A study of factors governing fluid filtration in the diabetic foot

Abstract. The effect of lowering the foot on the factors governing fluid filtration in the foot were studied in 12 male insulin-dependent diabetic subjects and 10 controls. Toe skin blood flow, measured by laser Doppler flowmetry, was significantly higher during dependency in the diabetic group. In the control subjects, the colloid osmotic pressure of venous blood sampled from the foot rose to 47·7 mmHg (range 45·1–53·8) after 50 min of foot dependency. In the diabetic group, colloid osmotic pressure failed to rise to the same extent (median 36·7 mmHg; range 28·6–43·0; P < 0·001). Capillary pressure, measured directly by the Landis microinjection technique, was significantly higher in the diabetic group (85·3±1·7 ( n = 6) vs. 92·2±4·6 cm H₂O ( n = 6); P < 0·007), as was foot swelling rate determined by mercury strain gauge plethysmography (0·069±0·022 vs. 0·099±0·025 ml min^-1 100ml^-1; P < 0·02). These results suggest an impairment of the oedema-preventing mechanisms in diabetic subjects which may contribute to the risks of ulceration in the diabetic foot.     

Reduced pressor effect of angiotensin II and of noradrenaline in normal man following the oral administration of the calcium-antagonist nifedipine

Abstract. The pressor response to both angiotensin II (5, 10 and 20 ng kg^-1min^-1) and to noradrenaline (50, 100 and 200 ng kg^-1 min^-1) was reduced ( P < 0·05 to < 0·005) in six healthy male subjects following the administration of the calcium-antagonist nifedipine (10 mg p.o.). Nifedipine induced a rise in basal plasma noradrenaline concentrations but did not alter the plasma concentrations of adrenaline, dopamine, renin and aldosterone. A slight reduction in the angiotensin II induced rise of plasma aldosterone by nifedipine was observed after the administration of the largest dose of angiotensin II only ( P < 0·05). The reduced responsiveness towards pressor agents following oral nifedipine is in keeping with the known antihypertensive effect of calcium-antagonistic drugs and could provide a concept for the effectiveness of these drugs in hypertensive crisis.     

Effects of insulin-like growth factor-I (IGF-I), insulin and combined IGF-I-insulin infusions on protein metabolism in dogs

Abstract The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min^-1 kg^-1), insulin (3·4, 10·3 or 68·8 pmol min^-1 kg^-1) or combined infusions (34 pmol IGF-I+ 3·4 pmol min^-1 kg^-1 insulin or 103 pmol IGF-I+ 3·4 pmol min^-1 kg^-1 insulin) on protein metabolism, using an infusion of [1-¹⁴C] leucine was investigated in anaesthetized fasted dogs. Leucine concentration, production rate (measure of protein degradation), oxidation rate and non-oxidative disappearance rate (measure of protein synthesis) were decreased in a similar dose dependent manner by the IGF-I and insulin infusions (P <0·01). The decrease in these measurements of leucine metabolism were greater following 34 pmol IGF-I + 3·4 pmol insulin than with either component infused alone (P <0·05). Free fatty acid concentrations were decreased by all insulin doses (P < 0·01) but only by 103 and 688 pmol min^-1 kg^-1 insulin-like growth factor (P < 0·05, P < 0·01). These data demonstrate that IGF-I, like insulin, has a dose dependent effect on protein metabolism and that combined insulin and IGF-I infusions have additive effects on protein metabolism.     

Familial benign hypercalcaemia: a possible abnormality in calcium transport by erythrocytes

Abstract. The fundamental biochemical abnormality in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) is unknown. It seemed possible that, since the kidneys and the parathyroid glands are insensitive to the high extracellular calcium levels, a general disorder of the regulation of the calcium pump on the plasma membrane is present. We obtained evidence suggesting that active calcium efflux by erythrocytes from patients with FBH (85·7 pL 4·5 μmol l^-1 min^-1) is higher ( P < 0·005) than that by erythrocytes from control subjects (78·6 pL 4·1 μmol l^-1 min^-1) or from patients with primary hyperparathyroidism (77·5 pL 5·2 μmol l^-1 min^-1, P < 0·05). Calcium influx into erythrocytes was normal in FBH and in primary hyperparathyroidism.     

