Limited value of 99mTc depreotide single photon emission CT compared with CT for the evaluation of pulmonary lesions.

OBJECTIVES: A contrast-enhanced multidetector CT (MDCT) scan is the first choice examination when evaluating patients with suspected lung cancer. However, while the clinical focus is on CT, research focus is on molecular biological methods whereby radiolabelled pharmaceuticals are injected into participants and target malignant lung tumours. We examined whether a contrast-enhanced MDCT scan supplied with an additional non-contrast enhanced high-resolution CT scan, or a newer but more expensive (99m)Tc depreotide single photon emission CT (SPECT) scan, was the better first-choice examination for the work-up of pulmonary lesions. Furthermore, we examined whether a (99m)Tc depreotide SPECT scan was an appropriate second-choice examination for patients with indeterminate lesions. METHODS: 140 participants were included in the analysis. CT images were given a malignancy potential rating of 1, 2 or 3 with higher rating being indicative of disease. (99m)Tc depreotide SPECT images were graded either positive or negative. Histopathology and CT follow-up were used as reference standard. Sensitivity, specificity and diagnostic accuracy were calculated. RESULTS: Overall sensitivity, specificity and diagnostic accuracy of CT were 97%, 30% and 84%, respectively. Overall sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 94%, 58% and 76%, respectively. For indeterminate lesions sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 71%, 68% and 69%, respectively. CONCLUSION: Both CT and (99m)Tc depreotide SPECT made valuable contributions to the evaluation of pulmonary lesions. (99m)Tc depreotide SPECT results were not superior to CT results and did not contribute further to the diagnostic work-up. Regarding indeterminate lesions,( 99m)Tc depreotide SPECT sensitivity was too low.

Effects of losartan on diabetic maculopathy in type 2 diabetic patients: a randomized, double-masked study.

OBJECTIVE: Diabetic maculopathy (DMa) is a leading cause of visual loss in the western world. Preliminary studies have suggested that angiotensin converting enzyme inhibitors might be effective in preventing the progression of diabetic retinopathy, but no studies have quantitatively assessed the effect of this treatment on macular oedema in patients with DMa. We evaluated the effect of treatment with the angiotensin II receptor antagonist losartan on macular oedema and hard exudates in patients with an advanced stage of DMa. DESIGN: Randomized, placebo-controlled, double-masked and parallel-group trial. SETTING: Academic medical centre. SUBJECTS: Twenty-four type 2 diabetic patients with DMa. INTERVENTION: Subjects were randomly assigned to a 4-month treatment with either losartan (50 mg o.d.) or placebo. MAIN OUTCOME MEASURES: (i) Degree of macular oedema as estimated by optical coherence tomography scanning of the retina; (ii) fundus photography and flourescein angiography; (iii) 24-h ambulatory blood pressure (BP); (iv) urinary albumin excretion (UAE); and (v) transcapillary escape rate of albumin (TERalb). RESULTS: Central retinal thickness increased from 244 +/- 16 to 256 +/- 31 microm in the losartan group, whilst there was no change in the placebo group (245 +/- 36 microm vs. 242 +/- 30 microm), P = 0.017. Day BP were lowered in the losartan group (from 144/83 +/- 17/10 to 138/78 +/- 20/11 mmHg) compared with the placebo group (140/81 +/- 14/5 to 139/82 +/- 13/9 mmHg), P = 0.27 for systolic and P = 0.009 for diastolic BP. Importantly, there were no changes in night BP in any of the groups. We found no changes in the number of hard exudates, semiquantitative retinopathy grade, visual acuity, UAE, or TERalb in any of the groups. CONCLUSIONS: Type 2 diabetic patients with maculopathy do not seem to benefit from short-term treatment with losartan (50 mg once daily) as far as retinal thickness is concerned, as this dose may increase retinal thickness in the central macular area. Long-term studies are required to assess the clinical implications of these findings.

Patients with ovarian cancer have elevated (51)Cr-EDTA plasma clearance early post-operatively.

