Stress and the immune system: preliminary observations in rheumatoid arthritis using an in vivo marker of immune activity

This study measured volumetric liver blood flow and galactose clearance concurrently during orthotopic liver transplant in human subjects. Ultrasound transit time flowmeters measured hepatic artery and portal vein flow 1-3 h after reperfusion. Galactose (100 mg/min) was infused over 45-60 min to steady state for calculation of clearance. Mean +/- S.D. total volumetric flow was 1966 +/- 831 ml/min with portal flow contributing 86%. Mean galactose clearance was 1988 +/- 641 ml/min. There was a significant correlation (p < 0.05, r = 0.61) between volumetric total liver blood flow and galactose clearance. The data show that: (i) the newly transplanted liver is capable of metabolizing galactose within 1-3 h of reperfusion; and (ii) liver blood flow is high in the newly implanted liver. The clinical importance of this observation is that there is increased clearance of high first pass substances by the transplanted liver which may be of importance in patient management.     

Membrane association of sucrose synthase: changes during the graviresponse and possible control by protein phosphorylation

Mean manganese superoxide dismutase (Mn-SOD) concentrations in the serum of patients suffering from alcohol dependence is almost twice as high as in serum of non-dependent controls. In order to investigate the time course of this parameter during abstinence, we determined it at different time points. Patients had mean Mn-SOD serum concentrations (+/-S.D.) of 150.4 +/- 76.3, 121.1 +/- 40.7, 94.6 +/- 37.8 micrograms/ml at 1, 10 and 40 days after abstinence compared to 76.3 +/- 16.9 micrograms/ml as mean Mn-SOD value in the control group. Although the Mn-SOD concentration tended to normalise during abstinence, the differences between index and control group remained significant up to the last measurement at day 40.     

CT with different doses of the hepatocyte-specific contrast medium FP 736-03. Evaluation in a nude-rat model of experimental metastases

PURPOSE: To study the dose-response relationship in FP 736-03 (48 mg I/ml), hepatocyte-specific contrast medium for CT of the liver. MATERIAL AND METHODS: A nude-rat model of experimental hepatic metastases was used. CT of the liver was performed before and after i.v. injection of FP 736-03 at 4 different doses: 0.25, 0.5, 1.0 and 2.0 ml/kg b.w. Attenuation in the normal liver parenchyma and in the metastases was measured and plotted as a function of time. RESULTS: The enhancement of the normal liver parenchyma increased in the dose range studied. No increase was found in the metastases: the attenuation here remained constant during the observation period. The maximum enhancement values at doses of 0.25, 0.5, 1.0 and 2.0 ml/kg b.w. were (mean +/- SD) 13.5 +/- 2.7, 30.1 +/- 4.2, 33.2 +/- 4.5 and 59.7 +/- 13.1 HU respectively.     

Effect of stimulation of hepatic nerves on hepatic O2 uptake and blood flow

Raising the hepatic venous pressure experimentally duplicates the type of hepatic congestion seen in many clinical situations including congestive heart failure. Venous pressure was controlled using a hepatic venous long circuit preparation and was raised by 6 cm blood (4.7 mm Hg) or 10 cm (7.8 mm Hg). Total splanchnic blood flow and oxygen uptake were reduced by these maneuvers but hepatic arterial flow was not altered nor was hepatic oxygen uptake. Blood flow in the portal vein decreased to 65 +/- 12% of control and gut oxygen uptake decreased to 60 +/- 14% of control. The data confirm that raised hepatic venous pressure does not produce hepatic edema in spite of massive prolonged fluid filtration across the liver into the peritoneum. In spite of a reduced (to 84 +/- 3% of control) hepatic oxygen delivery, the liver can maintain oxygen uptake (99 +/- 7% of control) by increasing oxygen extraction to appropriate levels. The hepatic artery in these cats were capable of myogenic vasoconstriction in response to altered arterial pressure, but in response to raised venous pressure no tendency for constriction was seen. This is in marked contrast to the vasoconstriction seen in isolated perfused livers where portal blood flow is held constant during the raised venous pressure.     

