Biomedical subjects

J S Grime

Publications and source records attributed to J S Grime.

At least 19 recordsLinked to original sources

PubMed1993

Observations on the early renal uptake and later tubular metabolism of radiolabelled aprotinin (Trasylol) in man: theoretical and practical considerations.

1. The novel method recently developed to measure renal tubular degradation of filtered proteins in man using radiolabelled aprotinin (Trasylol) has been modified to allow the fate and the significance of the renal catabolism of radiolabelled aprotinin to be determined beyond 24h. 2. Ten renal patients with normal kidney function and variable proteinuria each received two separate intravenous injections of radiolabelled aprotinin, 5.0 mg of 99mTc-labelled aprotinin (40MBq) and 0.5mg of 131I-labelled aprotinin (5MBq). Chromatography (Sephadex-G-25-M) was used to separate undegraded radiolabelled aprotinin from the free isotope in urine and plasma. Renal uptake from gamma-camera images (24h for 99mTc-labelled aprotinin and up to 96h for 131I-labelled aprotinin) and urinary activity (48 and 96h, respectively) were measured. 3. The renal handling of radiolabelled aprotinin was similar with the two isotopes. Chromatography showed that all plasma activity was undegraded radiolabelled aprotinin, and urine activity was only the free isotopic label. 4. Kidney uptake of 131I-labelled aprotinin was prompt, reaching a cumulative maximum of 37.1 +/- 3.0% of dose at 24h, but falling exponentially thereafter to 5.6 +/- 1.0% of dose at 96h. 5. The rate of excretion of the free label in urine, i.e. the metabolic rate of radiolabelled aprotinin, was relatively constant over the first 24h (1.6 +/- 0.09% of dose/h), but then fell in parallel with the diminishing activity over the kidney, i.e. to 1.0 +/- 0.1% of dose/h over 24-48h and to only 0.4 +/- 0.08% of dose/h over 72-96h.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

PubMed1993

Renal tubular protein degradation of radiolabelled aprotinin (Trasylol) in patients with chronic renal failure.

1. The new method developed to measure renal tubular degradation of small filtered proteins in patients with normal renal function, using radiolabelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289-94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or 131I (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 +/- 5.4 (range 11.2-81) ml min-1 1.73 m-2. Activity in plasma and urine was measured over 24-48 h, and chromatography on Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO4- or 131I-. Renal uptake was measured for 99mTc-labelled aprotinin only. 3. The volume of distribution was 20.2 +/- 2.3 litres. Chromatography showed all plasma activity as undegraded aprotinin, and urine activity only as the free labels (99mTcO4- or 131I-). 4. As in patients with normal renal function, activity in the kidney appeared promptly, with 5.7 +/- 2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 +/- 1.6% of dose after 1.5 h, then more slowly to 15.0 +/- 0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1 +/- 2.8% of dose at 24 h. Extra-renal uptake was again insignificant, and both 99mTcO4- and 131I- appeared promptly in the urine, with similar and uniform rates of excretion over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

PubMed1992

Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in man.

1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for the renal tubular turnover of small filtered proteins in man. Lysine potently inhibits tubular peptide uptake, and may thus depress the uptake and metabolism of aprotinin. This was investigated in 14 glomerulonephritic patients with normal renal function and variable proteinuria and in one healthy subject. 2. 99mTc-labelled aprotinin was given intravenously alone, and again 3 days later, immediately after the intravenous administration of 3-6 g of lysine, followed by an infusion over 1 h of 0.3-1.9 g of lysine/kg in individual patients. Activity over kidneys and in urine was measured over 24 h and chromatography was used to separate the undegraded peptide from free isotope. 3. At the low dosage of lysine (< 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake) was unchanged, but early urine samples contained some undegraded aprotinin. Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6 +/- 0.2% of dose/h with no lysine to 0.9 +/- 0.1% of dose/h in the 24 h after lysine, suggesting suppression of tubular aprotinin degradation. Corrected fractional degradation was calculated from the mean urinary excretion of free isotope over a given interval, determined by chromatography, divided by the mean cumulative kidney counts over this same interval, and this also fell after lysine from 0.06 +/- 0.006 to 0.03 +/- 0.006 h-1 (P < 0.005) between 3.75 and 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

PubMed1989

Effects of a somatostatin analogue (SMS 201-995) on the growth and development of hepatic tumour derived by intraportal injection of Walker cells in the rat.