Plasma clearance of (51)Cr-EDTA (Clp(EDTA)) is widely used to determine glomerular filtration rate prior to carboplatin based chemotherapy. We have observed that many patients with ovarian cancer have elevated Clp in the early post-operative phase compared to later phases. The purpose of this study was to examine whether this observation reflects a systematic difference. We retrospectively analysed data from 53 patients who had undergone surgery for ovarian cancer. Twenty-six patients had Clp(EDTA) measured early after the operation (mean, 8 days (range, 3-16 days)) (early group), and 27 patients had Clp(EDTA) measured late post-operatively (mean, 32 days (range, 19-48 days)) (late group). Clp(EDTA) values was measured before the first, third and fifth course of chemotherapy. Additionally, age, height, weight, cancer stage, ascites and tumour histology were noted. Mean Clp(EDTA) in the early group was significantly higher than in the late group (104+/-4.4 vs 89+/-3.5 ml.min(-1) per 1.73 m(2); P =0.005). Clp(EDTA) declined significantly in the early group from the first measurement after the operation until measurement before the third course of chemotherapy but remained constant in the late group. Clp(EDTA) was not correlated to ascites, cancer stage or tumour histology. It is concluded that patients with ovarian cancer have significantly higher Clp(EDTA) in the early post-operative phase than similar patients with Clp(EDTA) measured late post-operatively.

Partial unilateral ureteropelvic junction obstruction induced in 2-week-old piglets.

PURPOSE: We examined effects on kidney function and morphology of a partial ureteropelvic junction obstruction induced late in the postnatal nephrogenesis period of the pig. We compared the results to a similar study on pigs with obstruction induced early in the nephrogenesis period. MATERIALS AND METHODS: A total of 20 14-day-old pigs were included in the study. Fifteen animals were randomized to partial unilateral obstruction and 5 were sham operated. Kidney function and morphology were analyzed regarding glomerular filtration rate, renographic functional share and total kidney volume at the age of 4, 12 and 24 weeks. RESULTS: At age 4 weeks hydronephrosis was found in all obstructed kidneys included in the study. Four obstructed kidneys had renographic functional share 40% or greater and 1 deteriorated to less than 40% at 24 weeks. A total of 11 obstructed kidneys had a functional share less than 40%, 5 increased to a share greater than 40% at age 24 weeks and 3 had decreasing share from age 4 to 24 weeks. Single kidney glomerular filtration rate of the contralateral kidneys was significantly increased at all ages. Volume of the contralateral kidney was significantly increased at age 4 and 12 weeks. CONCLUSIONS: The variability and course of renographic functional share in kidneys subjected to partial obstruction at age 2 weeks was similar to findings obtained in pigs obstructed at age 2 days. In contrast to these our study showed compensatory increase in function and size of the contralateral kidney, suggesting that contralateral compensation is an ability gained late in the nephrogenesis period.

Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial.

Octreotide seems to have a beneficial effect on variceal bleeding, and long-term administration for the prevention of rebleeding is currently being evaluated. Experimental studies have suggested a beneficial effect of chronic octreotide treatment on renal function, while clinical studies have shown variable effects. Twenty-five cirrhotic patients with portal hypertension were randomized in a double-blind design to placebo or a single subcutaneous dose of a long-acting formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were performed before dosing and repeated after 30 days. The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P <.01) and an increase of IGF binding protein 1 (P <.05) were demonstrated. No effect of octreotide was observed on GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P <.01) was observed after treatment with octreotide-LAR. It is concluded that in spite of increased arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics and tubular function in clinically stable cirrhotic patients with portal hypertension.

Protein binding of 99Tcm-DTPA compared with other GFR tracers.

