) that magnesium attenuates the nephrotoxicity mediated by oxygen free radicals.

Adenosine↗

Nephrotoxicity from contrast media: attenuation with theophylline.

PURPOSE: To determine if depression of creatinine clearance after administration of contrast medium may be prevented with theophylline. MATERIALS AND METHODS: A nonionic, low-osmolality contrast medium (iopamidol) or an ionic, high-osmolality contrast medium (sodium diatrizoate) was administered to 93 patients. Before the examination, these patients were given theophylline or a placebo orally. There were also 30 patients who received an adenosine-uptake inhibitor (dipyridamole). Creatinine clearance and urinary adenosine levels were measured before and after angiography. RESULTS: Creatinine clearance decreased 18% +/- 4 in the placebo-iopamidol group but did not decrease in the theophylline group; urinary adenosine increased 67% +/- 7. Creatinine clearance decreased 42% +/- 5 in the placebo-sodium diatrizoate group and decreased 24% +/- 3 in the theophylline group; urinary adenosine increased 119% +/- 8. In the dipyridamole group in which iopamidol was given, urinary adenosine increased 96% +/- 7 and creatinine clearance decreased 37% +/- 5. CONCLUSION: Intrarenal adenosine can be implicated in the pathogenesis of hypertonic contrast medium nephrotoxicity.

Adenosine↗

A difference between front-loaded streptokinase and standard-dose recombinant tissue-type plasminogen activator in preserving left ventricular function after acute myocardial infarction (the Central Illinois Thrombolytic Therapy Study).

A blinded, randomized trial compared the effects of front-loaded streptokinase with those of the conventional dose of intravenous recombinant tissue-type plasminogen activator (rt-PA) on left ventricular (LV) function after acute myocardial infarction (AMI). Thrombolytic therapy was administered in the emergency departments of 30 community hospitals in central Illinois, and subsequent studies were performed at 1 tertiary referral center. Patients aged < or = 75 years with a first AMI who could be treated within 4 hours of the onset of chest pain were randomly assigned to receive either streptokinase (375,000 IU bolus, followed by 1,125,000 IU over 1 hour) or rt-PA (10 mg bolus, followed by 50 mg in the first hour, and 20 mg/hour for the next 2 hours). All patients were treated with aspirin (325 mg) and intravenous heparin. Patients were transferred for angiography within 24 hours. During the 30-month study, 253 patients were treated with intravenous thrombolytic therapy 2.4 +/- 1.0 hour after the onset of AMI. In patients with anterior wall AMI (n = 90), global LV ejection fraction measured by angiography within 24 hours was 45 +/- 12% with rt-PA, and 39 +/- 13% with streptokinase (p < 0.03). Convalescent radionuclide angiography documented a persistent beneficial effect of rt-PA on LV regional wall contractility, but not global ejection fraction. There were no differences between rt-PA and streptokinase in preserving global or regional LV function in patients with inferior wall AMI.

Aged↗

Nephrotoxicity of nonionic low-osmolality versus ionic high-osmolality contrast media: a prospective double-blind randomized comparison in human beings.

To test whether a nonionic, low-osmolality contrast medium (iopamidol) administered for coronary angiography was less harmful to renal function than ionic, high-osmolality medium (sodium diatrizoate), a prospective, double-blind randomized study of 70 patients with normal or mildly depressed renal function (serum creatinine < or = 2.0 mg/dL (175 mumol/L) was performed. Creatinine clearance was determined before coronary angiography and 24 and 48 hours after. There were no significant differences between the low- and high-osmolality groups with regard to age, baseline creatinine clearance, or dose of contrast medium given. In patients receiving low-osmolality medium (n = 35), creatinine clearance decreased by 19% +/- 13 (1 standard deviation) at 24 hours and recovered by 48 hours. In patients receiving high-osmolality medium (n = 35), creatinine clearance decreased by 40% +/- 16 at 24 hours and remained depressed by 47% +/- 14 at 48 hours. In patients with normal or mildly depressed renal function, use of a non-ionic, low-osmolality contrast medium minimized nephrotoxicity as measured by reductions in creatinine clearance after coronary angiography.

Adolescent↗

Increased incidence of silent ischemia after acute myocardial infarction.

