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Biomedical subjects

A B Groeneveld

Publications and source records attributed to A B Groeneveld.

At least 91 records · Page 5Linked to original sources

Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens.

The metabolic response to sepsis is dependent on the hormonal status. However, reported plasma hormone levels vary widely among studies. The persistence of pulsatile secretion, as occurs normally, may explain the observed variability. To study whether pulsatile hormone secretion persists during sepsis and how it affects assessment of the hormonal status from single measurements, we measured growth hormone (GH), prolactin, cortisol, insulin, and C-peptide at 20-minute intervals for 24 hours in eight consecutive patients with severe sepsis. Twenty-four-hour averages (mean +/- SD) were 3.3 +/- 2.5 ng/mL for GH, 640 +/- 461 nmol/L for cortisol, 18.2 +/- 4.8 mU/L for insulin, and 3.4 +/- 2.9 U/L for C-peptide, at a pulse frequency between 3.3 +/- 2.7 for C-peptide and 10.2 +/- 3.4 for insulin, and an increase of the maximal value in a pulse above the preceding nadir of 131% +/- 13% for cortisol and 376% +/- 386% for GH, as assessed with Cluster analysis. Prolactin levels were below the detection limit in all but one patient, probably due to the administration of dopamine. To determine the accuracy of less frequent blood sampling regimens, we simulated different sampling strategies and compared them with the 24-hour averages. The accuracy of single samples proved inadequate for all hormones. Sampling every 20 minutes for periods of 4, 8, or 12 hours improved accuracy, but intermittent sampling every 1, 2, 4, or 6 hours during a 24-hour period yielded even more accurate results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metabolic vasodilatation with glucose-insulin-potassium does not change the heterogeneous distribution of coronary blood flow in the dog.

OBJECTIVE: The heterogeneous distribution of coronary blood flow could represent regional differences in demand, or mismatching of regional O2 supply to demand, caused by regionally exhausted vasodilatation (anatomical/mechanical factors) or by regional arteriovenous diffusional O2 shunting. Regional coronary blood flow and global myocardial oxygenation and metabolism were measured during metabolic vasodilatation with glucose-insulin-potassium (GIK). METHODS: Variables were studied before and 30 and 60 min after start of a 30 min infusion of GIK (50% glucose, 4 ml.kg-1, 8 mM KCl, and 3 U insulin.kg-1). Regional blood flows were measured by radioactive microsphere technique and cardiac output by thermodilution. Experimental subjects were six anaesthetised mongrel dogs, weighing 20-27 kg. RESULTS: GIK increased plasma osmolarity and lactate, decreased haemoglobin, and increased cardiac output by 67(29)% and systemic O2 supply by 32(13)%, at unchanged arterial and central venous pressures and heart rate. Coronary blood flow rose by 97(50)% and left ventricular O2 supply by 56(41)%. Although regional blood flows in small tissue samples of about 1 g in the left ventricle ranged from a factor 0.31 to 1.73 of mean flow, GIK did not change flow heterogeneity and regional flows significantly correlated in time. Left ventricular O2 uptake rose by 42(40)%, while venous PO2 increased and O2 extraction decreased. Global lactate uptake increased at unchanged extraction. Changes were reversed after GIK. CONCLUSIONS: GIK transiently increases myocardial O2 uptake following a raised cardiac output, caused by a hyperosmolarity induced rise in cardiac contractility rather than by haemodilution. Although myocardial O2 supply is distributed heterogeneously, the fractional rise with GIK is almost equal among regions. At constant lactate extraction, increased venous PO2 and decreased O2 extraction do not indicate overperfusion in some regions at the cost of underperfusion in others, are probably caused by a small, direct vasodilating effect of hyperosmolarity, and argue against diffusional O2 shunting. As for global O2 supply to demand, the increase in regional O2 supply is probably well adapted to regionally increased demand during GIK, so that the heterogeneous distribution of O2 supply can be explained by regional differences in demand and not by regionally exhausted vasodilatation or O2 shunting.

Animals↗

Effects of recombinant human growth hormone in patients with severe sepsis.

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.

Adult↗

Plasma endothelin levels are increased during septic shock.