99Tcm-Diethylenetriaminepentaacetic acid (99Tcm-DTPA) has been postulated to be more bound to plasma proteins than are other radiopharmaceuticals used for measurement of glomerular filtration rate (GFR). The results of protein binding experiments are, however, highly related to methodology. The aim of the present study was to compare the protein binding of the 99Tcm-DTPA preparation we use in our daily routine with that of the other five 99Tcm-DTPA preparations available and with other GFR tracers by using the same ultrafiltration method. Protein binding was studied in vitro after incubation in donor plasma and in vivo after single injection in patients. A correction for the uneven distribution of ultrafiltrable ions ('Donnan effect') was included. Quality control of six 99Tcm-DTPA preparations performed with thin layer chromatography showed a high labelling efficiency (96.2-99.9%). The in vitro protein binding ranged from 9.25% to 11.12%. The in vitro protein binding of 99Tcm-DTPA was not significantly different from that of 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) and 125I-iothalamate (10.99% vs 12.15%, and 9.55%). There was no difference in the in vivo protein binding of 99Tcm-DTPA 5 and 40 min after injection (13.28% vs 12.58%), and there was no difference in the protein binding of 99Tcm-DTPA and 51Cr-EDTA (12.93% vs 12.54%). In conclusion, in vitro and in vivo protein binding of 99Tcm-DTPA was 10-13%. The protein binding was not different from the binding of 51Cr-EDTA and 125I-iothalamate.

99mTc-Sestamibi SPECT is a useful technique for viability detection: results of a comparison with NH3/FDG PET.

OBJECTIVE: Assessment of myocardial viability by 99mTc-Sestamibi Single Photon Emission Computerized Tomography (SPECT) has been suggested as a more readily available and cheaper alternative to Positron Emission Tomography (PET) with 13N-ammonia (NH3) and 18F-fluoro-deoxy-glucose (FDG). We hypothesized that a semi-quantitative evaluation by SPECT could delineate myocardial viability with an acceptable concordance to PET. DESIGN: Fifty patients (age 57+/-7 years; ejection fraction 28 +/- 8%), with ischemic cardiomyopathy, underwent SPECT and PET imaging in random order. Viability by SPECT was defined as a defect size <50% of the segment area, or a defect representing > or =50% of the segment but with a mean activity > or =50% of peak activity. PET viability was defined as a perfusion score >2 and FDG score < or =2 (five-point scale, 0 = normal, 4 = absent activity). RESULTS: By segmental comparison to PET. SPECT yielded a sensitivity and specificity of 87% and 82% for detection of viable myocardium. The positive and negative predictive values were 96% and 58%, respectively. CONCLUSION: In patients with severe ischemic cardiomyopathy 99mTc-Sestamibi SPECT can delineate viable myocardium with an acceptable segmental concordance to NH3/FDG PET.

A 14-year follow-up of conservative treatment for vesico-ureteric reflux.

OBJECTIVE: To determine renal function in patients with vesico-ureteric reflux (VUR) during 14 years of conservative treatment (no surgery). PATIENTS AND METHODS: Sixty patients with VUR were consecutively included between 1981 and 1982. The degree of VUR was determined by conventional voiding cysto-uretherography (VCUG) after 3 months of prophylactic antibiotics. The VUR was grade I-IV, with grades III and IV characterized as high-grade VUR. In all patients, any urinary tract infections and bladder-urethral dysfunction were treated. Renal function and reflux were monitored by renal and bladder scintigraphy using 123I-hippuran and the glomerular filtration rate (GFR) was determined using the plasma clearance of 51Cr-ethylaminediamine tetra-acetic acid. RESULTS: Of the 60 patients who entered the study, 51 were followed for a mean of 13.7 years; nine patients were lost to follow-up. None of the patients underwent antireflux surgery. All patients were in good health and normotensive (except two with borderline hypertension). Of the 51 patients 21 had low-grade, 21 unilateral high-grade and nine bilateral high-grade reflux. In those with low-grade reflux both the mean renal split function on the most refluxing kidney and the GFR remained stable during the whole monitoring period. Eighteen patients who had a persistent reduction in renal split function or initially had had a significantly reduced functional share to the most refluxing kidney had their GFR re-assessed in adolescence. However, the body surface-corrected GFR remained constant. Total GFR and single kidney GFR increased significantly. CONCLUSION: A conservative treatment regimen in patients with VUR can ensure stable kidney function, although kidneys with a lower renal function at referral seem to have an impaired functional growth potential.

