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Biomedical subjects

W C Klingensmith

Publications and source records attributed to W C Klingensmith.

At least 37 records · Page 2Linked to original sources

Evaluation of intrahepatic cholestasis with radionuclide hepatobiliary imaging.

Since hepatobiliary imaging with 99mTc=labeled iminodiacetic acid derivatives (HIDA) allows relatively separate, sequential measurement of hepatocyte clearance, parenchymal transit, and biliary excretion, these agents should be useful in differentiating intrahepatic cholestasis (IC) from other hepatobiliary disorders. We studied 18 patients with clinical evidence of IC in whom the parenchymal transit time was increased disproportionately to any decrease in hepatocyte clearance. In a second group of 14 patients with hepatocyte disease but without clinical evidence of IC, the average parenchymal transit time was increased less in relation to the average decrease in hepatocyte clearance than in the IC group. In 15 patients with extrahepatic biliary obstruction, the average hepatocyte clearance was disproportionately increased, as in IC, but large-duct obstruction was identified by scintigrams, ultrasound, or computed tomography. These preliminary results suggest that IC can be diagnosed with hepatobiliary imaging.

Adolescent↗

Clinical evaluation of Tc-99m N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate as a replacement for I-131 hippurate: concise communication.

A clinical comparison of Tc-99m N,N'-bis( mercaptoacetyl )-2,3- diaminopropanoate (Component A) (Tc-99m CO2-DADS-A) and I-131 hippurate was conducted in a series of five normal volunteers and 18 patients. Each subject was studied in one session with Tc-99m CO2-DADS-A and I-131-hippurate; digital and analog images were recorded for 30 min and after voiding. In the normal volunteers, digital images with Tc-99m CO2-DADS-A gave a kidney-to-background ratio at 3 min that was greater relative to I-131 hippurate, a leading-edge parenchymal transit time that was similar to I-131 hippurate, and a percent injected dose in the urine at 30 min that was slightly less than I-131 hippurate (p less than 0.05). In patients (serum creatinine 1.0 to 14.3 mg/dl), decreasing renal function impaired excretion of Tc-99m CO2-DADS-A more than that of I-131 hippurate (p less than 0.01). In analog images, Tc-99m CO2-DADS-A always gave superior spatial resolution. No evidence of hepatobiliary excretion was detected with either radiopharmaceutical. We conclude that Tc-99m CO2-DADS-A and similar compounds should be pursued as possible replacements for I-131 hippurate.

Alanine↗

Work in progress: clinical evaluation of Tc-99m-trimethylbromo-IDA and Tc-99m-diisopropyl-IDA for hepatobiliary imaging.

Six healthy individuals and six patients with a wide range of hepatobiliary function abnormalities were studied with Tc-99m-trimethylbromo-IDA; all normal subjects and four of the six patients were also studied with Tc-99m-diisopropyl-IDA. Visual evaluation of analog images demonstrated a greater liver-to-kidney ratio for Tc-99m-trimethylbromo-IDA (p less than 0.01). Sampling for radiopharmaceutical in urine at three hours following injection demonstrated that Tc-99m-trimethylbromo-IDA had a lower renal excretion rate than Tc-99m-diisopropyl-IDA regardless of whether hepatocyte function was normal or abnormal (p less than 0.01). There were no significant differences between the two radiopharmaceuticals in hepatocyte extraction efficiency or hepatic parenchymal transit time. It is concluded that the lower rate of renal excretion and, therefore, greater hepatocyte specificity of Tc-99m-trimethylbromo-IDA justifies expanded clinical trials and may make it the radiopharmaceutical of choice for hepatobiliary imaging.

Adult↗

Diagnosis of biliary atresia with radionuclide hepatobiliary imaging.

Sixteen patients with biliary atresia and 11 patients with neonatal hepatitis were studied preoperatively with either Tc-99m-diethyl-IDA or TC-99m-diisopropyl-IDA. Two parameters were evaluated: hepatocyte clearance and time to appearance of radioactivity in the intestine. Two observers, using a visual grading system of 1 to 4, gave the 16 patients with biliary atresia a hepatocyte clearance grade of 1.7 +/- 0.6 (mean +/- SD); intestinal radioactivity was not seen through 24 hours. The hepatocyte clearance grade of the 11 patients with neonatal hepatitis was 2.1 +/- 0.9 (mean +/- SD) (p greater than 0.05); intestinal radioactivity was seen in nine of 11 patients (p less than 0.001). Using both parameters, 91% of the patients were classified correctly, 4% were misclassified, and 6% were classified as indeterminate; sensitivity and specificity for biliary atresia were 97% and 82%, respectively. Radionuclide imaging with the newer technetium-99m-labeled hepatobiliary radiopharmaceuticals appears promising for the noninvasive diagnosis of biliary atresia.