Time course of haemodynamic changes after maximal exercise

Abstract. The haemodynamic changes during 4 h following maximal upright bicycle exercise were evaluated in six normals in a randomized controlled crossover design. Total peripheral resistance was reduced to 2 h (-6·7 mmHgmin l^-1, P < 0·05); exercising and non-exercising vascular beds were vasodilated for 2h (-24·1 and -23·8 mmHg min ml^-1 100ml^-1 tissue, respectively, P < 0·05), associated with reductions in systolic (-5·8 mmHg, P < 0·05) and diastolic pressure (-8·3mmHg, P < 0·05). Rise in cardiac index for 1 h (+0·51min^-1 m^-2, P < 0·05) was accounted for by an elevated heart rate (+14·4 beats min^-1, P < 0·01) as stroke volume was unchanged. Body temperature was elevated until 40min (+0·20°C, P < 0·05). The return of all haemodynamic variables to control by 3h suggests a 3 h limit for a hypotensive effect of exercise. Rise in body temperature is not the only factor responsible for the hypotension.     

Microdialysis assessment of adipose tissue metabolism in post-absorptive obese NIDDM subjects

Abstract. Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis combined with ¹³³Xe clearance and measurements in arterialized plasma were carried out using samples of subcutaneous abdominal fat from nine obese NIDDM subjects (glucose, 7.9 ± 0.7 mmol L^-1) (mean±SEM) and nine obese non-diabetic subjects (glucose, 4.9 ±0.1) matched for age, BMI and body fat. After an overnight fast arterialized plasma levels were 1145 ±110 vs. 876 ±59 μmol L^-1 ( P <0.05) for lactate and 75±10 vs. 66 ±8 μmol L^-1 for glycerol in the diabetic and control group, respectively. The corresponding abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278 ± 63 vs 1107 ±64 μmolL^-1 and 314 ±28 vs. 311 ± 17μmol L^-1, respectively. However, adipose tissue blood flow in the same region was lower in NIDDM subjects (1.5±0.2 vs 2.4±0.3 mL 100g^-1 min^-1) ( P <0.05). Consequently, apparent subcutaneous lactate and glycerol release, estimated according to Fick, were not statistically different in the two groups (1.8 ±0.4 vs 2.4 ±0.8 and 2.1 ±0.4 vs 3.1 ±0.5 μmol kg^-1 min^-1 in NIDDM and control subjects, respectively). Thus, in the post-absorptive state apparent lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM subjects was similar to that in a matched group of obese non-diabetic controls. The data suggest that no primary defect is evident in adipose tissue metabolism in well controlled NIDDM subjects.     

The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide (GIP) in man

Abstract. The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide were investigated in six healthy volunteers. At the maximum infusion dose (0·5 pmol kg^-1 min^-1) a plateau concentration of 115 ± 5·0 pmol/l plasma was obtained. On discontinuation of the infusion, the half-time of disappearance was calculated to be 20·3 ± 1·2 min. The metabolic clearance rate was 2·6 ± 0·1 ml kg^-1 min^-1 and the apparent space of distribution was 75·8 ± 5·7 ml kg^-1. Blood glucose, pancreatic and gastrointestinal hormones remained at basal concentrations throughout. No side effects were noted by any of the subjects studied.     

The individual variation in pharmacokinetics and pharmacodynamics of furosemide in young normal male subjects

Abstract. Following a 24 h control period in the ward 80 mg furosemide was injected intravenously to ten young healthy, male volunteers. The serum clearance of furosemide (Cl_s) was between 140 and 201 ml min^-1 and on the average the renal clearance was 66% of Cl_s. During the initial 30 min period a maximum additional excretion rate of sodium of 3·3 mmol min^-1 was reached at an excretion rate of 0·8 mg furosemide min^-1. A marked initial drop in creatinine clearance (Cl_cr) was noted and Cl_{cr(24 h)} showed an average decrease of 12% after the drug administration. The serum concentration of potassium was decreased at 1 and 2 h after the injection and of sodium from 2 h and on. The concentration of albumin in serum increased by 3% ( P < 0·05) already after 5 min. After 2 h a maximum increase of 14% was reached. After 8 min diastolic blood pressure was increased by 13% ( P < 0·05), whereas systolic blood pressure reached a significant decrease gradually (7% after 3 h).     

Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria

Abstract. Two enzymes of the haem biosynthetic pathway were investigated in patients with variegate porphyria. Protoporphyrinogen oxidase in cultures of Epstein-Barr virus transformed lymphoblasts from twenty-seven patients showed a mean maximal velocity ( V _max) of 0·39 ± 0·08⁺ nmol of protoporphyrin mg protein^-1 h^-1, a 52% reduction ( P < 0·001) from a non-porphyric control group (0·82 ± 0·10). K _m values (1·00 ± 0·27 μ M) did not differ significantly ( P > 0·05) from control values in any of the patients. The mean V _max of porphobilinogen deaminase in the cultures was 1·50 ± 0·18 nmol of uroporphyrin mg protein^-1 min^-1, a 24% reduction ( P < 0·001) from controls (1·94 ± 0·14). Mean porphobilinogen deaminase activity in the erythrocytes of twenty-one patients with variegate porphyria was 8·37 ± 1·99 nmol of uroporphyrin 1 erythrocytes^-1 s^-1, a 28% reduction ( P < 0·001) from normal (11·98 ± 2·11). The reduced activities of these two enzymes comply with the expression of variegate porphyria during its quiescent and acute phases.     

Kinetics of circulating hyaluronan in humans

Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA were given, separated by 90 min washout periods. Blood samples were taken before, during and after each infusion and the plasma HA concentration was determined. The deposition of HA was modelled according to a Michaelis–Menten kinetic model which included natural synthesis of HA. K_m and V_max was estimated to 0·34 ± 0·13 μgml^-1 and 3·48 ± 0·97/μmin^-1kg^-1 b.w., respectively. The endogenous input was calculated to be 24 ± 11 μg min^-1 and was found to correlate to the age of the subjects ( P < 0·05). As the baseline HA concentration was 0·031 ± 0·21 μg ml^-1, the rate of elimination was linear in the normal concentration range. The calculated V_d was about 75% higher than a weight-estimated plasma volume. The total amount of HA excreted by the kidneys during the study period was 394 ± 77 μg, which corresponded to approximately 1·7% of the total input of HA into the circulation during the experiment.     

Acute effect of smoking on fibrinolysis: increase in the activity level of circulating extrinsic (tissue-type) plasminogen activator*

Abstract. The acute effect of cigarette smoking on the fibrinolytic enzyme system in blood was studied. It was found imperative to have an initial 30 min rest period, after venipuncture, to obtain a stable baseline in the fibrinolytic studies.
The average heart rate, in inhaling smokers, increased from 64 to a peak of 79 beats min^-1 5–10 min after commencement of smoking. A peak in fibrinolytic activity was found to occur later, at 22·5 min. Analysis of the increase in fibrinolytic activity revealed no demonstrable activation of intrinsic systems via factor XII, nor changes in plasminogen, prekallikrein and C1-inactivator. No plasmin- α ₂-antiplasmin complexes were detectable. The increase ( P <0·01) was found to be due to extrinsic (tissue-type) plasminogen activator, revealed as C1-inactivator-resistant plasminogen activator activity, and further identified by quenching with anti-tissue plasminogen activator IgG.
Thus, smoking appears to elicit a significant increase in the level of activity of circulating extrinsic plasminogen activator.     

Venous compliance and the venodilatory effect of nitroglycerin in insulin-dependent diabetic patients with and without (incipient) nephropathy