Administration of a long active analogue of somatostatin, SMS 201-995 (2 micrograms subcutaneously twice a day) for 3 weeks after intraportal administration of Walker cells significantly inhibited their growth and development in the liver. This was not due to a direct cytotoxic effect of the analogue on Walker cells whose growth was stimulated in vitro. Furthermore, SMS 201-995 had no effect on the growth of Walker cells implanted into the thigh of rats suggesting that the inhibitory action of the analogue could be confined to tumour cells growing in the liver. Further studies suggested that the inhibitory effect of SMS 201-995 on the growth of Walker cells in the liver could be related to a marked stimulation of the hepatic reticuloendothelial system, by a reduction in portal venous flow in the early stages of treatment or by a combination of these effects. Further studies are required to delineate more precisely the mechanism whereby SMS 201-995 inhibits the growth of hepatic tumour derived from intraportal administration of Walker cells.

Animals↗

PubMed1988

Preduodenal mechanisms in initiating gallbladder emptying in man.

The existence of preduodenal phases of gallbladder emptying in normal volunteers was investigated by evaluating the effect of sham feeding a sandwich (chew and spit) (n = 15), the sight and smell of food followed by sham feeding a cooked meal (n = 15), and gastric distension (intragastric balloon tube) (n = 9) on gallbladder emptying and comparing these responses with those after ingestion of a standard meal (n = 14). A control group given no intestinal stimuli were studied to determine the frequency of spontaneous emptying during fasting (n = 18). 99mTc-EHIDA (2,6 diethylphenylcarbamoylmethyliminodiacetic acid) was used as the biliary tracer. The frequency of gallbladder emptying during fasting was 0.0045/min. Thus, in any 20 min period emptying occurred spontaneously in only about 1 in 11 volunteers. Significant emptying (greater than 5 per cent over 20 min) occurred in 8 out of 15 volunteers after sham feeding a sandwich (P less than 0.001 versus control), in 8 out of 15 volunteers after sham feeding a cooked meal (P = 1.0 versus sandwich sham feed, n.s.), in 6 out of 9 volunteers after gastric distension (P less than 0.001 versus control) and in 14 out of 14 volunteers after meal ingestion. The rate of emptying was significantly greater in the gastric distension and meal ingestion groups compared with other groups (P less than 0.05). However, the emptying rate after sham feeding was not significantly different from spontaneous gallbladder emptying (P greater than 0.05, n.s.). There was no significant difference in time to onset of emptying between the four stimulus groups (P greater than 0.05, n.s.). These results suggest that pre-duodenal stimuli can evoke gallbladder emptying in man, although the precise physiological significance of this phenomenon remains to be established.

Adolescent↗

PubMed1988

Intragastric bile does not perturb gastric emptying of liquids in humans.

Gastric stasis and duodenogastric reflux have each been implicated in the pathogenesis of various upper gastrointestinal disorders. However, the relationship between intragastric bile and gastric emptying has not been explored. In each of nine healthy volunteers (seven men and two women, ages 22-47 years), gastric emptying of 300 ml 10% dextrose labeled with [99mTc]DTPA was measured twice using gamma camera imaging. During one study, 20 min after ingestion of the test meal, 525 mg of freeze-dried, sterilized human T-tube bile dissolved in 20 ml water was introduced into the stomach via a previously sited fine-bore nasogastric tube. Intragastric bile salt concentrations were calculated to be within the range 1.7-2.9 mM. In control studies, 20 ml of water alone was similarly introduced. Emptying at 20 min was comparable for both groups of studies (38 +/- 3% vs 39 +/- 4%; mean values +/- SEM). For each individual study, emptying from 20 to 60 min was well represented by a single exponential function (r = 0.81-0.99). Half-emptying times for curves fitted over this period were similar in the two groups (bile: T1/2 = 18.8 +/- 2.6 min; control T1/2 = 18.8 +/- 1.9 min). These results indicate that intragastric bile, in concentrations similar to those found in patients with gastric ulcer, has no effect on gastric emptying of dextrose in normal subjects.

