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The Lancet - Saturday II October 1975. Sodium iothalamate as an aid to diagnosis of intracranial lesions by computerised transverse axial scanning.

The diagnostic accuracy of computerised transverse axial tomography in conjunction with enhancement of tissue density by sodium iothalamate was assessed in 438 patients, 256 of them having intracranial tumours and 182 having other intracranial disorders. THE 80 X 80 matrix and 20 ml intravenous sodium iothalamate were used in 174 patients, the 160 X 160 matrix and 20 ml sodium iothalamate in 126 patients, and the 160 X 160 matrix and 60 ml sodium iothalamate in 138 patients. The diagnostic accuracy rose from 87% in the first group to 100% in the final group. The proportion of patients showing enhancement of tumour tissue density improved from 64% in the first group to 96% in the third. In the non-tumour patients, excluding those in whom the underlying disease caused no alteration of brain structure or tissue density, the overall accuracy was 96%, being unaffected by the modifications of technique. The enhancement of tissue density in brain abscesses, some cerebral infarcts, and angiomas could be readily distinguished from that seen in tumours.

Astrocytoma↗

Radiation dose enhancement therapy with iodine in rabbit VX-2 brain tumors.

Loading tissue with iodine enhances the radiation dose absorbed from low energy X-rays. In order to test whether this is a useful procedure for treating brain tumors, we infused radiographic contrast media into rabbits carrying VX-2 brain tumors and delivered 15 Gy of 120 kVp X-rays in 3 fractions to the tumor. From CT scans we estimated that the dose enhancement was approximately 30%. The median survival times, after tumor detection on CT, of untreated rabbits, treated with radiation alone, and treated with radiation plus contrast media were 3, 25.5, 38.5 days, respectively. The repeated infusion of contrast media, 3.5 g of iodine per kg of body weight, did not affect kidney function as measured by serum creatinine levels. This method of enhancing radiation dose in brain tumors therefore appears promising.

Animals↗

Design of optimal two-sample bolus injection tests for measuring low plasma clearance rates.

The bolus injection technique is widely used for assessing plasma clearance rates of substances and is based on multiexponential data analysis of multiple concentration measurements. This approach can be simplified to a monoexponential description with only two measurements if intercompartmental mixing occurs at a much faster rate than elimination, i.e. with low plasma clearance rates. In this context initial transients must be ignored because the first measurement time instant affects the accuracy of clearance estimates if mixing is still incomplete. Moreover, measurement noise affects estimation precision which can be optimized by suitable choice of the sampling schedule and of the injected test dose. The aim of this study is to design two-sample bolus injection tests for measuring low plasma clearance rates with preassigned precision and with minimum amount of injected test substance. This paper provides equations for evaluating whether plasma clearance is sufficiently low to allow a monoexponential description of the plasma disappearance curve and for choosing the first sampling time instant. Closed form equations are proposed for determining the optimal test dose and the second sampling time. Result are derived for a particular heteroscedastic measurement noise description, and the problem of robustness with respect to interpatient variability of kinetic parameters is addressed.

Artifacts↗

Cyclosporine therapy for psoriasis: serum creatinine measurements are an unreliable predictor of decreased renal function.

With increasingly widespread use of cyclosporine for the treatment of psoriasis, it is imperative to identify reliable markers of cyclosporine-induced nephrotoxicity. Five patients with extensive psoriasis and no significant preexisting renal disease were treated with oral cyclosporine (average dosage, 5 mg/kg per day; average duration of treatment, 9 weeks). Changes in serum creatinine measurements made immediately before and at the end of treatment were compared with changes in glomerular filtration rate as determined by 125I-iothalamate clearance. During treatment, the average serum creatinine value only increased from 1.0 +/- 0.2 to 1.1 +/- 0.3 mg/dl (+/- standard deviation), whereas iothalamate-based estimates of glomerular infiltration rate decreased from 100 +/- 22 to 63 +/- 37 ml/min/1.73 m2 (p less than 0.02). Simultaneous 125I-iothalamate and 24-hour creatinine clearances were obtained in two patients at the end of treatment and at 2 weeks after cyclosporine therapy. Glomerular filtration rates determined by iothalamate clearance were 14% to 30% lower than those calculated by 24-hour creatinine clearances. Neither serum creatinine measurements nor creatinine clearances (whether calculated or measured) accurately reflect the cyclosporine-induced decline in renal function as determined by glomerular filtration rate. In contrast, 125I-iothalamate clearance is a more accurate measurement of glomerular filtration rate, which provides a sensitive marker for monitoring potential cyclosporine-induced nephrotoxicity.

Adult↗

Ambulatory GFR measurement with cold iothalamate in adults with chronic kidney disease.