Renal functional outcome in unilateral hydronephrosis in newborn pigs.

PURPOSE: We followed the course of neonatally induced, partial unilateral ureteral obstruction in pigs and established whether early function or morphological evaluation of the hydronephrotic kidney is predictive of outcome. MATERIALS AND METHODS: In 25 piglets unilateral partial ureteropelvic obstruction was induced 2 days after birth, while 11 underwent sham operation. Only obstructed kidneys with significant dilatation at 4 weeks were included for further study. Renal function was assessed on renography using (99m)technetium-diaminetriaminepentaacetic acid differential uptake. According to the plasma clearance of (99m)technetium-diaminetriaminepentaacetic acid the glomerular filtration rate was determined at ages 4, 12 and 24 weeks. Kidney morphology was studied in parallel by magnetic resonance imaging. RESULTS: A total of 12 obstructed kidneys with grade 3 or 4 hydronephrosis fulfilled study inclusion criteria. Of 6 kidneys with a functional share of 40% or greater at age 4 weeks 2 deteriorated to less than 40% at 24 weeks, while 4 of 6 with a share of less than 40% at age 4 weeks improved to greater than 40% at 24 weeks. The single kidney glomerular filtration rate at 4 weeks did not correlate with that at 12 or 24 weeks but the rate at 12 weeks correlated with that at 24 weeks (r2 = 0.8140, p <0.001). Neither relative volume of the obstructed kidney nor length of the contralateral nonobstructed kidney correlated with functional share of the obstructed kidney at any age. CONCLUSIONS: Early evaluation of kidney function or volume, or contralateral kidney length did not predict the outcome of neonatally induced unilateral hydronephrosis in pigs.

Myocardial perfusion imaging in breast cancer patients treated with or without post-mastectomy radiotherapy.

PURPOSE: To assess the occurrence and location of myocardial perfusion defects in left-sided mastectomized breast cancer patients, treated with or without postoperative radiotherapy according to the guidelines from the Danish Breast Cancer Cooperative Group (DBCG). PATIENTS AND METHODS: Seventeen left-sided breast cancer patients, with a median age of 59 years (range, 47-75 years), randomized to post-mastectomy irradiation plus systemic treatment, or systemic treatment alone, were examined after a median follow-up of 7.9 years (range, 6.0-12.2 years). The chest wall and the ipsilateral internal mammary nodes had been treated through two anterior-shaped electron fields, and the electron energy was chosen according to chest wall thickness, measured individually by ultrasound. The median absorbed dose was 50 Gy in 25 fractions, with 5 fractions/week. Information on clinical history was obtained and symptoms of ischemic heart disease (IHD), as well as major risk factors, were recorded. All patients had a physical examination, blood chemistry, electrocardiogram (ECG), chest X-ray and myocardial perfusion imaging by sestamibi-single photon emission computerized tomography (SPECT). SPECT-scanning was performed as a rest/dipyridamole 2-day protocol. The evaluation of regional myocardial perfusion was based on scintigrams using a 20-segment model. RESULTS: There was no significant difference between the scintigraphic findings in the two groups. Four of ten irradiated patients and four of seven non-irradiated patients showed scintigraphic defects. An anterior defect was found in one non-irradiated patient. CONCLUSIONS: This study does not indicate that the described radiotherapy technique induces detectable coronary artery disease. However, the small number of patients does not allow strong conclusions to be drawn.

Plasma clearance of 99Tcm-MAG3: accuracy of five single-sample methods.

