PubMed Health⌕ Search

Biomedical subjects

J P Mallie

Publications and source records attributed to J P Mallie.

At least 19 recordsLinked to original sources
PubMed2001

Tonicity balance, and not electrolyte-free water calculations, more accurately guides therapy for acute changes in natremia.

The usual way to decide why hyponatremia or hypernatremia has developed and to plan goals for its therapy is to analyze events in electrolyte-free water (EFW) terms. We shall demonstrate that an EFW balance does not supply this information. Rather, one must calculate mass balances for water and sodium plus potassium separately (a tonicity balance) to understand the basis for the change in natremia and the proper goals for its therapy. These points are illustrated with a clinical example.

Adolescent↗
PubMed1999

Comparison of systemic and regional effects of dobutamine and dopexamine in norepinephrine-treated septic shock.

OBJECTIVES: To compare the effects of dobutamine and dopexamine on systemic hemodynamics, lactate metabolism, renal function and the intramucosal-arterial PCO(2) gap in norepinephrine-treated septic shock. DESIGN: A prospective, interventional, randomized clinical trial. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: After volume resuscitation, 24 patients were treated with norepinephrine alone titrated to obtain a mean arterial pressure of 75 mmHg and a cardiac index greater than 3. 5 l/min(-1). m(-2). INTERVENTIONS: Patients were randomized to receive an infusion of dobutamine (n = 12) (5 microg/kg per min) or dopexamine (n = 12) (1 microg/kg per min). MEASUREMENTS AND MAIN RESULTS: Baseline measurements included: hemodynamic parameters, renal parameters (diuresis, creatinine clearance and urinary sodium excretion), gastric mucosal-arterial PCO(2) gap, arterial and mixed venous gases and arterial lactate and pyruvate levels. These measurements were repeated after 1 (H(1)), 4 (H(4)) and 24 (H(24)) h. No difference was found between dobutamine and dopexamine among H(0) and H(1), H(4) and H(24) values for hemodynamics. Dobutamine and dopexamine at low doses had no significant effect on mean arterial pressure, heart rate, cardiac index, oxygen delivery, oxygen consumption and pulmonary artery occlusion pressure. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. After 4 and 24 h lactate concentration decreased in the dobutamine group from 2.4 +/- 1 mmol/l to 1.7 +/- 0. 7 mmol/l and 1.5 +/- 0.4 mmol/l, respectively, while it increased in the dopexamine group from 2.3 +/- 1 mmol/l to 2.7 +/- 1 mmol/l after 4 h and returned to baseline values after 24 h (2.2 +/- 0.6). After 24 h the lactate/pyruvate ratio decreased in the dobutamine group from 15 +/- 5 to 12 +/- 3 (p < 0.05) while it was unchanged in the dopexamine group (from 16 +/- 6 to 17 +/- 4). Arterial pH increased in the dobutamine group from 7.35 +/- 0.05 to 7.38 +/- 0.07 (p < 0. 05) while it was unchanged in the dopexamine group (from 7.34 +/- 0. 01 to 7.35 +/- 0.10). The PCO(2) gap decreased after 1 and 4 h in both the dobutamine and dopexamine groups (p < 0.05 with respect to baseline). When looking at individual responses, however, patients from both groups exhibited an increased gastric PCO(2) gap. No difference was found between dobutamine and dopexamine for renal parameters. CONCLUSIONS: In norepinephrine-treated septic shock, low doses of neither dobutamine nor dopexamine caused significant effects on systemic hemodynamics and renal function and both dobutamine and dopexamine inconsistently improved the PCO(2) gap. The present results support the need for individual measurement of the effects of catecholamine on the PCO(2) gap.

Analysis of Variance↗
PubMed1999

Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, on lactate metabolism and muscle high energy phosphates during endotoxic shock in rats.