OBJECTIVE: To determine the incidence of angina pectoris during induced myocardial ischemia in patients who have had thrombolytic therapy for acute myocardial infarction in comparison with patients with angina pectoris. DESIGN: During percutaneous transluminal coronary angioplasty, both study groups had coronary artery occlusion by the balloon dilatation catheter for 5 minutes. SETTING: A tertiary, cardiology referral center. PATIENTS: Twenty-five patients with angina pectoris who were undergoing angioplasty were compared with 30 patients having angioplasty 2 days after thrombolytic therapy for acute myocardial infarction. OUTCOMES: Development of angina pectoris during balloon occlusion of the coronary artery was the primary end point; the ischemic response and muscle viability were assessed using both surface and intracoronary electrocardiograms and pulmonary artery wedge pressure. RESULTS: During balloon occlusion 16 (64%) of 25 patients in the angina pectoris group developed angina. In contrast, nine (30%) of 30 patients in the thrombolysis group had angina pectoris during balloon occlusion of the infarct artery (P less than .01). The electrocardiographic response to ischemia and changes in pulmonary wedge pressure were similar in the two study groups. CONCLUSION: After thrombolytic therapy for myocardial infarction, silent ischemia may be the rule rather than the exception.

Angina Pectoris↗

Six-year survival after coronary thrombolysis and early revascularization for acute myocardial infarction.

Six-year follow-up was conducted in a consecutive series of 192 patients receiving thrombolytic therapy for acute myocardial infarction (AMI) with ST-segment elevation. Cardiac catheterization was performed within a day, and patients with an open infarct artery routinely had early revascularization: 99 (67%) underwent coronary bypass surgery and 18 (12%) coronary angioplasty. With this treatment strategy, 6-year cardiac mortality was 14.5%, 6% (12 patients) in hospital and 9% (16 patients) for survivors of hospitalization. Multivariate analysis showed that predictors of cardiac death among survivors of hospitalization were a closed infarct artery at catheterization (p less than 0.01), diabetes (p less than 0.01) and anterior myocardial infarction (p = 0.01). A subset of 146 patients underwent radionuclide angiography before hospital discharge; for them, predictors of mortality were a closed infarct artery at catheterization (p less than 0.01), anterior wall AMI (p = 0.02), and Killip class III to IV on admission (p less than 0.06). Left ventricular ejection fraction was not a significant predictor of mortality for this subset of patients.

Aged↗

Axial heterogeneity of adenosine transport and metabolism in the rabbit proximal tubule.

Transport and metabolism of adenosine were studied in the S1, S2, and S3 segments of the rabbit proximal renal tubule. Isolated segments were perfused in vitro with uniformly labelled 14C-adenosine to measure the lumen-to-bath flux of adenosine. This flux rate was measured by the disappearance of 14C from the luminal fluid (JD) and simultaneously by the appearance of 14C in the bathing solution (JA), expressed as femtomoles per minute per millimeter of tubule length (fmol.min-1.mm-1). At a perfused concentration of 83.3 microM adenosine, when corrected for metabolism, the JDs for adenosine in the S1, S2, and S3 segments were 735, 212, and 273, respectively. JAs, corrected for metabolism, were 0, 0, and 4.8 fmol.min-1.mm-1 for the S1, S2, and S3 segments, indicating that very little or no 14C-adenosine moved across the basolateral membrane. To correct for metabolism of 14C-adenosine, the perfusion fluid, collected fluid, tubular extract, and bathing fluid, from three tubules of each segment type, were analyzed by high-performance liquid chromatography to identify 14C-adenosine and its 14C-metabolites. At 83.3 microM, all segments metabolized adenosine extensively. Consequently, adenosine-5'-monophosphate (AMP) and inosine were found in tubule cells of all segments. Inosine also appeared in the collected fluid, but AMP did not. In S1 and S2 segments, none of the 14C in the bathing solutions could be identified and no adenosine was found. Of the small amounts of 14C found in bathing solutions from S3 segments, about 27% appeared to be adenosine, the rest were inosine and hypoxanthine or unidentified metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Determinants of hospital charges for coronary artery bypass surgery: the economic consequences of postoperative complications.

This is a prospective study of 500 consecutive patients having coronary artery bypass surgery; mean hospital charge from time of surgery to discharge was +11,900 +/- 12,700. Multiple regression analysis was performed using preoperative variables and postoperative complications. No preoperative clinical feature was a significant predictor of higher average charge. Sternal wound infection (p = 0.0001), respiratory failure (p = 0.0001) and left ventricular failure (p = 0.017) were associated with higher average hospital charge. The absence of any complication predicted a lower average charge, and postoperative death (4.4 +/- 4.5 days after surgery) was also associated with lower average charge. A cost equation was developed: hospital charge equalled $11,217 + $41,559 of sternal wound infection, + $28,756 for respiratory failure, + $5,186 for left ventricular failure, - $1,798 for no complication and - $6,019 for death. Recognition of the influence of complications on charges suggests that low average charges can only be achieved by surgical programs with a low complication rate.

