Women in medicine. A literature review--1985-1996.
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Career Choice↗
Biomedical subjects
R Hickman
Publications and source records attributed to R Hickman.
Early effects of total hepatectomy on haemodynamic state and organ uptake of catecholamines in the pig.
In a previous study, we showed that plasma concentrations of catecholamines were increased during the anhepatic phase in pigs. In this study, we investigated if a constant depth of anaesthesia would prevent these changes and, if not, if the changes were caused by impaired extraction of catecholamines. We measured arterial and venous pressures, heart rate and cardiac output in 10 anaesthetized pigs. Hepatic arterial and portal venous flows were measured. Blood for measurement of catecholamines was sampled from carotid and pulmonary arteries and portal, hepatic and renal veins. After a 2-h observation period, the liver was removed and the circulation reconstituted. Measurements were made and samples obtained for another 2 h. Catecholamine concentrations increased 2-10-fold after hepatectomy. Before hepatectomy, noradrenaline was extracted by the lung (mean extraction ratio 23 (SEM 8)%) and the liver (30 (11)%); after hepatectomy, there was extraction by the kidney (24 (12)%) but extraction by the lung (29 (8)%) was unchanged. Before hepatectomy, adrenaline was extracted predominantly by the kidney (73 (5)%) and the liver (70 (6)%), with minimal extraction by the lung; after hepatectomy, extraction by the lung increased (25 (4)%) and decreased slightly in the kidney (56 (6)%). While mean arterial pressure did not change, heart rate increased by approximately 50% and cardiac index declined (ns) within 2 h after hepatectomy. There was a sharp increase in pulmonary vascular resistance after removal of the liver and changes correlated with increases in arterial plasma concentrations of catecholamines.
Anesthesia, General↗
Hepatic blood flow during reduced liver grafting in pigs. A comparison of controls and recipients of intact allografts.
Intraoperative changes in portal venous and hepatic arterial flow were compared in porcine recipients of reduced liver grafts with recipients of intact grafts and sham-operated controls. Control animals showed no significant changes in hepatic blood flow (measured with perivascular ultrasonic cuffs), heart rate, mean arterial pressure, cardiac output, acid/base balance, plasma sodium, potassium, glucose, or catecholamines. Recipients of intact or reduced grafts showed hypotension, reduced cardiac output, tachycardia, and increased systemic vascular resistance during the anhepatic phase, which lasted approximately 30 min. These changes returned to normal in recipients of intact grafts but in recipients of reduced grafts, levels returned only to 50-60% of baseline. After intact grafting, total liver blood flow and the portal and arterial components returned to baseline within 2 hr of revascularization, but after reduced grafting, hepatic arterial flow values remained depressed to 50-60% of baseline. Plasma epinephrine and norepinephrine were unaltered during control operation but increased 4- to 20-fold in recipients of all grafts. These returned towards baseline in all except recipients of reduced grafts, in which norepinephrine levels remained significantly elevated for the 4 hr of postoperative study. These data highlight persistent elevation of plasma norepinephrine after reduced liver grafting, which may have contributed to the diminished hepatic arterial flow. These results need to be confirmed in adult recipients of split liver grafts in whom grafts are comparatively small. In such patients receiving donor livers which have undergone prolonged storage, the effects of increased plasma norepinephrine levels upon donor agonal arterial spasm may be significant.
Animals↗
Substance P level is increased in the cholesterol induced anaphylactoid reaction in the pig.
The role of substance P (SP) in cholesterol-induced anaphylactoid reaction was investigated in 13 Landrace pigs. Pigs were anesthetized with sodium thiopental and ventilation was controlled with 70% nitrous oxide in oxygen. A Swan-Ganz catheter and a carotid arterial line were placed to monitor the hemodynamic data. Group 1 pigs (control group, n = 5) each received 20 ml of intravenous (IV) colloid infusion solution (Haemaccel) and group 2 pigs (cholesterol group, n = 8) each received an IV injection of pure cholesterol emulsion (12 mg/kg) in 20 ml of Haemaccel. Blood samples for SP and histamine (H) levels were taken just before and for 10 min following the placebo, Haemaccel, and cholesterol injections. Urine samples were also collected just before and at 60 min following the injections for methyl histamine (MH) levels. Group 2 pigs (cholesterol) developed an anaphylactoid reaction as indicated by marked and significant hemodynamic changes. None of the group 1 (placebo) pigs developed an anaphylactoid reaction. Significant increases in blood SP and H levels (P < 0.05), and urine MH levels (P < 0.05) were seen in cholesterol-treated pigs (group 2), whereas no significant changes were seen in control pigs (group 1). Our results suggest that SP is involved in the cholesterol-induced anaphylactoid reaction in pigs.