Adult↗

PubMed1987

Is SPECT of the spleen worthwhile in the evaluation of liver disease severity?

SPECT of the spleen has been performed with 99Tcm-sulphur colloid in 53 patients, and SPECT of the liver has been performed in 57 patients. All patients had histologically proven liver disease and were classified by the degree of severity, Group A-severe, Group B-moderate, Group C-mild. The patients were further classified as cirrhotic and non-cirrhotic. Eight controls were also studied. There is positive though poor correlation between splenic volume and uptake (r2 = 0.55). Splenic volume and uptake are significantly different in Group A patients compared with all other groups (p less than 0.001). They are also significantly different in cirrhotics versus non-cirrhotics and cirrhotics versus controls (p less than 0.001). Splenic SPECT was unhelpful in distinguishing between moderate and mild liver disease. SPECT of the spleen is a time consuming technique but a useful adjunct to liver SPECT in patients with portal hypertension.

Electronic Data Processing↗

PubMed1987

A model of the hepatic perfusion index in the rat.

The hepatic perfusion index (HPI) is an indicator of the relative hepatic arterial to total liver blood flow as measured by dynamic flow scintigraphy. Hitherto, accurate assessment of the HPI in small animals has not been possible because of methodological difficulties. A reproducible method for measuring the HPI by dynamic scintigraphy in rats is described using a rapid intraventricular bolus administration of 0.04 ml 99Tcm sulphur colloid. There was no significant difference between the HPI determined by dynamic scintigraphy and and that calculated from absolute measurements of hepatic arterial and total liver blood flow. These results indicate that the HPI derived by dynamic scintigraphy in the rat is a true estimate of the ratio of the hepatic arterial to total liver blood flow.

Animals↗

PubMed1987

Changes in the hepatic perfusion index during the growth and development of experimental hepatic micrometastases.

Micrometastases were induced in Fisher rats using an intraportal inoculation of 0.2 ml of 8 x 10(7) Walker carcinosarcoma cells. A control group received normal saline. The hepatic perfusion index (HPI) was measured during the growth and development of micrometastases. The HPI at 4 days (0.51 +/- 0.008) and at 6 days (0.65 +/- 0.16) was significantly raised when compared to controls (0.31 +/- 0.07) and at 2 days after inoculation (0.31 +/- 0.06). Hepatic artery flow did not change throughout the study period. However, portal venous inflow was decreased significantly at 4 and 6 days (0.57 +/- 0.16 and 0.55 +/- 0.11) when compared to controls (0.96 +/- 0.34). These results indicate that the change in the hepatic perfusion index is related to a decrease in portal venous inflow. The decrease in portal venous inflow could be a mechanical effect of the micrometastases on intrahepatic blood flow or to increased arteriovenous shunting.

Animals↗

PubMed1987

Hepatic perfusion index in cirrhotic livers--investigation of imaging and analytical procedures.

Dynamic hepatic scintigraphy was performed in a group of cirrhotic patients to evaluate the optimum imaging and analytical procedures necessary for the measurement of the hepatic perfusion index (HPI). Patients were studied in the posterior (n = 19) and the anterior (n = 14), positions, with either 0.2 or 0.5 ml of 99Tcm sulphur colloid administered as a rapid bolus injection. In each subject, three ROIs (small, medium and large) were drawn over the liver, and time-activity perfusion curves were generated. Analytical techniques were developed to allow flexibility in selecting the arterial and portal venous phases of the liver perfusion curve. The quality of the bolus, expressed as the full width at half-maximum of the left ventricular time--activity curve, was independent of the bolus volumes and patient positioning. The dispersion in the data and the inter-observer variation were less in the anterior view using medium and large ROIs, compared with the anterior small ROI and all the posterior ROI sizes. A time delay between liver and kidney arterial phases, if ignored, produced statistically significant effects on the values of the HPI. We conclude that HPI investigations are best performed in the anterior projection. Data analysis using a large liver ROI is preferred, and flexible data-processing techniques are recommended, particularly in the presence of a liver and kidney arterial time delay.

