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Biomedical subjects

R C Nelson

Publications and source records attributed to R C Nelson.

At least 19 recordsLinked to original sources

Clinical pharmacology training at the Food & Drug Administration.

Challenged with the clearly demonstrated need for highly trained clinical pharmacologists for new drug development and review activities, the FDA Center for Drug Evaluation and Research (CDER) established an internal Staff College. This organizationally unique and innovative unit addressed the educational needs of both the new and the veteran CDER scientists. A multileveled strategy was conceptualized and implemented as described.

Curriculum

Fast spin-echo imaging of the abdomen during breath-holding: an alternative to RASE and other fast imaging techniques.

We have developed a rapidly acquired T1-weighted spin-echo pulse sequence that uses gradient echo-like parameters of TR 70 ms, TE 10 ms, NEX-1 (SE 70/10/1) with large pulse angles, and presaturation. This sequence yields two images of the abdomen during a comfortable breath-hold of 9 s. Preliminary phantom studies with this sequence demonstrated that peak signal-to-noise ratios occurred at pulse angles of 120 degrees and 135 degrees. Compared to this rapidly acquired sequence, a conventional T1-weighted spin-echo sequence of TR 140 ms, TE 10 ms, NEX-4 demonstrated 2.8 times the signal-to-noise ratio, 2.6 times the liver-spleen contrast-to-noise ratio but only 1.6 times the contrast-to-artifact ratio. When normalized for the imaging time, however, there was little difference in the signal-to-noise and contrast-to-noise ratios, although the SE 70/10/1 demonstrated 2.0 times the contrast-to-artifact ratio. We conclude that for abdominal imaging the SE 70/10/1 is an excellent alternative to RASE and other fast imaging techniques, and, although there are inherently low signal-to-noise ratios, it may be particularly useful when coupled with a paramagnetic contrast agent.

Abdomen

Recovery of vestibular function following hair cell destruction by streptomycin.

Can the vestibular periphery of warm-blooded vertebrates recover functionally from severe sensory hair cell loss? Recent findings in birds suggest a mechanism for recovery but in fact no direct functional evidence has been reported. We produced vestibular hair cell lesions using the ototoxic agent streptomycin sulfate (600 mg/kg/day, 8 days, chicks, Gallus domesticus). Compound action potentials of the vestibular nerve were used as a direct measure of peripheral vestibular function. Vestibular thresholds, neural activation latencies and amplitudes were documented. Eight days of drug treatment elevated thresholds significantly (P < 0.001) and eliminated all but remnants of vestibular activity. Virtually complete physiological recovery occurred in all animals studied over a period of 70 days following treatment. Thresholds recovered within two weeks of drug treatment whereas the return of response morphologies including activation latencies and amplitudes required an additional 6-8 weeks.

Action Potentials

CT during arterial portography: diagnostic pitfalls.

Computed tomography (CT) during arterial portography (CTAP) is an important technique for evaluating the liver before hepatic tumor resection. With this technique, most tumors are of low attenuation compared with that of enhancing parenchyma. At times, low-attenuation lesions are encountered that represent perfusion abnormalities rather than tumor deposits. These perfusion abnormalities can be categorized as (a) those resulting from improper technique; (b) those extending from hilum to capsule (straight-line sign), with or without an obstructing mass; (c) perihilar and periligamentous abnormalities; (d) subcapsular defects (linear or wedge shaped); and (e) those seen with cirrhosis or regenerating nodules. Adjuvant use of delayed CT, magnetic resonance imaging, and intraoperative ultrasound aids in characterization of these nontumorous defects, thereby improving specificity. The authors conclude that when potential candidates are evaluated for hepatic tumor resection, knowledge of the existence of the various diagnostic pitfalls of CTAP and their imaging characteristics is imperative to avoid inadvertent false results.

Angiography, Digital Subtraction

Peritoneal carcinomatosis: preoperative CT with intraperitoneal contrast material.

Thirty-five abdominal computed tomographic (CT) scans of 27 patients with peritoneal metastases from a mucin-producing tumor of the appendix, colon, small bowel, or ovary were retrospectively reviewed. Fifteen scans were obtained of 15 patients after CT with intraperitoneal infusion of contrast material (IP), and 20 scans were obtained of 16 patients with CT without IP. Subsequent exploratory laparotomy revealed that all 27 patients had multi-focal spread of peritoneal metastases. The sensitivity of CTIP and CT without IP for detection of peritoneal metastases at all sites of involvement was 61% and 59%, respectively. For CTIP, the highest sensitivity was in the right subphrenic space (88%), splenic hilum (86%), and left subphrenic space (83%). For CT without IP, the highest sensitivity was noted in the splenic hilum (100%), left subphrenic space (75%), and left paracolic gutter (75%). CTIP and CT without IP had low sensitivity for detection of disease in the greater omentum (50% each) and small-bowel mesentery (38% and 59%, respectively), two areas that had the highest frequency of metastases.