Anaphylaxis↗
Transposition of the antropylorus for anal incontinence--an experimental model in the pig.
An experimental model in the pig rendered incontinent of feces was developed to assess the sphincteric activity of the transposed antropylorus. In the control group, normal defecation was studied clinically, radiologically, and manometrically. Nineteen 7- to 10-week-old pigs were rendered incontinent by resection of 20 cm of colon and rectum to below the dentate line. The antropylorus was prepared on its own blood supply and transposed to the anus, initially with a colostomy, which was closed 15 to 21 days later. Clinically these pigs passed semisolid stool in a piecemeal fashion. Contrast defecography showed hold-up at the pylorus, reflux of contrast into the colon, with pyloric contraction independent of antral stimulation. Manometry showed pyloric contraction with rise in antral pressure and independence. The authors conclude that transposition of an antropyloric segment to the anus provides a sphincter-like mechanism and could have application in fecal incontinence.
Animals↗
Haemostatic and immunological sequelae of portacaval shunt in rats.
We have evaluated the link between haemostatic abnormalities and immune dysfunction in liver disease by evaluating parameters of cellular and humoral immunity in conjunction with coagulation profiles in rats following portacaval anastomosis, induction of portal hypertension by portal vein stenosis or by sham surgical procedures. Twelve weeks following surgery, portacaval shunted rats were markedly anaemic (8.9 +/- 0.6 g/dl; controls 12.3 +/- 1.4 g/dl, p < 0.05), had low plasma fibrinogen levels (0.6 +/- 0.3 g/l, controls 2.5 +/- 0.2 g/l p < 0.05) and markedly elevated fibrin(ogen) degradation products (FDP) titres (1/40-1/80; controls < 1/10. p < 0.05). Portal vein stenosed rats were less anaemic (11.5 +/- 0.8 g/dl), had near normal fibrinogen levels (2.1 +/- 0.3 g/l) but elevated FDP levels (1/40-1/80). Both portacaval shunted and portal vein stenosed rats had elevated serum IgG levels (35.1 +/- 14.1 g/l; 29.2 +/- 13.9 g/l respectively; control values 20 +/- 5.9 g/l p < 0.05 for comparison with both experimental groups). Intrinsic lymphocyte proliferation to T and B cell mitogens was markedly depressed in the portacaval anastamosed rats when compared to controls. Serum factors inhibitory to control lymphocyte proliferation were noted in the shunted rats. Phagocytosis of complement and immunoglobulin sensitised sheep RBC by Kupffer cells purified from rats that had undergone portacaval shunting was markedly reduced (p < 0.05). The increased degree of phagocytosis following exposure to LPS-endotoxin (50 micrograms/ml) was proportionate in degree to the control group. Spontaneous release of bioactive lymphocyte activating factors (IL-1 and IL-6) by purified rat sinusoidal cell populations was decreased in the portacaval shunted group, and decreased still further following stimulation with LPS (50 micrograms/ml) in vitro. The observation that many of the haemostatic and immunological abnormalities associated with chronic liver disease are present in rats with surgically created portacaval shunts or with induced portal hypertension, lends credence to the hypothesis that shunting of portal blood is, at least in part, responsible for many of the systemic manifestations associated with chronic liver disease.
Animals↗
The influence of flow and hematocrit on the laser Doppler flux signal from the surface of the perfused pig liver.