BACKGROUND: The purpose of this study is to develop a method that eliminates the use of radioactive agents, reduces the length of inpatient visits, and does not require urine collection for the measurement of glomerular filtration rate (GFR) in adults with chronic kidney diseases (CKD). METHODS: We measured simultaneous urinary and plasma clearance of iothalamate using high-performance liquid chromatography in 30 patients with CKD after a continuous subcutaneous infusion of iothalamate at a rate of 125 microL/h for a 24-hour period. To ascertain whether a steady state was achieved with a 24-hour infusion, in 20 additional patients, we infused iothalamate continuously for 48 hours and measured GFR after 24 and 48 hours. RESULTS: Plasma iothalamate levels and urinary excretion rates obtained after 24- and 48-hour infusions were similar. GFR estimated by plasma clearance (44.4 mL/min; 95% confidence interval [CI], 37.0 to 53.3) was similar to urinary clearance (41.6 mL/min; 95% CI, 34.7 to 50.0) and without bias (average difference, 7%; 95% CI, +18% to -38%; P = 0.866). There also was acceptable agreement between plasma and urinary clearance of iothalamate (coefficient of variation [CV], 19.6% between techniques). Reproducibility of day-to-day plasma continuous infusion clearance technique was less than 12%. There was good agreement (CV, 19.9%) between inulin and renal iothalamate clearances. CONCLUSION: These data show that ambulatory infusion of iothalamate can be used to measure GFR in adults with CKD without the need for urine collections with acceptable precision and without exposure to radioactivity.

Adolescent↗

Effects of recombinant human erythropoietin on renal function in chronic renal failure predialysis patients.

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.

Adult↗

Effect of glycine and hypertrophy on renal outer medullary hypoxic injury in ischemia reflow and contrast nephropathy.

Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% +/- 6% to 41% +/- 9% or 55% +/- 7% with glycine infusion of 75 or 135 minutes, respectively (mean +/- SE, P less than 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% +/- 0% to 12% +/- 6% (P less than 0.05) and from 8% +/- 5% to 49% +/- 8% (P less than 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P less than 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inaccuracy of estimated creatinine clearance for prediction of iothalamate glomerular filtration rate.

The clinical practice of estimating creatinine clearance (Ccr) from a patient's serum creatinine value by use of various nomograms and prediction formulas is widespread. The predictive accuracy of such Ccr estimates as substitutes for measured values of glomerular filtration rate (GFR) has not been determined. In addition, the effect of patient physical parameters on GFR prediction accuracy has not been assessed. To investigate these issues, 500 predicted Ccr values from each of four versions of the formula of Cockcroft and Gault were statistically compared with GFR values measured by sodium iothalamate clearance (Cio) in 394 human subjects representing every level of renal function. We conclude that (1) the original formula of Cockcroft and Gault is an inaccurate predictor of GFR; (2) correction of the formula for patient physical parameters does improve its accuracy for GFR prediction; (3) the best formula is not accurate enough to replace laboratory measurement of GFR; and (4) GFR prediction inaccuracy is more often associated with extremes in patient age, weight, serum creatinine, body surface area, and measured GFR but may occur for any value of each of these parameters.

Adult↗

Effect of indomethacin on the glomerular filtration rate after a protein meal in humans.

The renal response to a protein meal has been characterized by increases in glomerular filtration rate (GFR) and renal plasma flow and decrease in renal vascular resistance. Several hormonal mediators of this response have been proposed, including renal prostaglandins (PGs). We studied ten normal subjects before and after ingestion of indomethacin. All subjects had three 30-minute baseline creatinine and iothalamate clearances measured before and three one-hour clearances measured after an 80-g protein meal. The night before the second test, the subjects took 25 mg indomethacin and 150 mg one hour before the test meal. Urine PG excretion decreased significantly during the second test, from 0.60 +/- 0.23 to 0.30 +/- 0.14 ng/min (P less than 0.01). Initial iothalamate clearance increased from 110 +/- 10 to a mean of 122 +/- 15 mL/min/1.73 m2 (average increase of 12 mL/min/1.73 m2) during the second hour after the test meal. After ingestion of indomethacin, the GFR remained unchanged from a baseline of 101 +/- 9 to 101 +/- 7 mL/min/1.73 m2 (average change of -1 mL/min/1.73 m2). Because the time of peak increase after the meal varied from subject to subject, the maximal increase in GFR after the meal was calculated and found to be significantly less during the second test, 13 +/- 3 v 22 +/- 4 mL/min/1.73 m2 (P less than 0.05). Because PGs can stimulate glucagon secretion and because glucagon has been suggested to mediate the protein-stimulate GFR response, we measured plasma glucagon during both tests; these levels were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat.

Acute renal failure (ARF) can be produced in rats by a combination of insults which augment transport activity and blunt regulatory mechanisms designed to maintain medullary oxygen sufficiency. This type of ARF is characterized by necrosis of medullary thick ascending limbs (mTALs). Uninephrectomized, salt-depleted rats injected with indomethacin (10 mg/kg) develop ARF following the administration of the radiocontrast agent, iothalamate. Furosemide (20 mg/kg, intravenous), administered immediately before the contrast material, attenuated the severity of ARF and reduced mTAL necrosis. Treatment with furosemide and/or normal saline prevented both the decline in renal function and mTAL injury. It is concluded that furosemide and normal saline may ameliorate the course of ARF if administered before radiocontrast.

Acute Kidney Injury↗

Accurate measurement of impaired glomerular filtration using single-dose oral cimetidine.