Appendiceal Neoplasms

The frequency and significance of small (less than or equal to 15 mm) hepatic lesions detected by CT.

The purpose of our study was to determine the frequency of detection of small hepatic lesions (less than or equal to 15 mm) in outpatients who had abdominal CT and to assess the significance of these lesions in the presence or absence of known malignant tumors. Contrast-enhanced abdominal CT scans in 1454 patients were reviewed. In 254 patients (17%), hepatic lesions 15 mm or smaller were detected. In 51% of these patients, lesions were judged benign on the basis of other imaging studies, biopsy results, or stability for at least 6 months as shown by CT. Lesions were judged malignant on the basis of progression seen on radiologic studies or biopsy in 22%. The other 27% of the patients had lesions that could not be classified. The majority of patients with small hepatic lesions (82%) were known to have a malignant tumor; in 51% of these patients, lesions were diagnosed as benign. No patient without a known malignant tumor had a small hepatic lesion that was determined to be malignant. Multiple small lesions were more likely to represent malignant disease than were single small lesions. We conclude that small hepatic lesions are common (seen in 17% of our patients), and that there is a high probability that hepatic lesions smaller than 15 mm are benign, even in patients known to have an extrahepatic malignant tumor.

Humans

Persistence of portosystemic collaterals and splenomegaly on CT after orthotopic liver transplantation.

OBJECTIVE: The appearances of portosystemic collaterals and splenomegaly on CT before and after liver transplantation were evaluated. MATERIALS AND METHODS: The records of 54 patients undergoing liver transplantation during a 2.5-year period were reviewed retrospectively. Twenty-five of these patients, in whom both a preoperative abdominal CT scan and a follow-up CT scan at least 1 year after transplantation had been obtained, were clinically well and had had no significant episodes of rejection, severe recurrent hepatitis, or other complication at the time of study. A total of 94 abdominal CT scans in these patients were reviewed to assess changes in portosystemic collaterals and splenic volume. RESULTS: At 6 months after transplantation, portosystemic collaterals at one or more sites were seen in 14 (74%) of the 19 patients scanned at this time in whom collaterals had been seen on CT preoperatively. At 1 year after transplantation, splenic hilar collaterals persisted in 64% of patients, splenocolic ligament collaterals in 50%, retroperitoneal collaterals in 38%, and peripancreatic collaterals in 38% of patients with preoperative varices at these sites who were examined with CT at this interval. Splenic hilar, coronary, and retroperitoneal collaterals were found to persist for up to 4 years after transplantation in the single patient examined at that time. Splenic volume decreased in 94% of patients examined after transplantation, with a mean reduction of 60 +/- 19%. However, the spleen remained significantly enlarged in 56% of patients. CONCLUSION: We conclude that portosystemic collaterals and splenomegaly frequently persist after liver transplantation, but that this finding need not indicate recurrence of hepatic disease or other posttransplantation complications.

Adult

Visual homing using an associative memory.

Homing is the process by which an autonomous system guides itself to a particular location on the basis of sensory input. In this paper, a method of visual homing using an associative memory based on a simple pattern classifier is described. Homing is accomplished without the use of an explicit world model by utilizing direct associations between learned visual patterns and system motor commands. The method is analyzed in terms of a pattern space and conditions obtained that allow the system performance to be predicted on the basis of statistical measurements on the environment. Results of experiments utilizing the method to guide a robot-mounted camera in a three-dimensional environment are presented.

Animals

Magnetic resonance imaging of the pancreas with gadolinium-DTPA.

Gadolinium (Gd)-DTPA was evaluated as a contrast agent for magnetic resonance (MR) imaging of the pancreas at 1.5T. Twenty-five patients were imaged with identical gradient-echo (GE) (TR 47, TE 13, 80 degree pulse angle) and spin-echo (SE) (TR 300, TE 15) MR sequences prior to and following an intravenous bolus of 0.1 mmol/kg Gd-DTPA. Marked pancreatic enhancement was demonstrated on dynamic sequential breath-hold GE images obtained immediately following the Gd-DTPA bolus (116% mean enhancement over pre-Gd-DTPA images). Enhancement decreased but persisted on the SE images obtained approximately 5 and 15 min following the Gd-DTPA bolus (65 and 60% mean enhancement, respectively). Five of the patients had a pancreatic mass. In these five patients, the enhancement of pancreatic tissue resulted in improved conspicuity of the mass. These initial results suggest that pancreatic enhancement occurs following an intravenous bolus of Gd-DTPA and has the potential to improve MR visualization of pancreatic masses.