OBJECTIVE: To study whether serially measured plasma concentrations of endothelin (a novel, potent, endogenous vasoconstrictor derived from endothelium and macrophages) relate to the pathophysiology and severity of human septic shock. DESIGN: Prospective analysis. SETTING: Medical ICU of a university hospital. PATIENTS: Six patients with septic shock, studied for 8 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: The initial plasma endothelin concentration was increased (14.2 +/- 5.2 [SD] vs. normal 4.2 +/- 0.7 pg/mL, p less than .05) and correlated with the Acute Physiology and Chronic Health Evaluation II score (r2 = .79, p less than .05). For pooled data, endothelin levels correlated poorly with leukocyte counts (r2 = .13), mean arterial pressure (MAP) (r2 = .16), and administered doses of dopamine (r2 = .26). In multiple regression analyses, plasma endothelin concentrations were predicted by dopamine doses and not by MAP. Plasma endothelin concentrations predicted the decrease in creatinine clearance, independently from MAP. The pooled value for correlations between endothelin levels and creatinine clearance, during the course of disease in individual patients, was statistically significant (r2 = .31). CONCLUSIONS: During septic shock, the release or production of endothelin may increase as a consequence of endothelial injury by activated leukocytes and the infusion of catecholamines, and this mechanism may relate to renal vasoconstriction and to the severity of disease.

Analysis of Variance↗

Transport of 67Ga and 111In across a membrane. Role of plasma binding and concentration gradients.

If i.v. injected radiogallium does not firmly bind to circulating transferrin in plasma, the transvascular transport of the radionuclide may be affected by diffusion of unbound radionuclide and interstitial transferrin, and may therefore not be specific for transferrin transport. Using equilibrium dialysis, the avidity of 67Ga and 111In to bind to plasma transferrin was compared by evaluating transport of unbound radionuclide across a semipermeable membrane, as a function of the plasma (transferrin) concentration gradient. One chamber of a dialysis cell was filled with human plasma and 67Ga or 111In, and the other, separated by the membrane, with increasing concentrations of plasma in normal saline. The half-time (mean +/- S.D.) for reaching equilibrium between the chambers decreased (P less than 0.05) for 67Ga from 13.1 +/- 3.3 to 4.9 +/- 1.6, 3.7 +/- 1.2 and 3.0 +/- 0.5 h, at plasma concentrations of 0, 25, 50 and 100%, respectively. The equilibrium half-time for 111In did not fall at increasing plasma concentrations and was higher (P less than 0.005) than for 67Ga at 25 to 100% plasma. Hence, 67Ga is not as avidly bound to plasma transferrin as 111In, since, in contrast to 111In, dissociation of the 67Ga-transferrin complex and transmembrane diffusion of unbound 67Ga increases when the plasma transferrin concentration gradient decreases. In vivo, the transvascular transport of 67Ga may be influenced by diffusion of unbound radionuclide, depending on the interstitial transferrin concentration, and may not be a specific indicator of transvascular protein transport.

Biological Transport↗

Plasma lipid peroxides and antioxidants in human septic shock.

In order to assess if an oxidant/antioxidant imbalance is involved in human septic shock and its outcome, we measured plasma levels of the lipid peroxides malondialdehyde--as thiobarbituric acid reactive substance--conjugated dienes and fluorescent products, together with the antioxidants alpha-tocopherol, glutathione peroxidase activity and selenium in 12 patients with septic shock and compared them with values of normal controls. At first measurements, malondialdehyde (median 3.9 mumol/l; range 2-38.8) and fluorescent products (median 21.2%; range 9.4-134) were elevated (p less than 0.05), alpha-tocopherol (median 15 mumol/l; range 7-25) and selenium (median 0.76 micrograms/ml; range 0.49-1.09) were depressed (p less than 0.05). Conjugated dienes and glutathione peroxidase activity were in the normal range. In non-survivors (n = 5) initial levels of malondialdehyde and fluorescent products (median 11 versus 3.1 mumol/l; 74 versus 13% respectively) were higher than in survivors (p less than 0.05) and initial selenium levels were lower (median 0.58 versus 0.92 micrograms/l; p less than 0.05). These results are consistent with the concept that an oxidant/antioxidant imbalance--as indicated by elevated plasma lipid peroxides and depressed antioxidants--is involved in human septic shock and a fatal outcome.

Adult↗

Maldistribution of heterogeneous coronary blood flow during canine endotoxin shock.

