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Biomedical subjects

R Hickman

Publications and source records attributed to R Hickman.

At least 91 records · Page 5Linked to original sources

The effect of portal diversion upon function of the reticuloendothelial system and upon plasma fibronectin levels.

A previous publication suggested that for 9 weeks after portal diversion in dogs, there were no changes in reticuloendothelial function assessed by measurement of t1/2 or phagocytic index of reticuloendothelial test lipid emulsion. The present study was conducted in rats over 18 weeks. It was observed that the phagocytic index decreased and the t1/2 lengthened at 18 weeks after either portacaval shunt or portacaval transposition and that plasma levels of fibronectin were elevated four- or five-fold after either form of diversion, whilst only being elevated two-fold after sham operation. There was an increase in portacaval shunt rats in liver tissue distribution of administered lipid emulsion when tested between 6 and 12 weeks post-operatively which then returned towards normal. The activity in portacaval transposition and sham-operated rats was unaltered. These studies suggest that the delay in clearance of administered particles in portacaval shunt and portacaval transposition rats is related to the portal diversion rather than to altered blood flow and thus the finding is of relevance in patients with cirrhosis who also have significant portacaval shunting.

Animals↗

Disturbances of reticulo-endothelial function following experimental liver transplantation.

Reticulo-endothelial function was studied in liver-grafted pigs using intravenous carbon clearance at 24 h and 7 days postgraft. Flushing of auto- or allografts with Ringer's lactate and with or without 4-hour storage caused no change in carbon clearance. Flushing of auto- or allografts with Eurocollins solution and with or without 4-hour storage resulted in delayed carbon clearance at 7 days. The changes appeared to be related to the composition of preservation fluid rather than to its volume or temperature, the duration of storage or the development of rejection.

Animals↗

Use of verapamil with conventional immunosuppression after porcine renal transplantation.

It has recently been suggested that the use of calcium channel-blocking agents may improve the results of renal transplantation either by enhancing the immunosuppressive effects of ciclosporin, or by improving posttransplant acute renal failure. In the present study, unlike others, verapamil was administered to the animals for 10 days posttransplant, alone or in conjunction with ciclosporin and/or solumedrol. In the group in which all three agents were given together, there were minimal changes in plasma urea or creatinine for the 10 days after transplantation. However, survival and the histological appearances of the kidneys at autopsy showed no improvement as compared with those in animals treated with cicloporin and steroids. There is thus no evidence from this study to suggest that verapamil could advantageously be added to a clinical immunosuppressive regime.

Animals↗

Serial mixed lymphocyte culture responses in pigs after liver or kidney auto- or allotransplantation.

In order to investigate further the peculiarly limited response of the transplanted pig liver to rejection, this study investigated serial mixed lymphocyte culture (MLC) responses and suppression of phytohaemagglutinin (PHA)-stimulated lymphocytes by serum from transplanted animals. The responses of lymphocytes from liver allografted pigs were compared with those from sham-operated, liver-autografted or kidney auto- or allografted animals for up to 22 weeks postoperatively. Lymphocytes from operated animals were added to cultures of 2 'universal' donors which were not anaesthetised at any time and which remained lymphocyte donors for the period of each operated pig's survival. After liver allograft, a sustained stimulation of MLC responses was noted which contrasted with the minimal random stimulatory activity seen in the other groups. The response was not seen in lymphocytes from animals subjected to liver autograft. There was a surprising variability in the week-to-week MLC tests of individual animals for which no cause could be found. The serum from liver auto- and allografted pigs had suppressive action on the PHA stimulation of lymphocytes. There was no correlation between the length of survival and the intensity of the pre-operative MLC response. Whilst the biochemical data of liver allografted pigs showed evidence of ongoing hepatocyte damage, the histological changes were less obvious especially in the long-surviving group. This study highlights again the ability of unimmunosuppressed pigs to accept liver allograft and seems to associate this with sustained hepatocyte damage and stimulation of the MLC.

Animals↗

Evaluation of Tc-99m-DTPA for renal clearance studies in the pig.

Conventional creatinine clearance studies in the pig are complicated by difficulties with catheterisation, infection, accurate collection and active creatinine renal tubular reabsorption. We compared a single injection, 99mTc-DTPA elimination method with creatinine clearance. Nineteen pairs of GFR estimations were performed in 10 pigs: 7 in normal pigs and 12 following bile duct ligation and/or nephrectomy. Red cell and plasma protein binding of the isotope and its hepatobiliary excretion was assessed. Absolute and weight normalised endogenous creatinine clearances correlated significantly with 99mTc-DTPA elimination. 99mTc-DTPA red cell binding and hepatobiliary excretion were negligible. Thus, 99mTc-DTPA elimination is a valid indicator of changes in renal function in grouped porcine studies, particularly in the biliary obstruction model. However, isotope plasma protein binding was high in the 2 normal pigs assessed. Individual accuracy would be improved by routine protein binding correction, unless consistently low for a particular preparation.