The aim of this study was to compare the accuracy of five single-injection, single-sample methods for the assessment of plasma clearance of 99Tcm-MAG3 in adults. In 51 patients, a reference plasma clearance was determined on the basis of 16 blood samples. It ranged from 13 to 313 ml.min-1. In patients with a plasma clearance less than 75 ml.min-1, there was a large difference between the clearance obtained by a single-sample method and the reference method. Thus single-sample methods should not be used with these patients. In patients with a plasma clearance higher than 75 ml.min-1, the relative difference was (mean +/- s): 6.07 +/- 9.96% (Russell et al., 1989), 14.22 +/- 8.08% (Müller-Suur et al., 1991), 7.29 +/- 6.21% (Bubeck et al., 1992), 6.64 +/- 7.71% (Russell et al., 1996) and 17.39 +/- 7.39% (Piera et al., 1997). Reference clearance was overestimated by all five single-sample methods, especially by the methods of Müller-Suur et al. and Piera et al. The smallest standard deviation was obtained using the method of Bubeck et al. This method is recommended for use in patients with a plasma clearance greater than 75 ml.min-1.

Functional significance of recruitable collaterals during temporary coronary occlusion evaluated by 99mTc-sestamibi single-photon emission computerized tomography.

OBJECTIVES: The present study evaluated the impact of recruitable collaterals on regional myocardial perfusion measured by 99mtechnetium (Tc)-sestamibi single-photon emission computerized tomography (SPECT) during temporary coronary occlusion and related these estimates to the coronary wedge pressure and electrocardiographic (ECG) ST-segment changes. BACKGROUND: Clinical variables (angina and ECG changes) and intracoronary flow and pressure recordings have indicated a protective role of recruitable collaterals on myocardial perfusion during percutaneous transluminal coronary angioplasty (PTCA). METHODS: Thirty patients (mean age 55 years, SD 9; 20 men) with stable angina pectoris and proximal nonocluding single-vessel left anterior descending coronary artery (LAD)-stenosis scheduled for PTCA were included. Visualization of recruitable collaterals by ipsilateral and contralateral contrast injection, registration of coronary wedge pressure and injection of 99mTc-sestamibi during 90-s LAD occlusions were undertaken. A rest perfusion study was performed within four days before PTCA. As an estimate of the severity of regional hypoperfusion during occlusion, an occlusion/rest count ratio was calculated (mean defect pixel count during occlusion divided by mean pixel count in identical regions at rest). RESULTS: The scintigraphic occlusion/rest count ratio was higher in patients with recruitable collaterals (n = 16), 67 +/- 11%, compared to patients without collaterals (n = 14), 60 +/- 6% (p < 0.05). The occlusion/rest count ratio correlated with the coronary wedge pressure (R2 = 0.34; p < 0.001). The occlusion/rest count ratio was lower, 61 +/- 6%, in patients with ST-segment elevation (n = 23) versus 74 +/- 9% in patients without ST-segment elevation (n = 7) (p < 0.0001). CONCLUSIONS: Using 99mTc-sestamibi SPECT imaging during brief episodes of coronary occlusion, the severity of regional myocardial hypoperfusion was reduced by the presence of recruitable collaterals in a selected patient population with proximal LAD stenoses. Our results demonstrate a protective effect of recruitable collaterals on myocardial perfusion during temporary coronary occlusion.

Clearance and renal extraction of technetium-99m-L,L-ethylenedicysteine, I-131-ortho-iodohippurate and I-125-iothalamate in pigs.

99mTc-L,L-ethylenedicysteine (99mTc-EC) has been proposed as a 99mTc-labelled alternative to radio-iodinated ortho-iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single-injection plasma clearance technique in pigs. 99mTc-EC, 131I-OIH and 125I-iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of 99mTc-EC and 131I-OIH (175 +/- 9 versus 178 +/- 8 ml min-1, P = 0.43), whereas the difference between the total plasma clearance of 99mTc-EC and 131I-OIH was highly significant (268 +/- 16 versus 185 +/- 9 ml min-1, P = 0.0001). 99mTc-EC had a significant hepatic clearance of 83 +/- 10 ml min-1 whereas the hepatic clearance of 131I-OIH was negligible. Renal plasma extraction of both 99mTc-EC and 131I-OIH decreased significantly between 2 and 240 min post-injection from 0.85 to 0.45% for 99mTc-EC and from 0.93 to 0.57% for 131I-OIH. Red blood cell binding of 99mTc-EC and 131I-OIH was 6.1% and 20%, respectively. The protein binding of 99mTc-EC and 131I-OIH was 32% for both tracers. We conclude that 99mTc-EC is not a suitable tracer for measuring renal function by the single-injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.