STUDY OBJECTIVE - The aim was to investigate whether heterogeneous coronary blood flow is maldistributed during endotoxin shock. DESIGN - Variables were studied before (t = 0) and at t = 90 and t = 120 min after bolus injection of saline (n = 6) or endotoxin (n = 6). SUBJECTS - 12 anaesthetised mongrel dogs, weight 20-27 kg, were used. MEASUREMENTS AND MAIN RESULTS - We studied myocardial blood flows in small tissue sections (of about 1 g in left and 2 g in right ventricle) with radioactive microspheres, together with haemodynamic variables and global myocardial metabolism. At t = 0 min in controls, regional flows per 100 g were heterogeneous and ranged from a factor 0.2 to 2.7 and 0.6 to 1.6 of mean flow per 100 g to the left and right ventricle respectively; heterogeneity was unchanged at t = 90 and t = 120 min. Between t = 0, t = 90, and t = 120 min regional flows correlated: r = 0.78(SD 0.14), n = 18, for left ventricle, and r = 0.70(0.17) for right ventricle. In the endotoxin group, cardiac output and mean arterial pressure decreased by 44(7) and 48(11)% respectively, and lactate increased by 3.2(0.6) mmol.litre-1 at t = 120 min. Global left ventricle blood flow and delivery and metabolism of O2 were unchanged; lactate extraction and external work fell. The ratio between global right ventricular O2 delivery and external work also rose. Regional blood flows ranged from a factor 0.2 to 2.7 and 0.1 to 1.8 of mean flow to left and right ventricles respectively; heterogeneity did not differ from controls and did not change with time. Flow correlations with time were reduced: 0.45(0.24) for left ventricle and 0.45(0.26) for right ventricle (both n = 18, p less than 0.005 v controls). The left ventricular endocardial to epicardial flow ratio fell; flow was redistributed to both layers. CONCLUSIONS - Heterogeneous blood flow is redistributed throughout the heart during canine endotoxin shock so that, at unchanged global blood flow and flow heterogeneity, flow decreases in some but increases in other areas. Flow maldistribution may be associated with focal ischaemia, which may be masked by a rise in O2 uptake for a given workload (contractile inefficiency) in overperfused areas, and may thereby contribute to a fall in global myocardial external work for a given O2 delivery.

Animals↗

Adrenocortical insufficiency: a rare presentation of non-Hodgkin's lymphoma.

A 77-year-old man presented with adrenocortical insufficiency, for which a cause could not be identified during life. Six weeks after the diagnosis, the patient died, while receiving adequate cortisol therapy, from a fulminant gastrointestinal bleeding. A pleural effusion, found shortly before death, later showed malignant lymphoid cells. At autopsy, a widely spread, diffuse, malignant B-cell lymphoma with destruction of, amongst others, both adrenals was found. The retroperitoneal, but not the peripheral lymph nodes were involved, thereby explaining failure of diagnosis while the patient was living. This is the first description of a diffuse B-cell Non-Hodgkin's lymphoma presenting with adrenocortical insufficiency. Potentially curable malignant invasion of the adrenals can present with adrenocortical insufficiency, and may thus justify imaging of the adrenals with sensitive techniques in elderly patients with unexplained primary adrenocortical insufficiency.

Adrenal Cortex Diseases↗

Acute renal failure in the medical intensive care unit: predisposing, complicating factors and outcome.

The factors predisposing to and complicating acute renal failure (ARF) in the medical intensive care unit (ICU), and their relative influence on outcome during ARF are unclear. We retrospectively evaluated the relative importance of age, prior chronic disease (including chronic renal failure), sepsis and organ system failure, for development and outcome of ARF in the medical ICU. Of 487 consecutively admitted patients, 78 (16%) had ARF, in 63% treated with renal replacement therapy. Mortality was 63%. Independently from each other, advancing age, prior chronic disease, and cardiovascular and pulmonary failure directly related to the development of ARF, while neurological failure related inversely. Sepsis only contributed to ARF prediction from these variables if cardiopulmonary failure was excluded. Advancing age, cardiovascular failure before and after onset of ARF, pulmonary failure before ARF and use of renal replacement therapy were the major independent factors directly related to ARF mortality, while prior chronic renal failure related inversely and sepsis did not contribute. Hence, the outcome of ARF in a medical ICU is largely dependent on factors predisposing to ARF, even though the severity and complications of ARF may partly contribute. Our results may help in deciding on the prevention and therapy of ARF in a medical ICU.

Acute Kidney Injury↗

Total body blood volume redistribution in porcine E. coli septic shock: effect of volume loading, dobutamine, and norepinephrine.

The purpose of the present study was to determine the effect of volume loading alone (CONTR) vs. volume loading in combination with dobutamine (DOBU) or norepinephrine (NOR) on total body blood volume distribution in septic shock. After instrumentation, injection of in vitro labelled 99mTc red blood cells, and baseline measurements, anesthetized, ventilated pigs (n = 21) received 3-4.10(8).kg-1 live E. coli bacteria intravenously. Images of thorax, abdomen, and hindlimb were obtained by using a gamma camera simultaneously with hemodynamic measurements. E. coli infusion resulted in a decrease in arterial pressure, ventricular filling pressures, and cardiac output with a concomitant increase in pulmonary arterial pressure. Blood volume was redistributed from the heart, lungs, spleen, abdomen, and leg to the liver. After randomization, the CONTR group (I, n = 5) was subjected to volume loading, and treatment groups (each n = 8) received volume loading in combination with DOBU (group II, 5-10 micrograms/kg/min) or NOR (group III, 0.25-0.50 micrograms/kg/min). As compared to volume loading alone, DOBU and NOR increased cardiac output but only NOR restored arterial pressure. Volume loading increased blood volume in all regions studied; however, it was unequally distributed amongst organs with a preference for the liver. Neither DOBU nor NOR influenced the partitioning of the infused volume between organs. However, NOR prevented pooling of blood in the leg.