Effect of hypohydration on gastric emptying and intestinal absorption during exercise

Dehydration and hyperthermia may impair gastric emptying (GE) during exercise; the effect of these alterations on intestinal water flux (WF) is unknown. Thus the purpose of this study was to determine the effect of hypohydration ( approximately 2.7% body weight) on GE and WF of a water placebo (WP) during cycling exercise (85 min, 65% maximal oxygen uptake) in a cool environment (22 degrees C) and to also compare GE and WF of three carbohydrate-electrolyte solutions (CES) while the subjects were hypohydrated. GE and WF were determined simultaneously by a nasogastric tube placed in the gastric antrum and via a multilumen tube that spanned the duodenum and the first 25 cm of jejunum. Hypohydration was attained 12-16 h before experiments by low-intensity exercise in a hot (45 degrees C), humid (relative humidity 50%) environment. Seven healthy subjects (age 26.7 +/- 1.7 yr, maximal oxygen uptake 55.9 +/- 8.2 ml . kg-1 . min-1) ingested either WP or a 6% (330 mosmol), 8% (400 mosmol), or a 9% (590 mosmol) CES the morning following hypohydration. For comparison, subjects ingested WP after a euhydration protocol. Solutions ( approximately 2.0 liters total) were ingested as a large bolus (4.6 ml/kg body wt) 5 min before exercise and as small serial feedings (2.3 ml/kg body wt) every 10 min of exercise. Average GE rates were not different among conditions (P > 0.05). Mean (+/-SE) values for WF were also similar (P > 0.05) for the euhydration (15.3 +/- 1.7 ml . cm-1 . h-1) and hypohydration (18.3 +/- 2.6 ml . cm-1 . h-1) experiments. During exercise after hypohydration, water absorption was greater (P < 0.05) with ingestion of WP (18.3 +/- 2. 6) and the 6% CES (16.5 +/- 3.7), compared with the 8% CES (6.9 +/- 1.5) and the 9% CES (1.8 +/- 1.7). Mean values for final core temperature (38.6 +/- 0.1 degrees C), heart rate (152 +/- 1 beats/min), and change in plasma volume (-5.7 +/- 0.7%) were similar among experimental trials. We conclude that 1) hypohydration to approximately 3% body weight does not impair GE or fluid absorption during moderate exercise when ingesting WP, and 2) hyperosmolality (>400 mosmol) reduced WF in the proximal intestine.     

A simple radioimmunoassay for plasma cortisol: comparison with the fluorimetric method of determination

A quick and simple method for the radioimmunoassay of plasma cortisol is described. The mean morning plasma cortisol concentration in 43 normal subjects was 9.8 +/- 3.1 (S.D.) microgram/100 ml with a range of 5.0-19.5 microgram/100 ml. Mean midnight concentration in 24 normal subjects was 4.3 +/- 2.3 (S.D.) microgram/100 ml with a range of 1.4-9.6 microgram/100 ml. When compared with the fluorimetric method the mean results by radioimmunoassay of 154 routine specimens were 23% lower. In samples from unstimulated patients, regression analysis of results obtained by the two methods gave a correlation coefficient (r) of 0.93, regression line slope of 1.1, and intercept of 1.4 microgram. Mean radioimmunoassay results were 15% lower. When plasma cortisol concentration was above the normal range (greater than 30 microgram/100 ml) the regression line slope was 0.87, the intercept 17.9 microgram, r = 0.87 and mean radio immunoassay results were 37% lower. Plasma cortisol concentration in patients after insulin or Synacthen stimulation exhibited similar responses when measured by either method. Plasma cortisol concentration in normal subjects given metyrapone was lower when measured by radioimmunoassay (mean +/- S.D. = 8.7 +/- 2.7 microgram/100 ml) than when measured by fluorimetry (18.5 +/- 10.8 microgram/100 ml). The diagnostic usefulness of the two methods, ease of assay, and costs are compared.     