Adenocarcinoma

Comparison of ultrasonography and oral cholecystography in lithotripsy. II. Determining retreatment.

Both ultrasonography (US) and oral cholecystography (OCG) are being used to evaluate patients after extracorporeal shock wave lithotripsy (ESWL) for gallstones. Criteria for retreatment after the initial ESWL are usually related to the size of the residual fragments. This study examines the efficacy of ultrasound and OCG for determining both the size and number of stone fragments in the gallbladder in an in vitro model and in patients. Ultrasonography and OCG examinations using an in vitro ESWL phantom with ten groups of stones, and on 39 patients, were reviewed independently by three radiologists to determine both the size and number of stone fragments. For the in vitro study, the three readers estimated the correct number of fragments, or the next closest range, in 87% of observations by OCG and in 43% by US. The size of the largest fragment was measured within 1 mm of its actual size in 87% of observations by OCG and 20% by US. Correlation coefficients for the mean measurements of the three readers versus the actual fragment size and number were greater for OCG than for US. For the in vivo study, the three readers agreed in 47% of the OCG versus 32% of US examinations with respect to the number of fragments, and in 65% of OCG compared to 40% of US studies with respect to size of the largest fragment. Multiple statistical analyses demonstrate that these differences are statistically significant. A discrepancy among the readers concerning whether a patient was eligible for retreatment occurred in 15% of OCG as compared to 45% of US studies. Both the in vivo and in vitro studies indicate that there is more interobserver reproducibility for OCG than for US, and that OCG is more reliable in making the decision concerning patient eligibility for retreatment following lithotripsy.

Adult

Hepatic dynamic sequential CT: section enhancement profiles with a bolus of ionic and nonionic contrast agents.

The enhancement characteristics in different portions of the liver during dynamic sequential bolus computed tomography (CT) with iodinated contrast material (DSBCT) were prospectively evaluated in 75 patients by using iothalamate meglumine, iopamidol, and iohexol (25 patients received each agent). After baseline noncontrast CT was performed, DSBCT was performed with a 180-mL intravenous bolus administered at 2 mL/sec. Scanning was started 25 seconds after the bolus was initiated, by using a 3-second scan time and rapid cephalocaudal table incrementation, yielding contiguous 8-mm-thick sections at a rate of nine sections per minute. On postcontrast images, peak enhancement was 115% for iopamidol and 117% for iohexol, both of which were superior to iothalamate meglumine at 95% (P less than .05). After peaking, enhancement then decreased for all three contrast agents, although the decline was more precipitous for iothalamate meglumine. Enhancement on the more caudal sections with both iopamidol and iohexol was superior to that with iothalamate meglumine (P less than .05). The data suggest that the enhancement characteristics for the two nonionic agents may be more optimal for detection of focal hepatic lesions than the ionic agent.

Adult

Extracorporeal shock wave lithotripsy of gallstones: results and 6-month follow-up in 141 patients.

A study of biliary shock wave lithotripsy of gallstones sponsored by Dornier Medical Systems, Munich, began in the United States in May 1988 to evaluate the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) and the need for adjunctive therapy with ursodeoxycholic acid (UDCA). One hundred forty-one symptomatic patients with one to three gallstones 5-30 mm in diameter were randomized to treatment. One week before ESWL, patients were given either UDCA or placebo. This treatment was continued for 6 months. All patients underwent follow-up at predetermined intervals. According to the protocol, re-treatment for fragments larger than 5 mm in diameter could be performed only at 6 weeks; 26 (18%) of the 141 patients were retreated. At 6 months, the stone-free rates for single stones were as follows: patients with noncalcified stones receiving UDCA, 29%; patients with noncalcified stones receiving placebo, 24%; and patients with partially calcified stones receiving either UDCA or placebo, 6%. No significant difference was noted between the UDCA and placebo groups. At 6 months, the stone-free rates in patients with single, noncalcified stones 20 mm or less in diameter were 40% (UDCA) and 32% (placebo), which is superior to rates for those with solitary, noncalcified gallstones 21-30 mm in diameter and those with two or three stones.

Adult

Liver transplant biopsies with a biopsy gun.