Overproduction of NO by an inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. In such situations, NOS inhibition might be of therapeutic value, although detrimental side effects possibly related to inhibition of constitutive NOS have been reported. The use of L-canavanine, a selective inhibitor of iNOS, might be more suitable. The aim of the study was to compare in a rodent endotoxic shock the effects of saline (2 mL/h), N(G)-methyl-L-arginine(L-NMMA) (10 mg/kg/h) and L-canavanine (100 mg/kg/h) on muscle intracellular pH (pHi) and intracellular bioenergetic patterns (ATP, phosphocreatine/inorganic phosphate ratio) using in vivo 31P magnetic resonance spectroscopy (31P MRS). Three groups of anesthetized, mechanically ventilated and paralyzed rats received an intravenous infusion of 15 mg/kg of endotoxin. A fourth time-matched control group (n = 8) received 2 mL/h of saline. Mean arterial pressure, femoral blood flow, arterial blood gases, lactate, nitrate level, and 31P nuclear magnetic resonance (31P MRS) measurements were acquired at onset (T = 0), 90 min (T = 90), and 180 min (T180) after the endotoxin challenge. Femoral oxygen delivery was calculated as the product of femoral blood flow (mL/min) and arterial oxygen content. Endotoxin induced a marked decrease in arterial pressure and femoral oxygen delivery and an increase in lactate level. Intracellular pH and phosphocreatine/inorganic phosphate ratio decreased. ATP level did not change. Both L-NMMA and L-canavanine reversed the endotoxin-induced decrease in arterial pressure. L-NMMA attenuated the decrease in femoral oxygen delivery and the increase in lactate level while these were corrected by L-canavanine. Considering 31P MRS derived bioenergetic indices, the endotoxin-induced decrease in pHi and Pcr/Pi was attenuated by L-NMMA and corrected by L-canavanine. In conclusion, in a rodent model of endotoxinic shock, the continuous infusion of L-canavanine, a selective iNOS inhibitor, improved the systemic hemodynamic parameters and the intracellular bio-energetic patterns estimated by in vivo 31P MRS. To the contrary, the continuous infusion of both constitutive and inducible NOS inhibitor L-NMMA was not followed by the same achievement.

Adenosine Triphosphate↗
PubMed1998

Acute hyponatremia in the perioperative period: insights into its pathophysiology and recommendations for management.

Our purpose is to review the topic of acute postoperative hyponatremia by focusing on pertinent aspects of the physiology of water and solute excretion. Four areas will be highlighted: an examination of the source of addition of electrolyte-free water, an exploration of the basis for the very large natriuresis that occurs during cerebral salt wasting following neurosurgery, possible reasons to explain why acute postoperative hyponatremia may pose a greater risk for young women [Ayus and Arieff 1996, Ayus et al. 1992, Arieff 1986, Wijdick et al. 1991], and issues related to treatment of acute hyponatremia.

Acute Disease↗
PubMed1997

Effective water clearance and tonicity balance: the excretion of water revisited.

OBJECTIVE: To demonstrate (1) that hyponatremia is usually due to an inappropriately low rate of excretion of electrolyte-free water and (2) that the measure "effective water clearance" (EWC) provides better information about renal defence of the body tonicity than does the classic measure free-water clearance, and to provide the rationale for calculating a "tonicity balance," which involves using water and sodium plus potassium intakes and their renal excretion to reveal the basis for changes in body tonicity. DESIGN: Prospective study. PARTICIPANTS: Four normal subjects with no conditions affecting excretion, 10 patients with advanced congestive heart failure (CHF) and 5 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). INTERVENTION: Normals and patients were administered a standard water load (20 mL per kg of body weight) during 45 minutes, and blood and urine samples were taken before, during and after the load was given. MAIN OUTCOME MEASURES: Urine and blood sodium and potassium concentrations, osmolar clearance, free-water clearance, electrolyte clearance and EWC. RESULTS: The water load was excreted rapidly by normals, more slowly by patients with CHF, and not at all by patients with SIADH. The EWC was positive in normals and those with CHF, but negative in those with SIADH. In patients with CHF, the EWC, but not the free-water clearance, helped explain why hyponatremia was corrected after the water load was given. CONCLUSIONS: In subjects with abnormal water excretion, the EWC provides the physiologic explanation for the renal role in variations in natremia. The authors propose a bedside evaluation of renal water and electrolyte handling that takes into consideration the role of urinary potassium in body tonicity. Changes in body tonicity can be explained by a "tonicity balance," a calculation in which the source and the net balance of sodium, potassium and water are considered.

Electrolytes↗
PubMed1996

Functional renal maturation in rat neonates after prenatal exposure to furosemide.

We investigated the pattern of functional renal maturation and electrolyte handling on postnatal day 1, (PD1), day 5 (PD5), and day 12 (PD12) in rat neonates, after mothers were given furosemide during pregnancy. The drug was administered (75 mg/kg per day i.p.) on day 7-11 (organogenesis) and 14-18 (nephrogenesis) of gestation. On PD1 and PD5, there was a disturbance of the urinary concentrating ability with a hyperdiuresis and an over-stimulated ionic exchange, mainly the distal sodium reabsorption. From PD1 to PD12, a progressive functional recovery in electrolyte handling appeared. However, on PD12, when nephrogenesis was achieved, the renal concentrating defect remained. We discuss the possibility of a drug-induced delay in the development of the loop of Henle, leading to functional and morphological adaptations of already developed parts of the nephron.