Gas exchange, blood acid-base balance and mechanical muscle efficiency during incremental levels of exertion in young healthy individuals

In this study we have evaluated the changes in gas exchange variables, blood acid-base balance and the mechanical efficiency of muscle in healthy young men during an incremental exercise test. Twenty-six healthy men: age 22.1 +/- 1.4 (mean +/- SD) years, body mass 73.6 +/- 7.4 kg, height 179 +/- 8 cm, were subjects in this study. The subjects performed an incremental exercise test on a cycloergometer at a pedalling rate of 70 rev.min-1. The exercise test started at a power output of 30 W, followed by an increase of power output by 30 W every 3 minutes. Gas exchange variables were measured continuously (breath by breath). Antecubital blood samples for acid-base balance variables and plasma lactate concentration [La]pl were taken at the end of each 3-minute step. The lactate threshold (LT) in this study was defined as the highest power output above which [La]pl showed a sustained increase of > 0.5 mmol.l-1.step-1. The power output at LT amounted to 127 +/- 28 W. It corresponded to 45% of the maximal power output (MPO) reached at maximal oxygen uptake (VO2 max). The oxygen uptake at the LT amounted to 1734 +/- 282 ml.min-1 and corresponded to 48% of VO2 max (3726 +/- 363 ml.min-1). The minute ventilation at the LT amounted to 47.8 +/- 7.5 l, and its increase to the level of 125.7 +/- 19.7 l reached at the MPO was obtained mainly by intensification of breathing frequency from 23.8 +/- 3.31.min-1 to 43 +/- 5.91.min-1, for LT and MPO respectively. Analysis of the changes in PETCO2 during the incremental exercise test showed significant differences between subjects. One could recognise a group of subjects (n = 8) with high values of PETCO2 (above 45 mmHg) and a group of subjects (n = 8) with lower values of PETCO2 (below 43 mmHg). However, no significant differences in exercise tolerance, expressed by the level of MPO and maximal oxygen uptake, were found between those groups of subjects. The mechanical efficiency calculated on the basis of power output/net oxygen uptake ratio during cycling at a power output of 60 W amounted to 24.1 +/- 3.8 percent, at the LT 25.8 +/- 2.1%, whereas at the maximal power output a significant (p < 0.01) drop in muscle efficiency occurred, to the value of 23.1 +/- 1.6%. This drop in muscle efficiency occurring at the MPO may be an important factor limiting exercise tolerance when performing high power output exercise. In conclusion: The above presented data illustrate the physiological responses to incremental exercise and the level of exercise tolerance, which may serve as a reference point for the population of healthy, young physically active Polish students.     

Metabolic profile of high intensity intermittent exercises

To evaluate the magnitude of the stress on the aerobic and the anaerobic energy release systems during high intensity bicycle training, two commonly used protocols (IE1 and IE2) were examined during bicycling. IE1 consisted of one set of 6-7 bouts of 20-s exercise at an intensity of approximately 170% of the subject's maximal oxygen uptake (VO2max) with a 10-s rest between each bout. IE2 involved one set of 4-5 bouts of 30-s exercise at an intensity of approximately 200% of the subject's VO2max and a 2-min rest between each bout. The accumulated oxygen deficit of IE1 (69 +/- 8 ml.kg-1, mean +/- SD) was significantly higher than that of IE2 (46 +/- 12 ml.kg-1, N = 9, p < 0.01). The accumulated oxygen deficit of IE1 was not significantly different from the maximal accumulated oxygen deficit (the anaerobic capacity) of the subjects (69 +/- 10 ml.kg-1), whereas the corresponding value for IE2 was less than the subjects' maximal accumulated oxygen deficit (P < 0.01). The peak oxygen uptake during the last 10 s of the IE1 (55 +/- 6 ml.kg-1.min-1) was not significantly less than the VO2max of the subjects (57 +/- 6 ml.kg-1.min-1). The peak oxygen uptake during the last 10 s of IE2 (47 +/- 8 ml.kg-1.min-1) was lower than the VO2max (P < 0.01). In conclusion, this study showed that intermittent exercise defined by the IE1 protocol may tax both the anaerobic and aerobic energy releasing systems almost maximally.     