Animals↗

Partial hepatectomy and liver regeneration in pigs--the response to different resection sizes.

Liver regeneration has been extensively studied in the rat and dog models but pigs have seldom been used. They resemble man closely in their omnivorous diet and their gastroenterological and endocrinological responses. This paper describes techniques of 15, 50, 65, and 70% partial hepatectomy in the pig. Thymidine kinase activity and mitotic index were used as indices of liver regeneration. The timing and events of the regenerative response in the pig compared favorably with other animal models and the maximum regenerative response occurred on the third postoperative day, irrespective of the size of the partial hepatectomy. The 15% partial hepatectomy, which shows a minimal response to resection, provides a suitable "primed" model for the study of stimulatory substances.

Animals↗

The effect of hepatic devascularisation in the pig upon the energy charge and ketone ratio.

This study describes the effects upon various functions of the porcine liver, especially the energy charge, after ligation of the hepatic artery or diversion of portal venous blood either with or without revascularisation by arterial or vena caval blood. Energy charge was significantly reduced for up to 2 days after arterial ligation but by 7 days was showing a return towards normal. Levels of adenosine triphosphate were affected most. The ketone body ratio was well maintained. A sharp elevation in levels of aspartate aminotransferase was noted at 2 days but had returned towards normal by 7 days while the prothrombin index and plasma fibrinogen tended to fall. There were inconsistent changes after portal diversion. These data indicate that the hepatic arterial, rather than portal venous inflow is important in the maintenance of porcine hepatic energy charge. This fact has physiological implications, and there is also an important application in the field of liver transplantation, where it may be that the ischaemic liver should be rearterialised first rather than after revascularisation with portal venous blood.

Adenosine Diphosphate↗

Description, validation, and performance characteristics of a new computer-automated sperm motility analysis system.

A computer-automated sperm motility assay (CASMA) system has been developed that provides a rapid and accurate analysis of multiple sperm movement parameters and a new measure of linearity, the linear deviation angle. CASMA provides objective, unbiased sampling and accurate quantitation of the movement characteristics of 200 sperm cells in 20 min. It consists of a microscope-mounted video camera, a high-resolution video disk recorder, a video digitizer/memory board mounted in an IBM 9000 microcomputer, and newly developed software. After manual recording, at 60 frames/s, of the video sequences (takes) of sperm suspensions, each take is automatically played back frame by frame, digitized, and stored in video memory. The software searches each frame, recognizes sperm cells, randomly selects a preset number for analysis, and traces each cell through the sequence to generate sperm "tracks" that are then stored in disk memory. This process is repeated for each take. Analysis of the stored tracks of each take yields the mean +/- SEM of the standard sperm motility parameters: percent motile (%M), curvilinear velocity (VC), net velocity (Vn), position-averaged velocity (Va), linear index (Vn/Va), progressiveness ration (Vn/Vc), and curvilinear progressiveness ratio (Va/Vc). Additionally, CASMA allows measurement of the linear deviation angle, a more direct measure of the linearity of sperm movement. For statistical comparisons, multiple takes can be considered either as replicates or separate experimental determinations. Finally, for more detailed analysis, each individually stored track, with its associated parameters, or histogram distributions of all sperm for each parameter can be displayed and printed. The performance of CASMA was evaluated by comparison of CASMA-determined movement parameters with manually determined values derived from the same sperm cells in the same video sequence and by comparison with published values determined using microcinematographic techniques. In each case, the CASMA values were essentially identical to those determined by manual measurements. Finally, CASMA accurately quantitates the linearity of sperm movement, a characteristic previously determined only by much more time-consuming methods. CASMA is a rapid and accurate system for measuring washed bull sperm motility and has reliably analyzed monkey and elephant sperm. The system has the potential to quantitate motility equally well with sperm from any species that have similar sperm head size.

Animals↗

Hepatic stimulator substance in extracts from regenerating porcine liver. Basic physiochemical properties.

Previous studies in rats and dogs have implicated the liver as the source of some of the factors which are responsible for its regeneration. In the present study extracts from regenerating and normal livers were infused into the portal vein of pigs after a 15% partial hepatectomy. Thymidine kinase activity was measured on the 3rd and 4th days as an index of liver regeneration. An intraportal infusion of extracts from regenerating, but not normal, livers resulted in an increased regenerative response. The response was dose-related. The stimulator substance was stable when stored at -20 degrees C and could be precipitated by absolute ethanol.

Animals↗

Aluminium excretion by the distal tubule of the pig kidney.