Bile Ducts↗

Regional blood flow with first circulation time-indicator curves: a simplified, physiologic method of interpretation.

Dynamic computed tomography, digital subtraction angiography, and radionuclide angiography can all be used to evaluate regional blood flow noninvasively. In each case an indicator is injected intravenously and time-indicator curves are generated from regions of interest during the first circulation. Although regional blood flow cannot be determined uniquely from first circulation time-indicator curves, relative transit time to and through the regions of interest and relative regional blood volume in the regions of interest can be measured and related to relative regional blood flow using a modified Stewart-Hamilton equation. However, for precise mathematical calculation, extrapolation of the first circulation data beyond the point of recirculation is required. This extrapolation is inconvenient and difficult to perform accurately and reproducibly. Indices of transit time and regional volume that do not require extrapolation were evaluated in an experimental model. The correlation coefficients between the indices of transit time and volume and the more mathematically precise measurements were 0.99 and 0.95, respectively (p less than 0.01). It is suggested that these indices, which can also be evaluated visually, are useful in interpreting first circulation time-indicator curves in a physiologic manner.

Blood Circulation Time↗

Normal appearance and reproducibility of liver-spleen studies with Tc-99m sulfur colloid and Tc-99m microalbumin colloid.

In order to determine the normal biodistribution and reproducibility of Tc-99m sulfur colloid and Tc-99m microalbumin colloid, each of ten normal subjects was studied twice with each of the two agents. In overexposed delayed analog images of the anterior chest, some thyroid radioactivity was demonstrated in all of 20 microalbumin colloid studies and in none of 20 sulfur colloid studies; lung radioactivity was seen in 19 of 20 (95%) sulfur colloid studies and in none of the microalbumin colloid studies (both p less than 0.001). Delayed digital images showed that the sulfur colloid gave a higher lung-to-heart ratio, a higher lung-to-liver ratio, and a lower bone marrow-to-liver ratio compared with microalbumin colloid (all p less than 0.05). In general, reproducibility was poor for both agents. We conclude that while there are some differences between these two radiocolloids, the differences do not indicate a superiority of the newer Tc-99m microalbumin colloid over the established Tc-99m sulfur colloid for liver-spleen imaging.

Adult↗

Effect of hypophysectomy and hormonal replacement on the uptake of Tc-99m methylene diphosphonate in the metaphysis and shaft of the rat femur: concise communication.

We have investigated the uptake of Tc-99m methylene diphosphonate (Tc-MDP) in the metaphysis and shaft of the rat femur as affected by hypophysectomy and hormonal replacement with growth hormone and thyroxine. Two hours following injection of Tc-MDP, the metaphysis and a specimen of shaft were obtained and the metaphysis-to-shaft radioactivity ratio was measured. By five days after hypophysectomy the metaphysis-to-shaft ratio fell from a control value of 3.8 +/- 0.2 (mean +/- s.e.) to 2.4 +/- 0.2 (p less than 0.05) and remained significantly decreased throughout the 30-day study. When daily hormonal replacement with 0.5 mg of bovine growth hormone and 10 micrograms of thyroxine (both administered intraperitoneally) was given, beginning on the eighth day after hypophysectomy, the metaphysis-to-shaft ratio of Tc-MDP returned to control levels in twelve days. This model demonstrates the effect of growth hormone and thyroxine on the distribution of Tc-MDP, and may be useful as a radiobioassay of net circulating skeletal growth-promoting activity.

Animals↗

Comparative study of 99mTc labeled hepatobiliary agents based on naphthalene and similar ring systems.

A series of 99mTc complexes of naphthalene and naphthalene-like ring systems were evaluated pharmacokinetically as hepatobiliary imaging agents and compared to 131I-rose bengal and 99mTc-N-(2,6-diethylacetanilide)-iminodiacetate in rats and dogs. Although all complexes studied exhibited high specificity for biliary excretion, they varied widely in disappearance rate from blood and in biliary excretion. Complexes with 8-hydroxyquinoline-7-carboxylic acid and hydralazine were relatively lipophilic and were eliminated more slowly than 131I-rose bengal; complexes of iminodiacetic derivatives of naphthalene, N-(2-acetylnaphthyl)iminodiacetic acid N-(2-naphthylmethyl)iminodiacetic acid were more polar and were eliminated much faster. Renal excretion of the complexes was 5.6% or less except for that of the latter compound (18%). Plasma binding ranged from 51 to 98%.

Animals↗

99mTc-DTPA and 131I-hippuran findings in liver transplant recipients treated with cyclosporin A.