Can pre-emptive lumbar epidural blockade reduce postoperative pain following lower abdominal surgery?

Pharmacokinetics and ventilatory effects of a single intravenous dose of 0.5 mg/kg of pentazocine were studied in ten children aged 4 to 8 years after ophthalmic surgery. Elimination half-life (mean +/- S.D.) was 3.0 +/- 1.5 hr and clearance 21.8 +/- 5.9 ml/min./kg. The values for Vc, Vss and V beta were 0.73 +/- 0.21, 4.0 +/- 1.2 and 5.3 +/- 2.1 l/kg, respectively. The pharmacokinetic parameters were similar to those of adults. After administration of pentazocine decrease in ventilatory rate and oxygen saturation and increase in end-tidal carbon dioxide were relatively fast and steep. Oxygen saturation of four patients decreased below 90% and in one patient the decrease did not recover instantly and additional oxygen was given for 2 min. No patient needed assisted ventilation. Only clinically insignificant changes in heart rate and mean arterial pressure were observed. The duration of analgesia was 164 +/- 59 min. No serious side-effects appeared.     

Antiarrhythmic action of the new calcium antagonist [1,2,5-trimethyl-4-phenyl-4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine dihydrochloride

Arrhythmias induced by coronary artery ligation in cats, by CaCl2 and epinephrine in rats, and by ouabain in guinea-pigs were used as experimental models for studying the effects of a new calcium antagonist AR-1 ([1,2,5-trimethyl-4-phenyl-4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine, calcium channel blocker and calmodulin antagonist) on ventricular arrhythmias. Coronary ligation caused 90% lethality (ventricular fibrillation) with 12.5 min in untreated control cats, which was prevented by administration of AR-1 (4 mg/kg body weight (b.w.) before or after arrhythmia induction. Pretreatment with AR-1 afforded protection in a dose-related fashion. A dose of 1.5 mg/KG b.w. increased survival to 45%, and all cats dosed with 3 to 5 mg/Kg b.w. survived. CaCl2 (180 mg/Kg b.w., i.v.) induced ventricular fibrillation and 100% lethality. These effects were completely prevented by an anti-arrhythmic dose of AR-1 (3 mg/kg b.w.). Epinephrine-induced ventricular arrhythmias were also prevented by the same dose of AR-1. AR-1 (5 mg/kg b.w.) did not prevent ouabain (0.5 mg/kg b.w.)-induced arrhythmias that caused death within 17 +/- 3.7 min, but displayed protective effects during 67 +/- 7.7 min. The results from these animal studies, in conjunction with previously studies demonstrating coronarodilatory and anti-platelet efficacy of this compound, collectively suggest that AR-1 has a potential to become a useful antianginal and antiarrhythmic therapeutic agent.     

Pediatric hepatic trauma: does clinical course support intensive care unit stay?

