PubMed Health⌕ Search

Biomedical subjects

P Shaffer

Publications and source records attributed to P Shaffer.

9 recordsLinked to original sources
PubMed1989

Hepatic recovery after biliary decompression of experimental obstructive jaundice.

Obstructive jaundice was produced in 11 dogs by common bile duct ligation for 4 weeks, then biliary decompression was performed by bilioenteric anastomosis. Animals were regularly studied over the 2 months after decompression by the following methods: (1) serum biochemistry was monitored; (2) light microscopic changes in serial liver biopsies were graded; (3) the respiratory characteristics of isolated hepatic mitochondria, obtained by open liver biopsy, were studied using an oxygen micro-electrode system; (4) in vivo handling of an hepatobiliary imaging agent (diisopropyl iminodiacetic acid) was studied by dynamic liver scintiscanning. None of these liver assessments were normalized after 7 to 10 days of biliary decompression. Our study suggests that biliary decompression of patients with extrahepatic biliary obstruction requires long periods of time to enable major recovery of the abnormal liver function induced by biliary obstruction.

Anastomosis, Surgical↗
PubMed1989

DISIDA kinetics measure liver function in dogs.

We have investigated the ability of 99Tcm-disofenin (DISIDA) kinetics to measure liver function. Two approaches have been used: first, quantitative analysis of serial liver images, and second, clearance estimation from whole blood concentration-time data. Graded liver dysfunction was produced in 11 dogs over three months by common bile duct ligation and surgical relief of biliary obstruction one month later. The kinetic analysis of serial liver images showed clear abnormalities during biliary obstruction, with calculated rates of liver uptake falling in stages from 11.09 to 5.15 cts s-1 (p less than 0.001), and rates of elimination from the liver from 8.8 to 1.6 x 10(-4) cts s-1 (p less than 0.0001). These parameters paralleled the deterioration and recovery of liver function through the experimental period, and had not fully recovered 7 weeks after relief of biliary obstruction (10.5 and 6.2 x 10(-4) cts s-1 respectively). Serial blood sampling after injection of DISIDA permitted calculation of whole blood disposition rates (for hepatic clearance). Mean values fell from 256 to 67 ml min-1 with chronic biliary obstruction (p less than 0.001), and returned to almost normal (206 ml min-1) 10 days after surgical relief of biliary obstruction. It is clear that the gradual nature of recovering liver function was more sensitively identified by image analysis than serial blood data. Serial liver biopsies showed marked changes following biliary obstruction. These improved over a period of 7 weeks following its relief, when there was still considerable residual abnormality. This work supports the view that hepatic abnormalities caused by biliary obstruction do not recover quickly following its relief. DISIDA kinetics can quantitate both major and minor degrees of hepatic dysfunction, and may prove to be a valuable method to quantitative liver function.

Animals↗
PubMed1988

Pharmacokinetic studies of DISIDA disposition. I. Animal studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced by chronic bile duct ligation (256 vs 58 ml/min, P less than 0.001). Blood levels of radioactivity fell in a biexponential fashion characterized by rapid and slow disposition phases, whose half times were 2.4 and 58 min in normal animals. On 3 occasions, plasma was obtained from 1 animal by exsanguination 35 min after the administration of DISIDA and rapidly transfused into a 2nd animal. The whole blood pharmacokinetics of the second (recipient) animal showed a predominance of the slow disposition phase and a small rapid phase. The hepatic extraction ratio of blood radioactivity was measured in 3 dogs and was high (75%-90%) early after injection of DISIDA, but fell rapidly to remain around 10%. These experiments suggest the presence of two different species in the radiopharmaceutical studied, each being removed from the blood stream by the liver, but at different rates. The contribution of renal clearance to overall whole blood pharmacokinetics was negligible, since three nephrectomized dogs displayed similar pharmacokinetics to normals. Whole blood DISIDA pharmacokinetics are more complex than previously thought but appear to be capable of providing an accurate measure of liver function.