OBJECTIVE: We tested the hypothesis that the measurement volume of the laser Doppler flowmeter (LDF) is too small to provide reliable quantitative estimates of total liver blood flow of large mammals, such as the pig. METHODS: In a perfused pig liver, the influence of changing (i) hepatic arterial (HA) and portal venous flows individually (n = 9), (ii) HA flow at fixed portal venous flow (50%, 70%, and 100% expected total liver blood flow), and (iii) hematocrit (0-30%) at fixed total liver blood flow on LDF flux was tested (n = 8). RESULTS: Linearity of LDF with hepatic arterial flow and portal venous flow was confirmed; however, the slope of the regression lines was higher for hepatic artery [1.92 +/- 0.60 (SD)] than portal vein perfused livers (0.66 +/- 0.34; P < 0.001). With portal venous flow at 50% and 70% total liver blood flow, changing hepatic arterial flow produced linear LDF versus flow responses, but at 100% total liver blood flow, linearity was achieved in only 6/9 livers. The coefficient of variation for the slopes of regression lines was always > 30%. At constant total liver blood flow (100 ml/min per 100 g), LDF response decreased linearly by a factor of about 2 on changing the hematocrit from 30% to 5% and markedly fell as the hematocrit was further decreased to zero. CONCLUSIONS: These results suggest that (i) the LDF flux signal from the liver surface provides a poor measure of hepatic microcirculatory blood flow during changes in total liver blood flow as the LDF responds with about three times greater sensitivity to changes in hepatic arterial than in portal venous flow, and (ii) when hematocrit is falling, LDF may underestimate hepatic perfusion to a significant extent. In addition, due to high measurement variability, the LDF flux signal cannot be quantified in absolute perfusion units.
Analysis of Variance↗
Regeneration after in situ flushing of partially hepatectomised rat livers.
The effect of various components of the transplant procedure upon the regenerative process in reduced liver grafts is not known. In this study, partially hepatectomised rat liver remnants were flushed with 5 ml of either Ringer's lactate, Euro Collins solution or University of Wisconsin solution at 4 degrees C and then 5 ml Ringer's lactate at 4 degrees C. After partial hepatectomy alone, the peak increase in thymidine kinase was measured at 24 hours (36,021 +/- 8,060 disintegrations per minute per milligram protein; the mitotic index was 25 +/- 7). In all the groups in which the remnant was flushed, peak thymidine kinase and mitotic index were measured at 48 hours. The pattern of ornithine decarboxylase activity was disorganised in all groups. Flushing of the liver remnant therefore delays the regenerative response by 24 hours. In large animals, including humans, regeneration appears to commence within the first 5 days after resection. A comparable delay doubling this time might coincide with the onset of rejection and further compromise liver function.
Animals↗
Investigating the reliability and validity of the infrared tympanic thermometer: a learning experience.
This series of articles to date has discussed points that readers should be looking for when reading and critiquing a researcher article. This article presents a brief report of a research project investigating the reliability and validity of the infrared tympanic thermometer (ITT) in afebrile subjects. Using four subjects and 40 temperature diads, the ability of the ITT to predict the subjects' temperatures obtained with a mercury thermometer was very poor (regression coefficient = .39). Test-retest reliability using the same data set resulted in an equally poor correlation coefficient (r = .19). A critique of the methodology of the study is provided as a learning experience.
Humans↗
The effect of administration of FK506 on delayed regeneration in flushed partially hepatectomized livers.
It has been shown previously that liver regeneration after partial hepatectomy in rats is delayed if the liver is subjected to either concurrent ischaemia, flushing with cold solution, or grafting. We have shown recently that treatment with CsA preoperatively overcomes the suppressive effect of flushing and returns the regenerative response to a normal time scale. The present study was designed to investigate whether administration of FK506 would also return the observed delayed regenerative response to normal. Long-Evans rats weighing 250-350 g were subjected to standard 68% partial hepatectomy. Group 1 had no further treatment; in group 2, the liver remnant was flushed with 10 ml cold (4 degrees C) Ringers lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by intramuscular injection for 3 days before the partial hepatectomy and flushing as in group 2; a final dose was given after completion of the procedures. Animals were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and blood samples were taken for measurement of plasma aspartate amino-transferase. Liver biopsies were analyzed for measurement of thymidine kinase and ornithine decarboxylase activity and for counting of mitotic figures. While the highest recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed to 48 hr in both group 2 and 3 and counts remained high up to 96 hr in group 3. Mitotic indices were only significantly elevated (compared with group 1 at 96 hr), while ornithine decarboxylase activity did not correlate with these changes being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at 24 hr. Plasma aspartate aminotransferase was also significantly higher in group 3. It is concluded that the administration of FK506 preoperatively to rats subjected to partial hepatectomy and flushing did not restore the delayed regenerative response to normal but enhanced the response (as measured by thymidine kinase but not by mitotic indices) which commenced at 48 hr and was still present at 96 hr.
Animals↗
Cytoskeletal actin: the influence of major burns on neutrophil structure and function.