PURPOSE: The objective of this study is to determine if grade of liver injury predicts outcome after blunt hepatic trauma in children and to initiate analysis of current management practices to optimize resource utilization without compromising patient care. METHODS: A retrospective review of 36 children who had blunt hepatic trauma treated at a pediatric trauma center from 1989 to present was performed. Hepatic injuries graded (AAST Organ Injury Scaling) ranged from grade I to IV. Injury Severity Score (ISS), Glasgow Coma Score (GCS), transfusion requirements, liver transaminase levels, associated injuries, intensive care unit (ICU) length of stay, and survival were analyzed. RESULTS: Mean (+/-SEM) age was 6.6+/-0.8 years, mean grade of hepatic injury was 2.4+/-0.2, mean ISS was 17+/-2.6, mean GCS was 13+/-1, and mean transfusion was 15.4 mL/kg of packed red blood cells (PRBC). There were three deaths with a mean ISS of 59+/-9 and a mean GCS of 3+/-0. Death was not associated with a high-grade liver injury, survivors versus nonsurvivors, 2.3+/-0.2 versus 2.7+/-0.3, but was associated with ISS, 13+/-1.4 versus 59+/-9 (P = .005) and GCS, 14+/-1 versus 3+/-0 (P = .005). Only one patient (grade III, ISS = 43) underwent surgery. There were no differences in mean ISS or GCS between grades I to IV patients. The hepatic injury grades of patients requiring transfusion versus no transfusion were significantly different, 3.4+/-0.2 versus 2.2+/-0.2 (P = 0.04). Abused patients had high-grade hepatic injuries and significant laboratory and clinical findings. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in grade III and IV injuries than in grades I and II, 1,157+/-320 versus 333+/-61 (P= .02) and 1,176+/-299 versus 516+/-86 (P= .04), respectively. No children with grade I or II injury had a transfusion requirement or surgical intervention. There were no liver-related complications. CONCLUSIONS: Mortality and morbidity rates in pediatric liver injuries, grades I to IV, correlate with associated injuries not the degree of hepatic damage. ALT, AST, and transfusion requirements are significantly related to degree of liver injury. Low-grade and isolated high-grade liver injuries seldom require transfusion. Blunt liver trauma rarely requires surgical intervention. In retrospect, the need for expensive ICU observation for low-grade and isolated high-grade hepatic injuries is questionably warranted.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

The effect of promethazine hydrochloride on bilirubin metabolism in the rat

The effect of 21 days of promethazine-HC1 administration on hepatic bilirubin metabolism and transport was studied in adult rats. A significant increase in mean cumulative hepatic bilirubin uptake (84.5 +/- 7.6 (SE) mug/100 g/min in controls vs. 110.0 +/- 4.3 in treated rats), mean hepatic glucuronide conjugation (1,330 +/- 86 (SE) mug bilirubin conjugated/g liver/40 min in controls vs. 1.713 +/- 61 in treated rats), and mean maximal hepatic excretion (47.2 +/- 4.9 (SE) mug/100 g/min vs. 63.5 +/- 2.7) was observed in treated animals. Mean total liver weight and total hepatic protein also increased significantly. These observations suggest that promethazine is an inducer of protein and enzyme synthesis in rat liver and is capable of significantly stimulating the three major steps in hepatic disposal of bilirubin.     

Physiological, metabolic and biochemical responses of horses competing in the speed and endurance phase of a CCI*****3-day-event

The present study was undertaken to investigate physiological, metabolic, haematological and biochemical changes in horses competing in the Speed and Endurance test of a Concours Complet International (CCI)*****3-day-event held under FEI rules. A total of 28 horses competing in the Burghley Horse Trials Speed and Endurance test were selected to be monitored: 11 horses in 1993 and 17 horses in 1994. Of the 28 horses selected, 17 completed the Speed and Endurance test and went on to complete the showjumping test. Mean +/- s.d. shade temperature and relative humidity, black globe temperature and wind speed were 13 +/- 1 and 20 +/- 2 degrees C, 54 +/- 3 and 55 +/- 10%, 17 +/- 2 and 29 +/- 4 degrees C and 2.7 +/- 0.7 and 1.2 +/- 0.3 m/s, for 1993 and 1994, respectively. Mean heart rate during Phases A, B and D was not significantly different between years, but mean heart rate during Phase C and X was significantly higher in 1994. Mean (+/- s.d.) heart rate on Phase B and D for all horses in both 1993 and 1994 was 198 +/- 8 and 188 +/- 11 beats/min, respectively. Mean heart rate during Phase D showed a poor correlation with mean speed (r = 0.412). Total mean (+/- s.d.) weight loss from the start of Phase A to the end of Phase D was 15.5 +/- 6.1 kg in 1993 and 16.5 +/- 5 kg in 1994 and did not differ significantly between years. Following 14-18 h completion of Phase D, mean bodyweight was not significantly different from that at the start of Phase A in either year. Mean rectal temperature at the end of Phase D was 41 +/- 0.6 degrees C and 41.1 +/- 0.6 degrees C in 1993 and 1994, respectively (P > 0.05). Both the lowest (39.7 degrees C) and highest (41.8 degrees C) rectal temperatures were recorded at the end of Phase D in 1994. Plasma lactate concentrations at the end of Phase D were 8.5-38.5 mmol/l. The highest lactate concentration also coincided with the highest plasma glucose concentration (11.4 mmol/l) as well as the joint fastest time in either year, although overall lactate showed only weak correlations with mean speed on Phase D (r = 0.12, 1993; r = 0.58, 1994). While the Speed and Endurance test at CCI*****level run in a temperate climate presents a considerable challenge to the fitness and ability of the horses competing, the metabolic and physiological changes are not extreme. The majority of horses that finish the test appear to undergo a rapid and considerable degree of recovery and are able to present sound at the final inspection, take part in the showjumping test and complete the competition.     