Animals↗
PubMed1988

Pharmacokinetic studies of DISIDA disposition. II. Clinical studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained clearly discriminated 9 normal subjects from 7 patients with severe liver disease causing jaundice--1233 mls/min vs 384 mls/min (P less than 0.002). Nine subjects with liver disease of insufficient severity to cause jaundice also had clearly abnormal DISIDA disposition--642 ml/min (P less than 0.05 for difference to controls). The time activity curves from all subjects showed biexponential elimination of blood activity, with a rapid (T1/2 = 3.8 min) and a slow disposition phase (T1/2 = 75 min) in normals. These curves were fitted by computer to the timed rate of hepatic uptake, simultaneously obtained by gamma imaging over the liver. It was not possible to satisfactorily fit these using a model which assumed distribution of a single compound within two body compartments. However, another which assumed the administration of two radioactive agents satisfactorily fitted the two types of data. This conclusion is consistent with our animal experiments which indicate the existence of two compounds in injected DISIDA with contrasting high and low hepatic extraction efficiency (Fraser et al. 1988). A pharmacokinetic approach to DISIDA disposition can yield quantitative information which discriminates different degrees of liver dysfunction, but the mechanisms involved are more complicated than previously thought, so that further study should permit very precise quantification.

Adult↗
PubMed1987

Histologic and biochemical correlates of left ventricular chamber dynamics in man.

To investigate the relation between left ventricular chamber dynamics in humans and the quantitative analysis of the histologic and biochemical characteristics of left ventricular endomyocardial biopsy material, 15 patients with a wide range of ventricular function were studied. The pressure-volume relation was determined using simultaneous gated radionuclide angiography, echocardiography and micromanometer pressure. The derived chamber dynamics were then compared with quantitative histologic data (percent fibrosis and cell diameter) and adenosine triphosphate content measurements obtained from the left ventricular biopsy specimen obtained at the time of the pressure-volume studies. The measures of systolic function correlated linearly with high energy phosphate content. The adenosine triphosphate/protein ratio (nanomoles) was shown to parallel ejection fraction (r = 0.81), peak ejection rate (r = -0.73) and peak positive maximal rate of rise in left ventricular pressure (dP/dt) (r = 0.79). No correlation was observed between these variables and the percent fibrosis or cell diameter. Variable results were found in comparing the diastolic properties of the left ventricle with the biopsy data. In general, the high energy phosphate content correlated with measures of active relaxation, but not with the passive filling characteristics of the left ventricle. The adenosine triphosphate/protein ratio was linearly related to peak negative dP/dt (r = -0.74) and the peak filling rate (r = 0.76) but correlated less well with other measures of active and passive diastolic filling. No correlation was found between any diastolic variable and the percent fibrosis or cell diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Localization of the site of ventricular premature complexes by radionuclide angiographic phase imaging.

To investigate whether gated radionuclide angiographic phase imaging is useful for visually displaying the origin of ventricular premature complexes (VPCs), 82 patients were studied by gating only VPCs. The VPC "origin" by the scintigraphic method was defined as the area of earliest phase and was compared with that predicted by 12-lead electrocardiographic criteria in all patients and to invasive electrophysiologic mapping in 10. Separating the right ventricle into 3 and the left ventricle into 4 segments, the phase imaging method and the electrocardiographic criteria agreed as to ventricle of VPC origin in 69 patients (84%) and segment of origin within each ventricle in 46 (56%). When baseline ventricular wall motion was analyzed, the 2 methods agreed to the ventricle of VPC origin in 31 of 33 patients (94%) with normal wall motion, 20 of 23 (87%) with segmental wall motion abnormalities and 19 of 26 (73%) with diffuse wall motion abnormalities. Agreement between the 2 methods as to specific segmental localization of the arrhythmia focus was noted in 21 of 33 patients (64%) with normal wall motion, 11 of 23 (48%) with segmental wall motion abnormalities and 12 of 26 (46%) with diffuse hypocontractility. In the 10 patients with endocardial mapping studies, the phase imaging technique confirmed the segment of VPC origin in all 10; the electrocardiographic method was accurate in 8. Thus, gated radionuclide angiographic phase imaging methods may be of value in noninvasively defining the origin of spontaneous VPCs. The visual format allows ready interpretation of the arrhythmia origin, and there may be an advantage to this approach over electrocardiographic morphometric criteria.

Adolescent↗