To improve the validity of a timed creatinine clearance as a measure of glomerular filtration rate (GFR), we investigated whether a single 800-mg dose of oral cimetidine was sufficient to inhibit tubular secretion of creatinine (TScr). Forty-five 3-hour timed creatinine clearances (Clcr) with single 800-mg dose oral cimetidine (TCC) in 17 renal transplant recipients with marked renal function impairment (creatinine 2.0 to 7.1 mg/dL) were compared with simultaneous [125I]-iothalamate GFR (Cliothal). For comparison, 13 timed Clcr without cimetidine (TC), and 36 24-hour Clcr were performed. The TCC was the most accurate: the ratio (mean +/- SD) of TCC:Cliothal was 1.12 +/- 0.02, compared with 1.33 +/- 0.08 for Clcr:Cliothal and 1.53 +/- 1.02 for TC:Cliothal. The difference between Cliothal and TCC was small over the range of GFRs tested (mean +/- 2 SD), 0.9 +/- 2.5 mL/min/1.73 m2. The intraclass correlation (R) for within-subject reproducibility of the TCC in five subjects was 0.8 (95 percent CI; 0.5, 0.9), and in 11 subjects who had at least three GFR determinations over 24 weeks, the TCC was as responsive to change in GFR as Cliothal. There was an inverse relationship between fractional excretion of cimetidine and GFR (r2 = -0.70), suggesting increased tubular secretion of cimetidine with decreasing GFR. In conclusion, a single 800-mg oral dose of cimetidine was effective in inhibiting TScr such that the TCC was an accurate, reproducible, and responsive test of GFR.

Administration, Oral↗

Capillary electrophoresis for the determination of glomerular filtration rate using nonradioactive iohexol.

High-performance liquid chromatography (HPLC) has been used as an alternative to the isotopic method to calculate glomerular filtration rate (GFR). With the HPLC method, serum iohexol or iothalamate levels are measured, and the plasma clearance rate of the compound is used as a surrogate for GFR. However, HPLC is a labor-intensive procedure, which limits its usefulness in the clinical setting. Capillary electrophoresis, a newer technique in which electrophoretic separations are performed in capillary tubes, is easier and faster than HPLC. We used capillary electrophoresis for the determination of serum iohexol levels and the calculation of GFR. Patients underwent a simultaneous 125I-iothalamate clearance test and a plasma iohexol clearance test to determine GFR. Mean GFR (+/-SD) was 70.9 +/- 29.9 mL/min (range, 14.5 to 131 mL/min) in 52 patients as determined by standard iothalamate clearance methods. For iohexol clearance, the correlation coefficient and standard error were 0.93 and 10.9 mL/min, respectively, using capillary electrophoresis compared with the iothalamate method. Capillary electrophoresis is a simple, rapid method that can be used to calculate GFR and provides results at least as accurate as those obtained by HPLC and x-ray fluorescence.

Adult↗

Similar cytogenetic effects of sodium-meglumine diatrizoate and sodium-meglumine ioxithalamate in lymphocytes of patients undergoing brain CT scan.

Cytogenetic effects of two ionic contrast media (CM), Urografin 76% a sodium-meglumine diatrizoate, and Telebrix 38, a sodium-meglumine ioxythalamate, were tested on lymphocytes of patients undergoing brain CT Scan. Both compounds have approximately similar iodine concentrations. Chromosomal aberrations were scored in peripheral lymphocytes obtained from 15 patients undergoing brain CT with either urografin 76% or telebrix 38 before and after examination. Results showed no difference in aberration frequency for patients who underwent brain CT without contrast materials compared to controls. However, injection of CM resulted in a high frequency of chromosomal aberrations which significantly differed from controls (P < 0.05). The effect of urografin 76% appeared to be similar to telebrix 38. Therefore, both CM exhibited clastogenic effects on peripheral lymphocytes in vivo. An increase in chromosomal aberrations due to CM used in this study were similar to that reported for other ionic and non-ionic compounds.

Adolescent↗

Telebrix Gastro in the management of adhesive small bowel obstruction.

BACKGROUND: This study aimed to determine whether an abdominal radiograph 8 hours after ingesting oral Telebrix Gastro is a reliable marker for non-operative management in patients with adhesive small bowel obstruction. METHODS: During a 5-year period (January 1, 1995, through December 31, 2000), 97 patients were admitted for small bowel occlusion due to adhesion with no indication for immediate surgery. All received 100 mL of Telebrix Gastro via gastric tube for small bowel obstruction due to adhesion. If the contrast reached the colon within 8 hours on plain abdominal radiograph, the test was considered to be negative. RESULTS: 126 cases of small bowel occlusions were analyzed due to recurring episodes for 11 patients. The test was negative in 113 cases (89.7%), and in this group, only two patients underwent surgery, the remaining being managed non-operatively. The 13 cases (10.3%) with a positive test for occlusion underwent surgery. The sensitivity, specificity and accuracy of the finding of contrast media reaching the colon as an indicator for conservative treatment were 98%, 100%, and 98%, respectively. CONCLUSIONS: A water-soluble contrast study can be of significant help in the clinical management of patients suspected of having small bowel obstruction.

Adolescent↗