A model for the extended studies of hepatic hemodynamics and metabolism in swine

To our knowledge postoperative hepatic hemodynamics and hepatic metabolism have not been fully studied on a long-term basis. Our goal was to develop a large animal model that would permit the measurement of hepatic blood flow (BF), perihepatic pressures (P), and hepatic metabolism in a long-term setting. Catheters were inserted into the jugular vein, carotid artery, pulmonary artery, hepatic vein, and portal vein (PV) of 27 commercially bred pigs; ultrasonic transit time flowmeter probes were placed around the hepatic artery and PV. Daily postoperative measurements of jugular vein P, carotid artery P, pulmonary artery P, hepatic vein P, and PVP, as well as hepatic artery BF and PVBF, were recorded for 20 days. Hepatic carbohydrate metabolism was assessed by arteriovenous difference techniques. Jugular vein P, pulmonary artery P, hepatic vein P, PVP, and heart rate reached steady-state values during the first week, with a mean +/- SEM of 1.0 +/- 0.3 mm Hg for jugular vein P, 21.4 +/- 2.1 mm Hg for pulmonary artery P, 4.3 +/- 0.4 mm Hg for HVP, 7.8 +/- 0.5 mm Hg for PVP, and 116 +/- 4 beats per minute for heart rate. Mean carotid artery P increased from 65 +/- 3 mm Hg during surgery to 94 +/- 2 mm Hg on postoperative day 1 (P < 0.001) and to a mean 101 +/- 2 mm Hg thereafter. Total hepatic BF reached a steady-state value of 1,132 +/- 187 ml/min by postoperative day 7 (P = 0.19). Over week 1 hepatic artery BF measured as a percentage of total hepatic BF decreased from 35.0 +/- 3.0% to 15.5 +/- 2.7%, and PVBF increased from 65.0 +/- 3.0% to 84.5 +/- 2.7% (P < 0.005); both variables were steady thereafter. In the hemodynamic steady state the net hepatic balances of glucose, lactate, glycerol, and alanine in 5 pigs were 9.9 +/- 4.0, -4.2 +/- 0.4, -2.3 +/- 1.1, and -0.68 +/- 0.22 micromol/kg per min respectively. The net gut (portal-drained viscera) balances of glucose, lactate, alanine, and glycerol were -2.0 +/- 2.5, 1.1 +/- 0.5, 0.73 +/- 0.18, and -0.69 +/- 0.19 micromol/kg per min respectively. Thus, a reliable large animal model was developed to study acute and chronic hepatic hemodynamics and metabolism.     