Aged↗

Recurrent bacterial endocarditis in a man with tetralogy of Fallot: earliest recurrence on record.

Enterococcal endocarditis occurred in a young man with tetralogy of Fallot who had just completed therapy for staphylococcal endocarditis. The patient had a transient reversal of flow through the ventricular septal defect during staphylococcal endocarditis with lung abscesses and had persistently elevated teichoic acid antibody titers during the second episode caused by enterococcus. Our review of the literature on recurrent infective endocarditis indicates that our case represents one of the shortest intervals of recurrence with a second organism.

Adult↗

Control of artifacts in plasma adenosine determinations.

The literature concerning the role of adenosine (ADO) in physiology reveals no agreement about plasma ADO concentrations and suggests two main sources of error in these determinations: rapid ADO uptake by red blood cells or rapid ADO production from ADO nucleotides, which may be released by any cell lysis or platelet aggregation during plasma preparation. We therefore studied ADO concentrations in plasma from normal human forearm venous blood. ADO was determined by a high-performance liquid chromatographic procedure with a sensitivity of 3 nM (original plasma). Observed ADO concentrations ranged from 894 nM to 8.2 nM depending on the conditions of plasma preparation. In plasma prepared in plastic tubes from 4.5 ml of blood drawn into a plastic syringe containing 1.5 ml of an isotonic stopping solution (pH 7.4) containing heparin (60 units ml), dilazep (40 microM), EGTA (40 mM, EDTA (40 mM), erythro-9-(2-hydroxy-3-nonyl) adenine (40 microM), and alpha, beta-methylene adenosine-5'-diphosphate (525 nM), the plasma ADO concentration was 13.3 +/- 1.88 nM (SE) after correction for a simultaneous ADO recovery determination. The mean ADO recovery was 78% +/- 3.39. The mean plasma ADO concentration found by this method of collection and preparation is lower then reported by others. Proper collection methods are required to avoid artifacts when determining plasma ADO concentrations.

Adenosine↗

Endogenous intrarenal adenosine preserves renal blood flow in one-kidney, one clip rats.

Intrarenal adenosine concentration is threefold greater in the one-kidney, one clip hypertensive rat compared with normotensive animals. Since exogenously administered adenosine may increase renal blood flow by direct vasodilation, inhibition of renin release, or prejunctional interruption of adrenergic neurotransmission, these studies examined whether endogenous intrarenal adenosine maintains renal blood flow distal to renal arterial stenosis. Administration of theophylline, which blocks the direct vasodilating effect of adenosine and antagonizes the inhibitory effect of adenosine on renin release and sympathetic neurotransmission, resulted in marked renal vasoconstriction in one-kidney, one clip hypertensive animals. This theophylline-induced renal vasoconstriction was markedly attenuated by angiotensin II blockade with saralasin and was unchanged by renal denervation or beta 1-adrenergic blockade with atenolol. These findings indicate that the marked renal vasoconstriction in one-kidney, one clip hypertension during theophylline administration is mainly mediated by angiotensin II, is to a lesser degree due to inhibition of adenosine-induced vasodilation, and is independent of sympathetic influences. These data suggest that endogenous interstitial adenosine preserves renal blood flow in one-kidney, one clip hypertension mainly by inhibiting renin release.

Adenosine↗

Afferent renal nerves and hypertension.

Adenosine-sensitive nerve endings have been found in the renal pelvis which when stimulated increase sympathetic activity producing hypertension. When urinary adenosine concentration is lowered by intrarenal infusion of adenosine deaminase in one-kidney one-clip rats, peripheral sympathetic nervous system activity and arterial pressure decrease if the renal nerves are intact. These data suggest that a stimulus for afferent renal nerve activity in one-kidney, one-clip hypertension is intrarenal adenosine. This intrarenal adenosine hypertensive reflex was examined further observing the responses to renal pelvic xylocaine infusion, selective renal deafferentation, adrenal demedullation and spinal cord transection (T6). The intrarenal adenosine hypertensive reflex was interrupted by renal pelvic xylocaine infusion, renal deafferentation and adrenal demedullation in normotensive and one-kidney, one-clip hypertensive animals. The intrarenal adenosine hypertensive reflex persisted after spinal cord transection (T6). These data support the concept that adenosine-sensitive intact afferent renal nerves located in the renal pelvis enhance sympathoadrenal activity resulting in the maintenance of one-kidney, one-clip hypertension and that this intrarenal adenosine-hypertensive response may occur as a spinal-level reflex in the rat.

Adenosine↗