Adult↗

PubMed1987

Induced hepatic arterial blockade by degradable starch microspheres in the rat.

Degradable starch microspheres (DSM, Spherex) have been shown to cause intermittent blockage of hepatic arterial flow and to increase the concentration of regionally injected cytotoxics. The Spherex monitoring system has been developed by Pharmacia, Sweden to establish the correct dose of DSM to optimize hepatic arterial blockade. Groups of normal rats received varying dosages of DSM and co-injected methylene diphosphonate (MDP) in order to reproduce the effect of reduction of passing fraction and marker flow rate as determined by the Spherex monitoring system. A flow reduction and significant decrease in passing fraction was achieved on injection of 4 mg of DSM via the hepatic artery.

Animals↗

PubMed1987

Gall bladder emptying in normal subjects--a data base for clinical cholescintigraphy.

Biliary excretion scintigraphy with a cholagogic test meal may be used to assess patients with suspected disorders of gall bladder motility. The interpretation of results is frustrated, however, by the lack of information about the range of normal responses in a form suitable for comparative analysis. We present the results of 41 gall bladder emptying studies on 32 normal healthy subjects (14 men, 18 women) 30 minutes after intravenous injection of 74 MBq 99Tcm-EHIDA. Gall bladder emptying was provoked by the ingestion of 300 ml milk. Gamma camera scintigraphy was used to plot gall bladder activity against time. Gall bladder emptying occurred within 10 minutes in all men and 12/18 women (p = 0.02). Gall bladder ejection fractions were significantly greater in women (p less than 0.05). Duplicate studies in nine subjects showed good reproducibility (r = 0.959). A plot of mean and (m + 2 SD) values of gall bladder activity against time has been derived. The data provide an estimate of normal gall bladder emptying response, which may be used to aid interpretation of clinical studies.

Adult↗

PubMed1987

Relationship between gastric emptying of a solid meal and emptying of the gall bladder before and after vagotomy.

Little is known of the temporal and quantitative relationships between emptying of the stomach and of the gall bladder in patients with duodenal ulcer before and after vagotomy. A non-invasive double isotope technique was used to investigate these relationships in 27 patients with a duodenal ulcer, before and after operation-truncal vagotomy and pyloroplasty (TV + P; n = 15) and highly selective vagotomy (HSV; n = 12). A further 25 patients were studied after operation (TV + P, n = 20: HSV, n = 5). 99Tcm-EHIDA was used as the biliary tracer and 113Inm bran as the gastric content tracer. In patients with a duodenal ulcer before surgery and in 16 of the 17 patients studied after HSV, the patterns of gall bladder emptying were similar to those previously found in normal subjects. In 60% of patients after TV + P, patterns of gall bladder emptying were altered and the onset of gall bladder emptying was significantly delayed (p less than 0.001) compared with unoperated patients and patients with a HSV. The rate of gall bladder emptying did not correlate with the rate of gastric emptying in any of the patients studied. These observations suggest that TV + P, but not HSV, causes considerable alteration in coordination of gall bladder and gastric emptying.

Duodenal Ulcer↗

PubMed1987

Small bowel resistances and the gastroduodenal brake.

Osmoreceptors in the upper small bowel may delay gastric emptying by inhibiting fundal tone and/or by increasing outflow resistances. In this study we examined the contribution of postpyloric resistances to this braking system. Seven dogs had gastric emptying of 250 ml 15% dextrose, labelled with 99mTc-DTPA, measured by gamma camera imaging (preoperative studies: n = 21). A proximal duodenal cannula was inserted and studies repeated in four modes: with the cannula closed (n = 14); with total diversion of gastric effluent through the cannula (n = 7); with diversion and downstream reinstillation of effluent at a constant rate (n = 14) equivalent to emptying calculated from studies without diversion; and with diversion and total reinstillation of effluent (n = 14). Gastric emptying at 90 minutes was similar in preoperative studies (48 +/- 5% - mean +/- SEM) and in those with the cannula closed (50 +/- 3%). By comparison 'total diversion' produced rapid emptying over 90 minutes (97 +/- 1%; p less than 0.001). Reinstillation of effluent at a constant rate reduced the 90 minute emptying to 59 +/- 6%, and total reinstillation slowed emptying further to 37 +/- 4% (p less than 0.05). Neither reinstillation protocol yielded gastric emptying rates that were significantly different from those in studies without diversion. With total reinstillation, emptying and hence reinstillation rates were more variable, proceeding in a step and plateau fashion. We conclude that canine jejunal osmoreceptor activity is mediated through the stomach, with postpyloric resistances playing little or no role. Gastric emptying curve analysis suggested that increments of rapid small bowel filling provoke exaggerated braking responses.