Abstract. The venous system plays a pivotal role in volume and blood pressure homeostasis. We tested the hypothesis that the visco-elastic properties of the peripheral venous system are reduced in patients with (incipient) diabetic nephropathy. Twenty-two normotensive patients with long-term insulin-dependent diabetes mellitus (IDDM), 11 without and 11 with (incipient) nephropathy (eight microalbuminuria and three proteinuria, serum creatinine below 100 μmol l^-1), and 14 healthy age/sex matched controls were studied. Forearm venous compliance (VENCOMP) was determined using strain gauge plethysmography and direct intravenous pressure measurements. Furthermore, the venodilatory effect of 0·4 mg sublingual nitroglycerin (NTG) was studied. In comparison with healthy controls, VENCOMP was decreased in patients without and with (incipient) nephropathy, without any differences between the two diabetic groups: 0·059 (0·052–0·066), 0·044 (0·038–0·059) and 0·049 (0·046–0·058) ml 100 ml^-1 mmHg^-1, respectively (medians and interquartile ranges) ( P <0·05). No differences in the increase of forearm volume after NTG were observed: 0·34 (0·11–0·51), 0·37 (0·19–0·50) and 0·39 (0·20–0·55) ml 100 ml^-1, respectively. In conclusion, the visco-elastic properties of the peripheral venous system are reduced in patients with long-term IDDM. This reduction is not related to the presence of nephropathy. No major differences were observed in NTG-induced venodilation between diabetic patients and healthy subjects.     

Distal renal tubular dysfunction: a common feature in calcium stone formers

Abstract. Distal renal tubular acidosis has been reported as an uncommon cause of urinary calcium stone disease. However, this defect appears to be more frequent when appropriate tests are performed systematically. Twenty-nine patients with recurrent calcium stones have been separated into three groups: normocalciuric (group A), renal hypercalciuric (group B) and absorptive hypercalciuric (group C). Distal tubular functions were investigated by the (urine-blood) pCO₂ gradient and by an ammonium chloride test. (Urine–blood) pCO₂ gradient was (mean pL SEM), 3·33 pL 0·59 in group A, 2·95 pL 0·34 in group B and 3·31 pL 0·58 kPa in group C. All these values differ significantly from those observed in controls (4·11 pL 0·28 kPa; P < 0·05). After 3 days of ammonium chloride loading, ammonium excretion averaged 54·7 pL 4·2 in group A, 54·4 pL 4·3 in group B and 64·3 pL 5·5 μmol min^-1 in group C. Values obtained in the first two groups were significantly lower than that achieved by control subjects (76·4 pL 14·9 μmol min^-1). It is concluded that tubular dysfunctions defined as impairments in hydrogen ion secretion and ammonium excretion after an acid challenge are a common feature of the urinary calcium stone disease and play a contributory role in its pathogenesis.     

Vascular reactivity to noradrenaline and neuropeptide Y in the streptozotocin-induced diabetic rat

Abstract. The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se . The authors compared non-diabetic rats ( n = 9) and rats with streptozotocin-induced diabetes that were either untreated ( n = 10), or treated with insulin ( n = 9) or food restriction ( n = 8) to restore near-normoglycaemia. After 4 weeks of diabetes, contractile responses to noradrenaline (0.24–48 μmolL^-1), without and with neuropeptide Y (0.1 μmolL^-1), were assessed using an isometric myograph in two mesenteric arteries from each rat. Vessels from untreated diabetic rats were significantly more reactive to noradrenaline than the control vessels when tested without ( P <0.0001) but not with ( P = NS) neuropeptide Y. Diabetic rats rendered nearly normoglycaemic through food restriction showed dose-response curves that were very similar to the untreated diabetic group ( P = NS). By contrast, insulin-treated diabetic vessels showed reduced sensitivity to noradrenaline, with and without neuropeptide Y, compared with both the diet-restricted and untreated vessels (both P μ0.0001). The authors conclude that vascular sensitivity to noradrenaline, without or with neuropeptide Y, is reduced over a wide dose range in vessels taken from rats treated in vivo with insulin; furthermore, vessels taken from diabetic rats not treated with insulin (hypoinsulinaemic) tended to be more reactive than either control vessels or those taken from the insulin-treated rats. The latter group of rats were probably hyperinsulinaemic for much of the time; the results may therefore support the hypothesis that insulin acts as a vasodilator.     