Clinical assessment of indication for ACE-inhibitor treatment early after acute myocardial infarction.

An investigation was conducted to assess whether an algorithm based on simple clinical information would suffice to classify patients with acute myocardial infarction, with respect to indication for angiotensin-converting-enzyme inhibitor treatment. One hundred consecutive patients with myocardial infarction were prospectively studied. Based on clinical, radiological, electrocardiographic and biochemical information, the patients were classified as having (a) significantly depressed left ventricular function (ejection fraction < or = 40%) justifying treatment with angiotensin-converting-enzyme inhibitors (ACEI), (b) preserved ventricular function (ejection fraction > 40%) making ACEI unnecessary, or (c) indeterminate ventricular function, requiring further examination. Using a blinded design, ejection fraction was determined by echocardiography and radionuclide ventriculography. A clinical assumption of reduced left ventricular function had a predictive value of an echocardiographically determined ejection fraction < or = 40% of 83% (n = 23). Clinical criteria of good ventricular function had a predictive value of ejection fraction > 40% of 96% (n = 24). In these two groups clinical misclassification occurred in five patients with ejection fraction within the range of 39-45%. Left ventricular function was found to be clinically indeterminate in 53 of the 100 patients. Ejection fraction values assessed by radionuclide ventriculography (n = 44) were on average 9.3%-points lower than echocardiographic values. The indication for ACEI can apparently be determined on the basis of readily available clinical information in approximately 50% of patients with acute myocardial infarction.

Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.

Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.

Validity of rapid estimation of glomerular filtration rate in type 2 diabetic patients with normal renal function.

BACKGROUND: Rapid estimation of the renal function is widely used in clinical practice. METHODS: The validity of rapid estimation of renal function as well as long-term changes in renal function from the Cockcroft-Gault formula for estimation of creatinine clearance or from serum creatinine measurements was evaluated against the 51Cr-EDTA plasma clearance technique in 36 type 2 diabetic patients with normal renal function followed for 5.2 (2.7-7.5) (mean (range) years. RESULTS: Compared with 51Cr-EDTA plasma clearance the Cockcroft-Gault formula significantly underestimated glomerular filtration rate by 21%. The degree of underestimation was observed over the whole range of glomerular filtration rate studied and increased with increasing levels of isotopically measured glomerular filtration rates. Serum creatinine was not significantly associated with glomerular filtration rate. The average long-term change in renal function was significantly overestimated by the Cockcroft-Gault formula (-2.8+/-2.3 ml/min/year) compared with the measured rate (-1.5+/-2.5 ml/min/year) (P=0.002). The difference in change rate between the two methods was highest when the measured fall rates were small and tended to disappear in patients with faster fall rates. Changes in serum creatinine correlated significantly, but imprecisely, with the rate of decline of measured glomerular filtration rate (r=-0.48, P=0.003). The variability of the estimated fall rate of renal function was unacceptably high for all approaches. CONCLUSION: Valid estimates of glomerular filtration rate as well as the rate of change in glomerular filtration rate cannot be obtained by estimation of creatinine clearance from the Cockcroft-Gault formula or from serum creatinine concentration measurements in type 2 diabetic patients with normal renal function.

Transcapillary escape rate and albuminuria in Type II diabetes. Effects of short-term treatment with low-molecular weight heparin.