Animals↗

PubMed1986

A method of radionuclide angiography and comparison with contrast aortography in the assessment of aorto-iliac disease.

Forty-four patients with symptoms of lower limb arterial insufficiency were examined by radionuclide angiography using 99Tcm in vivo red cell labelling and by contrast aortography. The results of the study indicate that radionuclide angiography may well have a useful role to play in determining the type of contrast study most appropriate for delineating the aortic-iliac segment.

Adult↗

PubMed1985

Liver volume and uptake assessment using 123I-BSP tomography.

Liver volume and parenchymal cell uptake of 123I-bromosulphthalein (BSP) has been assessed using the technique of single photon emission tomography (SPET). These results have been compared with a clinical scoring of disease severity and also with results for liver volume and tomographically assessed uptake of 99Tcm-sulphur colloid (SC). Comparisons of volume estimation, geometric mean (GM) uptake curves and a distribution index derived by a mapping technique with both radiopharmaceuticals, show that 123I-BSP tomography is feasible. A short acquisition time is required in order to obtain tomographic information before there is significant biliary excretion. There was a significant difference between the mean percentage uptake of 123I-BSP in the three groups of liver disease severity (P less than 0.002). This technique merits further evaluation in the study of the assessment of functional liver impairment.

Female↗

PubMed1985

Relationship between gastric emptying of solids and gall bladder emptying in normal subjects.

Very little is known about the normal temporal and quantitative relationships between gastric emptying and gall bladder emptying. Using a non-invasive double isotope technique these relationships were investigated in 22 normal healthy adults. 99Tcm EHIDA was used as the biliary tracer and 113Inm labelled bran as the gastric content tracer. Gastric emptying was monoexponential with a t1/2 of 45 +/- 3 minutes (mean +/- SEM). In 15 subjects the gall bladder emptied in relation to eating according to a double exponential function. In these subjects 15.0 +/- 1.6% of gall bladder contents emptied before gastric emptying began. They could be further divided into two clear cut types (p less than 0.001), according to the ejection fraction at 10 minutes and the t1/2 of the first exponential. Emptying of the gall bladder was faster and more of its contents were ejected in subjects with a type I response (n = 9) than in subjects with a type II response (n = 6). In the remaining seven subjects the gall bladder began to empty spontaneously, unrelated to eating. These observations suggest that gall bladder emptying: (a) may have a cephalic phase, (b) can be expressed as a double exponential function, (c) may occur unrelated to eating, (d) which occurs only in relation to eating would appear to be either fast (type I) or slow (type II).

Adult↗

PubMed1984

Histological evaluation of quantitative scintigraphy of the salivary glands in a primate model.

To assess the accuracy with which quantitative scintigraphy reflects the true extent of parenchymal losses in diseased salivary glands, the parotid glands of vervet monkeys were unilaterally subjected to experimental injury and studied by scintigraphy and histomorphometry. The glandular 99Tcm pertechnetate uptake, relative to a standard dose, was expressed as the ratio of operated to unoperated sides. This was compared with the equivalent ratios of the weights of various salivary component tissues, morphometrically determined at necropsy. Our results suggest that uptake levels of 99Tcm pertechnetate are influenced predominantly by the mass of acinar rather than ductal tissue present. Furthermore, in comparisons between scans, because of the inherent variability in the results, quantitative scintigraphy is sensitive only to differences exceeding 25% of the gland mass.

Animals↗