The authors evaluated the safety and efficacy of a biopsy gun for performance of image-guided percutaneous biopsy of hepatic allografts in liver transplant recipients. Two hundred fifty-two liver biopsies were performed in 58 transplant recipients over a 27-month period by using this instrument with an 18-gauge needle. Major complications occurred in two of the 252 biopsies (0.8%): One hemopneumothorax necessitated drainage with a chest tube, and one hemorrhage necessitated transfusion. No patient required surgical exploration because of a complication of the biopsy. Specimens were adequate for accurate histopathologic diagnosis in 248 of 252 procedures (98.4%). The authors conclude that image-guided percutaneous biopsy of hepatic allografts with use of the biopsy gun is a safe and accurate method of obtaining hepatic tissue from liver transplant recipients for histopathologic analysis.

Adolescent

Shock wave lithotripsy of gallstones: results and 12-month follow-up in 174 patients.

At the authors' institution, as part of the on-going Dornier National Biliary Lithotripsy Study, 174 patients with gallstones were randomly assigned to receive either ursodeoxycholic acid (UDCA) or placebo for 6 months after undergoing extracorporeal shock wave lithotripsy (ESWL). Six weeks after ESWL, 40 (23%) patients were re-treated for gallstone fragments larger than 5 mm in diameter. No significant difference in the UDCA- and placebo-treated patients was noted. The overall 6- and 12-month stone-free rates for all patients with initially noncalcified stones were as follows: UDCA patients, 31% and 36%, respectively, and placebo patients, 21% and 23%, respectively (P less than .05). In patients with a single, noncalcified gallstone that was at most 20 mm in diameter, the 12-month stone-free rates were as follows: UDCA patients, 60%, and placebo patients, 33% (P less than .01). Patients with noncalcified stones that were 11-20 mm in diameter who were treated with UDCA had a higher rate of stone clearance than placebo patients. At 6 months, the authors' previous study demonstrated no significant difference in the two groups of patients. However, the stone-free rate at 12 months was noted to be significantly higher for patients with a single, noncalcified stone that was at most 20 mm in diameter begun on UDCA than for all other groups of patients.

Adolescent

Manganese dipyridoxyl diphosphate. Effect of dose, time, and pulse sequence on hepatic enhancement in rats.

We used an animal model to investigate the hepatic enhancement characteristics of manganese dipyridoxyl diphosphate (MnDPDP) related to time, dose, and pulse sequence. The contrast doses selected were in the human tolerance range. Using an SE 300/15 pulse sequence, maximum mean hepatic enhancement of 45% (8 mumols/kg) and 58% (12 mumols/kg) over baseline was seen during a plateau maintained between 5 and 50 minutes postinjection in the 8 mumols/kg group, and between 10 and 90 minutes in the 12 mumols/kg group. This plateau was followed by a very gradual decline in hepatic enhancement. Using either 4 or 8 mumols/kg, there was a significant increase in postcontrast hepatic intensity on all relatively T1-weighted pulse sequences (spin echo [SE] 300/15, inversion recovery [IR] 1400/20/400, gradient echo [GE] 47/13/80 degrees, and GE 60/20/30 degrees) except GE 47/13/80 degrees at 4 mumols/kg. At 8 mumols/kg there was superior enhancement, with IR 1400/20/400 and SE 300/15, but at 4 mumols/kg there was no consistently superior sequence. None of the relatively T2-weighted pulse sequences (SE 2000/50, SE 2000/100, or GE 100/30/20 degrees) demonstrated a significant change in hepatic intensity using either dose of contrast. The data suggest that the best combination of dose, pulse sequence, and time for hepatic imaging with MnDPDP is 8 mumols/kg using heavily T1-weighted sequences 5 to 60 minutes following contrast administration.

Animals

Techniques for computed tomography of the liver.

We recommend that the CT technique of choice for routine screening of the liver, especially when there is potential for neoplasia, is dynamic CT using a single monophasic bolus of not less than 150 mL of a 60% iodinated contrast agent and a dynamic incremental package yielding at least 7 sections/minute. Routine use of noncontrast CT prior to dynamic CT is not indicated unless there is suspicion of a hypervascular tumor. We prefer to examine these particular patients with delayed CT 4 to 6 hours after receiving at least 60 g of iodine, as lesion to liver contrast is superior to noncontrast CT. Other indications for delayed CT include indeterminate lesions on dynamic CT or CTAP and perfusion defects on CTAP. In patients who are possible candidates for hepatic tumor resection, more invasive techniques such as CTAP are indicated as they yield the highest sensitivity to focal hepatic lesions, especially small lesions. A combination of CTAP and MR, however, demonstrates a superior lesion detection rate than either modality alone. CT-Lipiodol is a useful technique for detecting and palliating hepatocellular carcinomas, especially in patients with concomitant cirrhosis.

Contrast Media