The relationship of serum total sialic acid with serum acute phase proteins and lipoprotein (a) in patients with severe hypertriglyceridaemia

Abstract. Total serum sialic acid (TSA), recently shown to be a cardiovascular risk factor, was measured in 15 patients with severe hypertriglyceridaemia (fasting triglyceride > 2·3 mmol l^-1) and 15 age and sex matched normal control subjects.
To test the hypothesis that serum TSA is related in some way to serum acute phase proteins we also measured five acute phase proteins, namely alpha-1-antichymotrypsin (ACT), alpha-1-acid-glycoprotein (AGP), alpha-2-macroglobulin (AMG), C-reactive protein (CRP) and haptoglobin (HAP) in both groups.
Of note was the significantly elevated serum TSA in the severely hypertriglyceridaemic group as compared to normal subjects. Serum TSA being 71·9 ± 11·7 mg dl^-1 and 59·6 ± 10·2 mg dl^-1 respectively ( P < 0·01 Mann-Whitney test).
Serum CRP was significantly elevated in the type IV patients as compared to controls (6·4 ± 4·5 mg l^-1 vs. 3·3 ± 1·9 mg l^-1 P <0·05 Mann Whitney test) as was serum AMG (2·1 ± 0·89 g l^-1 vs. 1·5 ± 0·53 g l^-1 P < 0·05 Mann Whitney test).
There was no correlation between serum TSA and lipoprotein (a) in either the normal or severely hypertriglyceridaemic subjects. We suggest that serum TSA could in part be related to hypertriglyceridaemia and serum acute phase proteins but that its property as a cardiovascular risk factor is not related to serum lipoprotein (a) concentrations.     

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers

Abstract. The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-²H₂]glucose (0–480 min) and in random order either IGF-I 20μg kg^-1 h^-1 (43.7 pmol kg^-1 min^-1) or insulin 0.5 mU kg^-1 min^-1 (3.4 pmol kg^-1 min^-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 ± 0.13 at baseline (150–180 min) to 0.35 ± 0.26 mg kg^-1 min^-1 ( P < 0.01) at 360min, and glucose utilization rate (Rd) increased from 1.79 ± 0.28 to 4.17 ± 0.84 mg kg^-1 min^-1 ( P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output + 37.3%± 9% ( P < 0.01), heart rate + 13%± 2% ( P < 0.01) and stroke volume + 21%± 7% ( P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 ± 0.13 to 0.34 ± 0.33 mg kg^-1 min^-1 ( P < 0.01) and FFA from 0.546 mmoll^-1 to 0.198 mmoll^-1 ( P < 0.01), glucose Rd increased from l.89 ± 0.18 to 5.41 ± l.47mg kg^-1 min^-1 ( P < 0.01) and there were no significant changes in the cardiovascular variables.     

Effect of long-term starvation on acetate and ketone body metabolism in obese patients

Abstract. The turnover of ketone bodies and acetate was evaluated as well from the disappearance rate of (3-¹⁴C)acetoacetate or (1-¹⁴C)acetate respectively as from the conversion of FFA into these metabolites in normal weight and obese overnight-fasted and in obese long-term starved patients. The disappearance rate of (1-¹⁴C)oleate was the same in all three groups.
Long-term starvation enhanced ketone body turnover almost 10-fold, whereas the disappearance rate for ketone bodies decreased from 0·035 to 0·015 min^-1. Under the same circumstances the turnover of acetate was about 1 μmol g^-1 min^-1 accounting for about 5% of FFA turnover.
Long-term starvation decreased the conversion of (1-¹⁴C)oleate into triglycerides by almost 50% and increased the (2-C)-(4-C)/(1-C) ratio of radioactivity in ketone bodies. The reincorporation of radioactivity from the (1-C)position of (1-¹⁴C)oleate into the ((2-C)-( n -C)) position of FFA, which is a measure of the reutilization of acetyl-CoA for FFA synthesis decreased significantly during long-term starvation.     