Hemin: levels in experimental subarachnoid hematoma and effects on dissociated vascular smooth-muscle cells

Although hemin is known to exert toxic effects on a variety of cell types, its possible participation in the genesis of cerebral vasospasm has received little attention. The authors measured the concentration of hemin in experimental subarachnoid clot and studied its effects on the morphology and 45Ca++ uptake of vascular smooth-muscle cells dissociated from canine carotid artery. Craniectomies were performed in five dogs under general anesthesia, and 3 to 5 ml of autologous whole blood was deposited in the supraclinoid subarachnoid compartment. The concentration of hemin recovered by Folch extraction from clotted material removed 7 days after surgery was 390 +/- 247 microM (mean +/- standard error of the mean). Mean vascular smooth-muscle cell length after 40 minutes of exposure to 50 microM hemin was 37.3 +/- 1.2 microns (control 51.6 +/- 1.6 microns) (p < 0.01). The mean percent permeation of 45Ca++, measured by a dual label technique, of cells exposed to hemin was 200.9% +/- 23% (control 102.9% +/- 4.3%) (p < 0.01). These findings indicate that hemin accrues in subarachnoid hematoma, that it exerts a constrictive effect on vascular smooth-muscle cells, and that this effect is associated with an increased uptake of Ca++. This study demonstrates that hemin should be included in the list of potential agents that participate in the development of cerebral vasospasm.     

Diagnosis of middle cerebral artery stenosis by transcranial color-coded real-time sonography

BACKGROUND & PURPOSE: This study was performed to determine the usefulness of transcranial color-coded real-time sonography (TCCS) in detecting stenosis in the horizontal portion of the middle cerebral artery (MCA). METHODS: Using TCCS and the incident angle correction technique, we measured the peak-systolic flow velocity in bilateral MCAs in 45 consecutive patients in whom cerebral angiography was carried out within 1 week before or after TCCS. Three patients had a stenosis of 75% or greater and four had a unilateral occlusion of the extracranial internal carotid artery (ICA) (the ICS and ICO groups, respectively). Eight patients had a stenosis of 50% or greater (one bilateral and seven unilateral) (the M1S group). Four patients had unilateral distal occlusion of the horizontal portion of the MCA (the M1O group). Twenty-six patients had no significant extra- or intracranial stenosis on the ipsilateral or contralateral side (the control group). RESULTS: Mean peak-systolic flow velocity on the affected side was 83.0 +/- 20.8 cm/s in the ICS group, 59.8 +/- 23.2 cm/s in the ICO group, and 62.3 +/- 33.7 cm/s in the M1O group. In the control group, the mean peak-systolic flow velocity was 116.0 +/- 31.5 cm/s. In the M1S group, however, the mean peak-systolic flow velocity (334.2 +/- 35.7 cm/s) on the affected side always exceeded 180 cm/s (mean value +/- 2 SD in the control group), and was significantly higher than that in the other groups. The mean peak-systolic flow velocity in the M1S group increased with the grade of stenosis. CONCLUSION: The M1S group members could easily be distinguished from the other group members by their peak-systolic flow velocity in excess of 180 cm/s. Measurement of the peak-systolic flow velocity of the MCA by TCCS may help to identify a significant stenosis in the horizontal portion of the MCA.     

The macrophage and cancer

An adaptation of a standard activity wheel has been used to determine oxygen uptake of rats prior to and during exercise at 7 different speeds (16-67 m/min). Pre-exercise oxygen uptake was 2.42 +/- 0.10 (S.E.) ml (100 g x min)-1. Oxygen uptake increased linearly with work intensity (running speed). At 16m/min oxygen uptake was 6.44 +/- 0.16 ml (100 g x min)-1 and it increased to a maximal value of 9.51 +/- 0.14 ml (100 g x min)-1 at a running speed of 53.6 m/min. Increasing running speed to 67 m/min did not produce any further increase in oxygen uptake. Some comparisons of exercise intensity between rats of various studies and rats and man can be made from these data.     