It has been noted that major trauma and burns patients who survive beyond 48 h most frequently succumb to sepsis and multiple organ failure. Furthermore, such patients are usually markedly hypermetabolic and in negative nitrogen balance at the time of their demise. Along with many other systemic and immune dysfunctions, the polymorphonuclear white blood cells in this setting become functionally impaired. Given that the motile white blood cells contain significant proportions of the contractile protein, actin, we speculated that the leucocyte dysfunction might in part be related to the overall systemic catabolism of actin stores. Accordingly, this hypothesis was explored by comparing the functions and cytoskeletal structure of neutrophilic leucocytes from normal control adults and victims of fresh, major thermal injuries. On days 1 and 7 after a burn of > 25 per cent of total body surface area, peripheral blood was drawn from 10 patients (mean age 33 years, mean burn area 44.2 per cent), and seven unburned controls (mean age 35.2 years). Neutrophils isolated from these specimens were tested for stimulated chemotactic rate, efficacy of intracellular killing as determined by superoxide production rate, and the levels of soluble and insoluble intracellular actin. In addition, both light microscopy and scanning electron microscopy were used to visualize the actin cytoskeleton. The results indicated that both chemotactic rate (12 mu/min vs. 38 mu/min--P < 0.05) and superoxide production rate (9 vs 43 mumol/ml10E6 cells--P < 0.05), were significantly reduced in the burn patients by day 7.(ABSTRACT TRUNCATED AT 250 WORDS)
Actins↗
Alcohol pretreatment alters the metabolic pattern and accelerates cocaine metabolism in pigs.
We investigated whether alcohol pretreatment would affect the disposition and metabolic pattern of intravenously (i.v.) administered cocaine in pigs. Six pigs (Group A) received alcohol (1 g/kg/day) and six pigs (control; Group D) received an equal volume of isocaloric dextrose 44% in water for 10 days via an intragastric tube. On day 11, arterial samples were taken for five hours following an intravenous administration of cocaine hydrochloride (4 mg/kg). Plasma concentrations of cocaine and its major metabolites were analyzed by HPLC method. Significant decrease in plasma half-life (10 +/- 1.2 vs. 18.7 +/- 1.4 min), and significant increases in apparent volume of distribution (73 +/- 6 vs. 51 +/- 31) and clearance (5.37 +/- 0.6 vs. 1.82 +/- 0.1 l/min) were seen in alcohol pretreated pigs as compared with control pigs (P < 0.05). Significant increases in plasma concentrations of benzoylecgonine (P < 0.05), and insignificant differences in ecgonine methyl ester and norcocaine levels were seen between the two groups. Neither ecgonine nor cocaethylene was detected in the blood samples. Our data show that alcohol administration for ten days accelerated the elimination of i.v. administered cocaine and altered its metabolic pattern in pigs.
Animals↗
The regenerative response in intact young livers grafted into different sized recipient pigs.
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Animals↗
Lidocaine extraction by the in vivo and isolated perfused pig liver.
Hepatic lidocaine elimination is increasingly being used to assess hepatic function. Although the isolated liver is extensively used as a model of in vivo function, it is necessary to determine whether this is a suitable model for in vivo lidocaine elimination. Fourteen male pigs (22-25 kg) were divided into two groups. Seven were anesthetized, and catheters and perivascular flow probes placed for transhepatic sampling and hepatic arterial and portal venous flow measurement. Sampling was performed at hourly intervals to determine hepatic function and plasma composition. Hepatic lidocaine elimination was determined during the second hour of a lidocaine infusion (1.41 mg.kg-1.min-1 for 10 min, then 0.165 m.kg-1.min-1), during which time the mean hepatic blood flow rates, plasma acid base status and body temperature were measured so that these could be emulated in the isolated perfused liver experiments. Seven male pigs were then anesthetized and the liver resected and cannulated for isolated liver perfusion. Hepatic arterial and portal venous blood flow and perfusate temperature were set to the mean in vivo values, and hepatic function and perfusate composition assessed at corresponding times. Hepatic lidocaine elimination was determined at a similar hepatic inflow whole blood concentration (+/- 5 micrograms.ml-1) to that in vivo over the second hour of lidocaine administration (40 mg bolus, then 2.8 mg.min-1). Lidocaine extraction ratio in vivo (0.61 +/- 0.04) [mean +/- SEM] and ex vivo (0.63 +/- 0.02) was similar, as was hepatic blood clearance (381 +/- 70 vs 363 +/- 16 ml.min-1) and hepatic blood intrinsic clearance (1132 +/- 280 vs 1069 +/- 109 ml.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenine Nucleotides↗
Changes in glucoregulatory and thyroid hormones after reduced liver grafts in pigs.