The effects of cyclosporin A (CyA), an immunosuppressive agent that is potentially nephrotoxic, on the kidneys of 9 liver transplant recipients were studied with serial 99mTc-DTPA and 131I-hippuran scans. In addition, renal function was determined by measuring serum creatinine levels during the second postoperative week in the 9 unselected CyA-treated patients and, retrospectively, in a control group of 29 liver transplant recipients who had not been treated with CyA and who were selected because they had survived for at least 3 months postoperatively. The early postoperative creatinine level was significantly greater in the CyA group. Eight of the 9 CyA patients showed imaging abnormalities in all preoperative and postoperative studies. Five of the 8 patients showed a pattern similar to that of acute tubular necrosis (relatively preserved perfusion) in at least one study. Lowering the dosage of CyA permitted the continuation of therapy, and all 9 patients are alive after 8 to 14 months.

Bilirubin↗

Cholescintigraphy in extrahepatic biliary obstruction.

The effect of etiology on findings in cholescintigraphy in patients with extrahepatic obstruction was retrospectively evaluated in 29 patients. Of 11 patients with obstruction secondary to cancer, seven (78%) of nine had complete obstruction (delayed images were not obtained in two) and nine (82%) of 11 had a moderate to severe decreases in hepatocyte clearance. Of 12 patients with obstruction secondary to cholelithiasis, only four (36%) had complete obstruction (delayed images were not obtained in one) (p less than 0.05) and all 11 had normal or only midly decreased hepatocyte clearance (p less than 0.05). All five patients with obstruction secondary to pancreatitis had mild partial obstruction and normal or mildly decreased hepatocyte clearance. One patient had partial obstruction secondary to an abscess adjacent to the common bile duct; hepatocyte clearance was mildly decreased. Cancerous and noncancerous causes of biliary tract obstruction produce significantly different findings in hepatobiliary imaging.

Abscess↗

Synthesis and biological evaluation of Tc-99m N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate: a potential replacement for [131I]o-iodohippurate.

A new technetium-chelating agent based on amide and mercaptide donor groups, N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate, was synthesized as an analog of previously described N,N'-bis(mercaptoacetyl)ethylenediamine (DADS). Complexation of Tc-99m with the new chelating group resulted in two components that were separable by high-performance liquid chromatography. The component that eluted first demonstrated high specificity for renal excretion, with over 90% in the urine of rabbits at 35 min, 87% in the urine of mice at 2 hr, and 1.6% or less in the intestines of mice. Excretion was rapid, with the first component equaling or exceeding [131I]o-iodohippurate in the urine of rabbits at all times. The second or latter component demonstrated comparable specificity but slightly slower renal excretion kinetics. Clinical trials with the first component are probably warranted.

Alanine↗

Clinical comparison of Tc-99m N,N'-bis(mercaptoacetamido)ethylenediamine and [131I]ortho-iodohippurate for evaluation of renal tubular function: concise communication.

Recent experiments in normal animals have shown that Tc-99m N,N'-bis(mercaptoacetamido)ethylenediamine (Tc-99m DADS) is a potential technetium-99m-labeled replacement for [131I]ortho-iodohippurate(I-131 Hipp). We compared the two agents in eleven patients with renal transplants (serum creatinine range: 0.9--5.7 mg/dl). Digital and analog images were recorded for 30 min and after voiding. The results indicate that the relative extraction efficiency index of Tc-99m DADS is 76% +/- 3 (mean +/- s.e.m.), that the leading-edge parenchymal transit time of Tc-99m DADS is 137% +/- 6, and that the percentage of injected Tc-99m DADS in the bladder at 30 min is 25% +/- 4 of that of I-131 Hipp (all p less than 0.05). Forty percent of patients showed some hepatobiliary excretion of Tc-99m DADS. We conclude that the biologic properties of Tc-99m DADS are inferior to those of I-131 Hipp and that analogs of Tc-99m DADS should be evaluated in an attempt to find a more suitable technetium-99m-labeled replacement for I-131 Hipp.

Animals↗

Diagnosis of hepatobiliary disease in infants and children with Tc-99m-diethyl-IDA imaging.

Thirteen infants and children from 42 days to 14 years old with hepatobiliary disease underwent Tc-99m-diethyl-IDA hepatobiliary imaging. Five patients had biliary atresia, four had biliary hypoplasia, two had neonatal hepatitis, and there were single examples of alpha-1-antitrypsin deficiency and congenital hepatic fibrosis. Tc-99m-diethyl-IDA imaging accurately differentiated biliary atresia (complete bile duct obstruction) from other forms of childhood hepatobiliary disease by demonstrating no intestinal radioactivity in the former and the presence of intestinal radioactivity in the latter. In addition, two of four patients with biliary hypoplasia had nonhomogeneous parenchymal transit, and the one patient with congenital hepatic fibrosis showed possible intrahepatic cysts. In conclusion, these preliminary data indicate that Tc-99m-diethyl-IDA provides information not previously available with I-131-rose bengal; this information is likely to be useful in the noninvasive evaluation of childhood hepatobiliary disease.

Adolescent↗