Introducing fluorine-18 fluoromisonidazole positron emission tomography for the localisation and quantification of pig liver hypoxia

Fluorine-18 labelled fluoromisonidazole ([18F]FMISO) has been shown to accumulate in hypoxic tissue in inverse proportion to tissue oxygenation. In order to evaluate the potential of [18F]FMISO as a possible positron emission tomography (PET) tracer for imaging of liver tissue hypoxia, we measured the [18F]FMISO uptake in 13 domestic pigs using dynamic PET scanning. Hypoxia was induced by segmental arterial hepatic occlusion. During the experimental procedure the fractional concentration of inspired oxygen (FiO2) was set to 0.67 in group A (n=6) and to 0.21 in group B (n=7) animals. Before and after arterial occlusion, the partial pressure of O2 in tissue (TPO2) and the arterial blood flow were determined in normal flow and flow-impaired liver segments. Standardised uptake values [SUV=kBq tissue (in g) / body weight (in kg) x injected dose (in kBq)] for [18F]FMISO were calculated from PET images obtained 3 hours after injection of about 10 MBq/kg body weight [18F]FMISO. Immediately before PET scanning, the mean arterial blood flow was significantly decreased in arterially occluded segments [group A: 0. 41 (0.32-0.52); group B: 0.24 (0.16-0.33) ml min-1 g-1] compared with normal flow segments [group A: 1.05 (0.76-1.46); group B: 1.14 (0.83-1.57) ml min-1 g-1; geometric mean (95% confidence limits); P<0.001 for both groups]. After PET scanning, the TPO2 of occluded segments (group A: 5.1 (4.1-6.4); group B: 3.5 (2.6-4.9) mmHg] was significantly decreased compared with normal flow segments [group A: 26.4 (21.2-33.0); group B: 18.2 (13.3-25.1) mmHg; P<0.001 for both groups]. During the 3-h PET scan, the mean [18F]FMISO SUV determined in occluded segments increased significantly to 3.84 (3.12-4.72) in group A and 5.7 (4.71-6.9) in group B, while the SUV remained unchanged in corresponding normal liver tissue [group A: 1.4 (1.14-1. 71); group B: 1.31 (1.09-1.57); P<0.001 for both groups]. Regardless of ventilation conditions, a significant inverse exponential relationship was found between the TPO2 and the [18F]FMISO SUV (r2=0. 88, P<0.001). Our results suggest that because tracer delivery to hypoxic tissues was maintained by the portal circulation, the [18F]FMISO accumulation in the liver was found to be directly related to the severity of tissue hypoxia. Thus, [18F]FMISO PET allows in vivo quantification of pig liver hypoxia using simple SUV analysis as long as tracer delivery is not critically reduced.     

Bacteraemia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection

OBJECTIVE: The main objective of this study was to evaluate the effect of switching from parenteral to enteral feeding on liver blood flow and propofol steady-state blood concentrations in patients in the intensive care unit (ICU). DESIGN AND PATIENTS: Steady-state blood concentrations of propofol were measured in eight ICU patients before (on days D -3, D -2, and D -1) and after (on days D + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day DO). All patients received a continuous intravenous infusion of propofol (4.5 mg x kg(-1) x h(-1)) from several days before the start of the study, continuing throughout the experimental period. Hepatic blood flow was estimated by measuring steady-state D-sorbitol hepatic clearance. RESULTS: Hepatic blood flow was high and was not affected by switching from parenteral to enteral feeding: 33 +/- 8 ml x min(-1) x kg(-1) (mean +/- SD) and 33 +/- 10 ml min(-1) x kg(-1) on D -3 and D -1, respectively, as compared to 37 +/- 11 ml x min(-1) kg(-1) and 34 +/- 8 ml x min(-1) x kg(-1) on days D + 1 and D + 3, respectively. Systemic clearance of propofol was much higher than liver blood flow with average values on the six observation days ranging from 74.0 to 81.2 ml x min(-1) x kg(-1) and was not affected by switching from parenteral to enteral feeding. CONCLUSIONS: Liver blood flow and systemic clearance of propofol were not affected by switching from parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic clearance accounted for at least two thirds of the overall systemic clearance of propofol.