Animals↗

Arterial and mixed venous blood acid-base balance during hypoperfusion with incremental positive end-expiratory pressure in the pig.

The authors sought to determine how hypoperfusion influences acid-base balance in arterial and mixed venous blood. In anesthetized, ventilated pigs (n = 12), we determined hemodynamics, O2 uptake, CO2 output, dead-space ventilation, arterial and mixed venous blood acid-base balances, and lactate concentrations during graded reductions in cardiac output by incremental positive end-expiratory pressure (PEEP, 0-20 cm H2O). Cardiac output decreased from 3.2 +/- 0.2 (mean +/- SEM) to 1.2 +/- 0.1 L/min at 20 cm H2O PEEP. Oxygen delivery declined more than O2 uptake did by 60% +/- 2% and 27% +/- 2%, respectively. The decrease in CO2 output (by 21% +/- 2%) was less than that in O2 uptake. Fractional dead-space ventilation increased. At a slight increase in carbon dioxide tension (PCO2) of 4 +/- 1 mm Hg, pH decreased in arterial blood from 7.54 +/- 0.01 to 7.47 +/- 0.02 mmol/L, and standard bicarbonate decreased from 30.3 +/- 0.5 to 27.5 +/- 0.6 mmol/L. The decrease in standard bicarbonate exceeded the increase in blood lactate concentrations. At a similar decrease in standard bicarbonate, the decrease in pH was larger (P less than 0.005) in mixed venous blood than in arterial blood owing to a larger increase in PCO2 (from 40 +/- 2 to 50 +/- 2 mm Hg, P less than 0.005). The changes were reversed after discontinuing PEEP. The authors conclude that ischemia after incremental PEEP results in tissue metabolic acidosis with superimposed respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

The haemodynamics of septic shock.

Both peripheral vascular abnormalities and changes in myocardial function are hallmarks of septic shock. Their complex interactions result in inadequate and maldistributed microcirculatory flow and progressive organ dysfunction. Inappropriate vasodilation, microembolization and endothelial cell injury are proposed mechanisms that may induce maldistribution of flow in the microcirculation and inefficient, defective peripheral oxygen extraction. Abnormal myocardial function is manifested by diminished right and left ventricular ejection fractions, ventricular dilatation, altered Frank-Starling curves and diastolic pressure-volume relationships. These changes are already observed in an early stage of septic shock and are entirely reversible in survivors.

Blood Circulation↗

Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit.

We retrospectively studied relations between age, pre-existing chronic disease, sepsis, organ system failure, and mortality in 487 patients from a medical ICU. Single organ system failure (SOSF) occurred in 136 (28%) and multiple (greater than or equal to 2) organ system failure (MOSF) in 187 (38%) patients. Cardiovascular and pulmonary failure predominated. Overall mortality was 27%. SOSF mortality was 16% and for MOSF 58%. Eighty-three percent of nonsurvivors had MOSF. Hence, MOSF is common and a major cause of death in critically ill medical patients. Advancing age and prior chronic disease may diminish physiologic reserve and predispose to sepsis and MOSF. Although sepsis is a major risk factor for MOSF, a nonspecific host response to critical illness may contribute to the syndrome in 35% of patients. Advancing age, chronic disease, and the number of failing organs, particularly failure of cardiovascular, pulmonary, renal, and neurologic systems, are major determinants of overall mortality, but sepsis is not an independent contributor.

Adolescent↗

Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock.

We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gammacamera and a computer until 5 hours after baseline. Regions of interest were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C (P less than .05 vs. lung), confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C (rs = 0.94, P less than .05) and T (rs = 0.89, P = .05) but not in N (rs = -0.37, n.s.). We conclude that neither N nor T treatment beneficially influences the course of septic shock in pigs. Although neither drug combats noninvasively assessed regional microvascular albumin leakage and formation of albumin-rich ascites, N may ameliorate increased pulmonary microvascular permeability as judged from post mortem data.

Animals↗

Decreased reflection coefficient as a possible cause of low blood pressure in severe septicaemia.

A 44-year-old woman developed a septicaemia with low intra-arterially recorded blood pressure values despite vasoactive medication and optimal support. Sphygmomanometer cuff measurements showed higher values than intra-arterial blood pressure records. We suggest a low reflection coefficient of the capillary bed as the cause of this phenomenon. The constant pressure of the sphygmomanometer cuff on the venous tract appeared to create an increase of the reflection coefficient in our patient, thus causing higher blood pressure readings with the sphygmomanometer cuff measurements than expected.

Adult↗