The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TERalb), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enrolled 44 patients in a placebo controlled study to test the effects of 3 week long treatment with low-molecular weight heparin (tinzaparin) on the same variables. BMI, 24 h systolic and diastolic blood pressure, plasma concentrations of triglycerides, fasting glucose, factor VIII, von Willebrand factor (vWf), fibrinogen, alpha-2 macroglobulin, and fibronectin were notably higher in patients with increased albuminuria compared with normoalbuminuric patients, whereas the TERalb was similar in the two groups. TERalb correlated with fasting plasma glucose. UAE correlated more closely than TERalb with 24 h ambulatory blood pressure, vWf, and factor VIII. Urinary albumin excretion rate was unchanged during tinzaparin [28.9+/-5.6 vs 28.1+/-6.0 microg/min (geometric mean (antilog SD)] vs placebo (18.0+/-5.4 vs 17.6+/-5.3 microg/min), and no change was found in TERalb [6.3+/-1.6 vs 6.0+/-1.5%/h (means +/- SD), and 6.3+/-1.5 vs 5.6+/-1.8%/h; tinzaparin versus placebo, respectively]. Only minor changes were observed in blood pressure, lipids, glycaemic control and haemostatic factors. This study shows no correlation between albuminuria and transcapillary escape rate in Type II diabetic patients without overt nephropathy or uncontrolled-blood pressure. UAE is related to markers of atherosclerosis, endothelial injury and dysfunction, and haemostatic factors. Moreover, UAE correlates much more than TERalb with 24 h ambulatory blood pressure, von Willebrand factor, and factor VIII. Finally, short-term treatment with tinzaparin does not change the transvascular or glomerular leakage of albumin. These results indicate that TERalb is not a sensitive marker of microvascular dysfunction in such patients and that factors other than abnormal glycosaminoglycan metabolism may contribute to the vascular damage of these patients.

Chromium-51-EDTA clearance in adults with a single-plasma sample.

UNLABELLED: In 1996, a committee on renal clearance recommended a mean sojourn time-based methodology for single-sample determination of plasma clearance of 99mTc-diethylenetriamine pentaacetic acid (DTPA) to be used on adults if the patient's glomerular filtration rate (GFR) is suspected to be >30 ml/min. The main purpose of this study was to derive a mean sojourn time-based formula for calculation of 51Cr-ethylenediamine tetraacetic acid (EDTA) clearance in adults. METHODS: Two groups of patients with 51Cr-EDTA clearance (Cl) between 16 and 172 ml/min were studied. In Group I (n = 46), reference Cl was determined as a multiplasma sample, single-injection method (ClSM). Sixteen blood samples were drawn from 0 until 5 hr after a single intravenous injection of 51Cr-EDTA. In Group II (n = 1046), reference Cl was determined by the Brøchner-Mortensen four-sample clearance method (ClBM). The plasma time-activity curves of Group I were used to derive two mean sojourn time-based formulas (Formulas 1 and 2) for calculation of a single-sample clearance. Formula 1 was derived from the entire time-activity curve, whereas the derivation of Formula 2 used only the final slope of the time-activity curve. The accuracy of the two formulas and the Christensen and Groth 99mTc-DTPA formula was tested on Group II. RESULTS: Chromium-51-EDTA Cl calculated by Formula 1 was almost identical to the Cl calculated by the reference Cl method (r = 0.982; SDdiff = 5.82 ml/min). Both 51Cr-EDTA Cl calculated by Formula 2 and by the 99mTc-DTPA formula showed close correlation with the reference method (r = 0.976, r = 0.985, respectively) but systematically overestimated GFR for the whole range of clearance values by 3.5 and 3.2 ml/min (p<0.001), respectively. CONCLUSION: It is possible to get an accurate determination of 51Cr-EDTA Cl from a single-plasma sample in adults by the mean sojourn time methodology. The determination is marginally more accurate (p<0.001) if using a formula derived from the entire plasma time-activity curve than from only the final slope. The single-sample formula derived for determination of 99mTc-DTPA Cl tends slightly to overestimate GFR if used to calculate 51Cr-EDTA Cl.

Evaluation of regional myocardial perfusion in patients with severe left ventricular dysfunction: comparison of 13N-ammonia PET and 99mTc sestamibi SPECT.