The renal tubular handling of aluminium was investigated, using the stop-flow method, in 8 pigs (2 controls, 2 'dose range', and 4 experimental). Aluminium was measured by graphite furnace atomic absorption spectroscopy. In 11 stop-flow studies in the 4 experimental pigs, intratubular aluminium concentrations, corrected for water reabsorption, peaked in the distal nephron. Interrupted stop-flow revealed that aluminium was excreted into the tubule at this site. The aluminium excretion site was situated at or close to the sites of maximal calcium and sodium reabsorption. Aluminium excretion occurs in the distal tubule of the pig kidney.

Aluminum↗

A porcine model for the study of liver regeneration.

A technique of 65% partial hepatectomy in the pig is described. Thymidine kinase activity and mitotic index were used as indices of liver regeneration. Thymidine kinase activity increased from a baseline value of 1526 +/- 256 to a maximum of 23992 +/- 4966 dpm/mg protein on the third day after partial hepatectomy. The mitotic index also increased from 0-13.3 +/- 1.66 on the third postoperative day. The indices of regeneration remained unchanged after sham operation.

Animals↗

Early diagnosis and management of renovascular hypertension.

Renovascular hypertension is more common in hypertensive children than in hypertensive adults, and renal artery stenosis is second only to coarctation of the thoracic aorta as a cause of surgically correctable hypertension. Three infants presented with uncontrollable hypertension secondary to renal artery thrombosis due to umbilical artery catheterization for respiratory distress in the neonatal period. They all responded to nephrectomy. A fourth infant had stenosis of a polar vessel secondary to umbilical artery catheterization and was cured by partial nephrectomy. Two infants with renal artery stenosis secondary to fibromuscular dysplasia benefited from revascularization and, at last follow-up, were normotensive and off all blood pressure medication. Ultrasonography, isotope scanning, angiography and selective renal vein renin assays should be used to identify patients with surgically correctable lesions. The use of fine suture material and microvascular surgical techniques, including ex vivo revascularization and autotransplantation, can salvage renal parenchyma and relieve hypertension. Infants with less than 10 percent renal function on the involved side should have a nephrectomy. The infant with an umbilical arterial catheterization line needs blood pressure monitoring and aggressive evaluation and treatment of persistent hypertension.

Fibromuscular Dysplasia↗

The effect of prostaglandins, branched-chain amino acids and other drugs on the outcome of experimental acute porcine hepatic failure.

Prostaglandins, N-acetyl-cysteine, cholestyramine and essential phospholipids have all been shown to protect experimental animals from severe hepatic damage in various models when used prophylactically. Silibinin has been used in the treatment of Amanita phalloides poisoning. Branched-chain amino acids have been recommended in acute hepatic failure. We have used all these forms of therapy at the time of initiation of hepatic failure in a reliable pig model. Of the above, only prostaglandins have been shown to reverse the effects of the hepatic insult in terms of prolonged survival and histological changes. Although conventional liver function tests and plasma amino acids in prostaglandin-treated animals are not improved, cerebrospinal fluid amino acids remain normal, in contrast to the other groups of untreated and treated hepatic failure animals.

Acetylcysteine↗

Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids.

To examine the effects of anabolic steroid use on glucose homeostasis, we determined oral glucose tolerance and serum insulin response to glucose in 15 male powerlifters, 6 obese men, and 10 sedentary nonobese men. Eight of the powerlifters had self-administered large doses (200 mg/day) of anabolic steroids for periods of up to 7 yr, whereas 7 had never used anabolic steroids. Powerlifters who ingested anabolic steroids had diminished glucose tolerance compared to the nonsteroid-using group, despite having substantially higher postglucose serum insulin concentrations. Postglucose insulin responses were also higher in steroid users than in the sedentary nonobese and sedentary obese reference groups. These results indicate that powerlifters who ingest anabolic steroids have diminished glucose tolerance, which is likely to be secondary to insulin resistance.

Adult↗

Sustained feeding or fasting affects levels of glucagon (IRG) in porcine plasma, gut and pancreas.

Arterial glucagon levels are elevated in fed pancreatectomised pigs and the source was sought by measuring the hormone in arterial, portal, hepatic and renal venous blood, and in gut tissues. Pigs which were starved for 48 hours (basal) were compared with sham operated or pancreatectomised pigs which were fed or starved for 7 days post operatively. Feeding of sham operated pigs caused a uniform increase in IRG 3485, while starvation resulted in a decreased portal IRG 7000. Pancreatectomy was associated with a uniform decrease in portal IRG 3485 and increase of IRG 7000 regardless of nutritional status. Hepatic and renal extraction of 23-26% was noted in fed animals (IRG 3485 in sham operated; IRG 7000 in pancreatectomised). In all starved pigs, hepatic and renal extraction were reduced to zero. The gastric and caecal mucosa and the pancreas contained most of IRG 3485. Gastric and caecal levels were increased after feeding of either group of animals, while fasting caused a marked increase in pancreatic IRG 3485 and a decrease in ileal IRG 7000. These studies demonstrate a direct effect of sustained nutritional status upon the distribution of glucagon in plasma and gastro intestinal tissues.

Animals↗