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Animals↗
The effect of a tumour necrosis factor antibody on the regenerative response after partial hepatectomy in rats.
In this study we investigated the effect of tumour necrosis factor (TNF) on the regenerative response after partial hepatectomy. Adult male rats were injected intravenously with an antibody to TNF immediately after partial hepatectomy. Animals were sacrificed at 0, 24, 48, 72 and 96 h postoperatively. Hepatic thymidine kinase (TK) activity, liver weight to body weight (LW/BW) ratio, and mitotic index (MI) were used as indices of hepatic regeneration. The rats treated with TNF-Ab had significantly lower levels of TK activity in the liver at 24 h postoperatively compared to the saline treated animals. Furthermore the peak hepatic TK activity was delayed to 48 h in the rats treated with TNF-Ab. The mitotic indices and LW/BW ratios in the TNF-Ab- and saline-treated animals were similar. These data suggest that TNF potentiates the regenerative response after partial hepatectomy.
Animals↗
Does liver transplantation in the rat cause a regenerative response. The effect of arterialisation of the graft.
This study was conducted to determine the pattern of early regenerative response to orthotopic intact liver transplantation in the rat and to investigate whether the response differed in grafts with or without revascularisation of the arterial bed. Outbred male Long Evans (LE-LE allogeneic, non rejector) rats weighing 300-350g were subjected to orthotopic intact liver allograft using a "sleeve" anastomosis for the hepatic artery. Total warm ischaemia ranged from 19 to 34 minutes and no storage was employed. Comparison was made with a group of control rats which were subjected to 25 minutes total inflow occlusion and regeneration was measured with tissue thymidine kinase (TK) and mitotic figures. Samples were taken at 1, 2, 4, 7, 10 and 20 days post-operatively. Plasma aspartate aminotransferase (AAT) and light microscopy were used to evaluate hepatocyte necrosis. There was a brief sharp increase in TK and AAT in the first 24 hours after sham operation but no appearance of mitotic figures. A similar but more prolonged increase in TK occurred in the arterialized transplant group with the highest levels recorded on day 4. The level remained significantly elevated above pre-operative until 10 days and declined within 20 days. Mitotic figures appeared at 2 days, reached significance at 7 and 10 days and had disappeared by 20 days. The pattern of changes was accentuated in animals in which the artery was not reanastomosed and the increases in TK and AAT were still significant at 20 days. Whilst similar degrees of peri-portal cellular infiltrate occurred in both groups of rats, bile duct proliferation was most obvious in non-arterialized animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Anastomosis, Surgical↗
The effect of hepatectomy and plasma cholinesterase inhibition on cocaine metabolism and cardiovascular responses in pigs.
To determine the effects of total hepatectomy and inhibition of plasma cholinesterase activity on cocaine metabolism, we measured plasma concentrations of cocaine and its three major metabolites, benzoylecgonine, ecgonine methyl ester, and norcocaine, by high-performance liquid chromatography in three groups of male pigs. Pigs were anesthetized with sodium thiopental and lungs were ventilated with nitrous oxide in oxygen. A right carotid arterial cannula and an internal jugular venous catheter were then inserted for the administration of cocaine and for blood sampling. A Swan-Ganz catheter was inserted through the right internal jugular vein. Group 1 pigs underwent sham operation; group 2 and 3 pigs underwent hepatectomy and portocaval shunt. In addition, group 3 pigs were treated with tetraisopropyl pyrophosphoramide, a specific plasma cholinesterase inhibitor. After this preparation, pigs were given 4 mg/kg cocaine intravenously over 2 minutes. After cocaine injection, 4 ml blood was collected into heparinized test tubes containing 2.5% sodium fluoride for determination of cocaine and its metabolites at 2, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. We also measured hemodynamic responses after cocaine administration, including heart rate and rhythm, cardiac output, and arterial blood pressure. Data were analyzed by analysis of variance. Blood levels of cocaine and its metabolites were significantly different among the three groups (p < 0.05 by analysis of variance). Our results show that total hepatectomy was associated with a marked slowing of cocaine metabolism, absence of norcocaine, and increased benzoylecgonine levels when compared with the baseline values in the control pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