Triglyceride metabolism in human liver: studies on hepatic phosphatidic-acid phosphatase in obese and non-obese subjects

Abstract. According to current concepts, soluble phosphatidic-acid phosphatase, converting phosphatidic acid into a diglyceride, is a rate-limiting enzyme in the hepatic biosynthesis of triglycerides. The present paper is the first report on this enzyme in human liver. The enzyme activity was assayed in ammonium sulphate precipitates of cytosol obtained from human liver biopsies. The activity was stimulated by preincubation with alkaline phosphatase and inhibited by Mg-ATP, suggesting that phosphorylation-dephosphorylation may be of some importance for the expression of the activity of the enzyme. When assayed under optimal conditions, the activity obtained in liver biopsies from normal-weight gallstone patients averaged 12·8 ± 2·0 nmol min^-1 (mg protein)^-1 (mean ± SEM) ( n = 17). The enzyme activity was slightly higher in liver biopsies from morbidly obese subjects 16·4 ± 2·8 nmol min^-1 (mg protein)^-1 ( n = 14). The difference between the two groups of subjects was probably in part sex-dependent and was not statistically significant. A similar small and insignificant difference between the two groups of subjects was found when the enzyme activity was assayed in the maximally stimulated state—i.e. after incubation with alkaline phosphate.
These findings suggest that an increased capacity of the soluble phosphatidic-acid phosphatase is not of major importance for the increased triglyceride synthesis known to occur in obesity. Other factors (i.e. availability of substrate and cofactors) may be of greater importance.     

The metabolism of fibrinogen and plasminogen related to diabetic retinopathy in man

Abstract. Metabolic turnover of fibrinogen and plasminogen were studied in thirty insulin-treated diabetics and ten non-diabetic controls. 131-iodine labelled fibrinogen and 125-iodine labelled plasminogen were injected intravenously and the plasma clearance of the two proteins measured simultaneously over a period of 8 days. The diabetics were selected to represent three grades of severity of diabetic retinopathy assessed by ophthalmoscopy and fiuorescein angiography; ten patients had no significant retinopathy, ten background and ten proliferative retinopathy. Subjects were matched as closely as possible for body weight, age and duration of diabetes.
Plasma fibrinogen concentrations were higher in diabetics (3–24 g/1) than controls (2–65 g/1; P <0.025); the patients with the severest retinopathy had the highest fibrinogen concentrations (3.75 g/1). As a direct consequence of the elevation of plasma fibrinogen the catabolic rate was higher in diabetics (20.9 mg kg^-1 day^-1) than controls (140 mg kg^-1 day^-1; P < 0.025) and higher in patients with background retinopathy (24.1 mg kg^-1 day^-1) and proliferative retinopathy (22.4 mg kg^-1 day^-1) than diabetics without retinopathy (16.3 mg kg^-1 day^-1; P = 0.05). Fibrin(ogen) degradation products were detectable in all diabetics but in only one-third of controls.
Plasminogen metabolism was normal in all groups of diabetics.
It is concluded that fibrinogen metabolism is increased in diabetes and bears a relationship to diabetic retinopathy but is not accompanied by significant alterations of plasminogen metabolism.     

Lack of correlation between endotoxaemia and renal hypoperfusion in cirrhotics without overt renal failure

Abstract. Renal involvement in patients with liver cirrhosis is characterized by renal vasoconstriction, the aetiology of which remains obscure. Endotoxaemia, frequently found in patients with liver cirrhosis and renal failure, has been emphasized as a pathogenic factor.
In fifty-seven patients with liver cirrhosis without overt renal failure endotoxin plasma level (Limulus Lysate test), mean renal blood flow (MRBF) (¹³³Xe washout technique), and effective renal plasma flow (ERPF) (p-aminohippurate clearance) were determined.
MRBF was decreased in nineteen out of twenty-seven patients, averaging 1·88 ± 0·51 ml g^-1min^-1 (in fourteen controls 3·17 ± 0·51 ml g^-1ml^-1). ERPF was decreased in seventeen out of thirty patients, averaging 380±164 ml/min (in eighteen controls 624±127 ml/min). Systemic endotoxaemia was found in sixteen out of fifty-seven patients, levels ranging from 0·62 to 200 ng/ml. No significant difference in renal blood flow values was found between patients with and without endotoxaemia (MRBF = 1·78 ± 0·51 and 1·93 ± 0·52 ml g^-1min^-1 respectively; ERPF = 429±119 and 365±175 ml/min respectively). No significant difference in the frequency of endotoxaemia was found between patients with impaired and unimpaired renal blood flow. Moreover no relation was found between endotoxin plasma levels and MRBF and ERPF respectively.
In conclusion in patients with cirrhosis without overt renal failure renal vasoconstriction does not seem to be related to endotoxaemia.