OBJECTIVE: Positron emission tomography (PET) scanning with 13N-ammonia and 18FDG is well established for the detection of myocardial viability. Due to the limited availability of PET facilities, recent studies have combined technetium 99m sestamibi single photon emission computed tomography (SPECT) with 18FDG PET or 18FDG SPECT. This approach enables simultaneous assessment of regional myocardial blood flow and metabolism and substantially increases the capacity for viability detection. To validate whether 99mTc-Sestamibi SPECT can replace 13N-ammonia PET, we compared these two modalities in patients with severe left ventricular dysfunction due to coronary artery disease. MATERIALS AND METHODS: Thirty-one patients (mean age 57+/-8 years; mean ejection fraction 27%+/-8%) with angiographically verified coronary artery disease were included. In random order, ammonia-PET and sestamibi-SPECT scans were performed. In a 20-segment model of the left ventricle, two blinded observers scored a total of 610 segments on a five-point scale. In a subset of 20 patients, 400 segments were scored twice to evaluate the observer variations of the two techniques. Segmental score differences were used to compare the imaging modalities. The impact on viability detection was assessed by combining the two flow tracers with FDG PET. RESULTS: Segmental comparison of the PET and SPECT studies yielded similar (difference < or = 1) results in 74% of segments, reflecting regional concordance values in the lateral, apical, anterior, septal, and inferior myocardial walls of 86%, 82%, 71%, 66%, and 63%, respectively. The differences in the septal and inferior walls were primarily due to overestimation of perfusion defects by sestamibi SPECT, which yielded a higher proportion of mismatch patterns in those regions. The overall observer variations of the PET and SPECT studies were 7.5% and 5.8%. CONCLUSION: Myocardial perfusion imaging with 13N-ammonia PET and 99mTc-sestamibi SPECT yielded similar results in patients with severe left ventricular dysfunction, except for the septal and inferior regions. In these regions, SPECT tended to overestimate perfusion defects. Hence, attenuation correction should be considered when combining FDG PET and sestamibi SPECT for diagnosing myocardial viability to avoid overestimation of mismatch patterns in those regions.

The hemodynamic impact of diffuse myocardial ischemic lesions: an animal experimental model based on intracoronary microembolization.

In ischemic heart disease, left ventricular function is affected by a diffuse and segmental loss of myocardium. The decline in the incidence of myocardial infarction and improved early revascularization in acute transmural ischemia predict a change in the natural history of ischemic heart disease. It is now believed that, minor ischemic episodes, which are known to induce multifocal myocardial degeneration, will predominate in the near future. The objective of the present study was to develop a clinically relevant experimental model for investigation of the pathophysiological significance of diffuse ischemic myocardial lesions. Cardiac performance was gradually depressed by selective intracoronary microembolization in 13 pigs. Left ventricular function was quantitated by ejection fraction (EF), pulmonary pressure, cardiac output, and derivatives of left ventricular pressure. Left ventricular volume was estimated by epicardial echocardiography, using a new, unbiased stereological volume estimator. A chronic substudy was performed in order to characterize the histological changes and to evaluate the feasibility of establishing a chronic preparation of the model. Embolization induced acute left ventricular dysfunction; left ventricular pressure change decreased from 966+/-274 to 637+/-146 mmHg/s, and early diastolic relaxation from 1403+/-515 to 824+/-344 mmHg/s, respectively. Ejection fraction decreased by 45%+/-5% and cardiac output by 29%+/-11%. End-diastolic volume increased significantly, from 66.1+/-13.2 to 77.0+/-19.4 cm3, and end-systolic volume increased from 35.9+/-13.9 to 52.3+/-7.6 cm3. No change in heart rate or left ventricular filling pressure was observed. Diffuse ischemic myocardial injury was identified after a mean follow-up of 40 days. Intracoronary microembolization induces acute left ventricular dysfunction due to microinfarcts. Increased left ventricular end-diastolic volume is the initial compensatory response to the acute impairment of cardiac performance in nontransmural myocardial ischemia. This model is suitable for the evaluation of the hemodynamic changes secondary to acute and chronic diffuse loss of functional myocardium.