Animals↗
PubMed1996

What is the impact of potassium excretion on the intracellular fluid volume: importance of urine anions.

Hyponatremia is a common electrolyte abnormality that causes symptoms as a result of swelling of brain cells. We evaluated the impact of a negative balance for sodium (Na) and potassium (K) salts on the intracellular fluid (ICF) volume, emphasizing the role of anions excreted with K. Rats (N = 10) were deprived of food and water for 24 hours. They received half-isotonic saline to expand their extracellular fluid (ECF) volume by 20%; a long acting antidiuretic hormone (DDAVP) preparation was given to prevent the excretion of electrolyte-free water. The concentration of Na in plasma fell from 139 +/- 1 mM to 120 +/- 2 mM 24 hours after the infusion of hypotonic saline (P < 0.01). Since these rats had a small negative balance for water (4 +/- 1 ml), hyponatremia was due to their negative balances for Na (2.2 +/- 0.3 mmol) and K (2.2 +/- 0.1). There were negative balances for Cl (2.4 +/- 0.2 mmol) and phosphate (0.7 +/- 0.05 mmol). Despite the negative balance for NaCl, the ECF volume as assessed by 3H-inulin space was not contracted. In this model for acute hyponatremia, its basis was electrolyte loss, but the ECF volume was not contracted, suggesting that water shifted from the ICF to the ECF. Hyponatremia is associated with cell swelling only if its cause is positive water balance and/or is loss of Na from the ECF. It is critical to examine the urine anions to determine the compartment of origin of particles excreted with K and thereby whether hyponatremia will result in overall expansion or contraction of the ICF volume.

Animals↗
PubMed1996

Urea recycling: an aid to the excretion of potassium during antidiuresis.

Urea absorption in the inner medullary collecting duct provides a mechanism to elevate the concentration of urea in the papillary interstitial fluid and thereby permit the excretion of urea with as little water as possible. Urea reabsorption may have another important effect - to aid in the excretion of potassium (K). K excretion depends on two processes: first, factors such as aldosterone which cause the concentration of K in the luminal fluid of the cortical distal nephron to be high and, second, factors which augment the flow rate through those nephron segments. Since, the osmolality of the luminal fluid in the cortical collecting duct (CCD) and plasma are equal when antidiuretic hormone acts, the flow rate in the CCD is dependent on solute delivery. Urea is a major solute in the lumen of the CCD and thereby plays an important role in maintaining the CCD flow rate. Since urea and K are often found in the same foods, having urea help the excretion of K is potentially advantageous. If the excretion of urea was low, the flow rate in the terminal CCD would decline. In this circumstance, the luminal K concentration would have to rise in proportion to the fall in flow rate or there would be a diminished rate of excretion of K and, possibly, hyperkalemia.

Animals↗
PubMed1994

Effects of sodium bicarbonate on striated muscle metabolism and intracellular pH during endotoxic shock.

The effects of HCO3Na load on acid-base balance and muscle intracellular bioenergetics have been investigated using 31P-magnetic resonance spectroscopy in an experimental model of endotoxinic shock. Anesthetized, mechanically ventilated, and paralyzed rats (n = 16) were given an intravenous bolus of Escherichia coli lipopolysaccharide (15 mg/kg). When shock was established they were randomly assigned to receive either HCO3Na intravenously (2 mmol/kg in 2 min) or an equimolar saline injection. Lipopolysaccharide induced a significant decrease in the levels of mean arterial pressure (58 +/- 6 vs. 120 +/- 8 mmHg), arterial pH (7.20 +/- .03 vs. 7.35 +/- .01), intracellular pH (6.86 +/- .04 vs. 7.08 +/- .01), a marked hyperlactatemia (7 +/- 3 vs. 1.2 +/- .2 mmol/L) and a drop in the phosphocreatine-inorganic phosphate ratio. In the bicarbonate-loaded rats, mean arterial pressure further decreased whereas it remained unchanged in the saline group. Bicarbonate increased arterial pH and PaCO2 transiently. In the saline group, arterial pH decreased and PaCO2 remained stable. In both groups, intracellular pH and high energy phosphates had a similar evolution. In this model of septic shock, partial correction of arterial pH using HCO3Na did not reduce the metabolic cellular injury in skeletal muscle. Based on these results, HCO3Na may be of limited therapeutic value in severe septic metabolic acidosis.

Acidosis, Lactic↗
PubMed1993

Abnormalities in histamine pharmacodynamics in chronic urticaria.

Histamine plays a key role in the pathogenesis of chronic urticaria (CU). The authors of this paper have studied the effects of ingested histamine in 25 patients with CU. A 120 mg dose of histamine, well-tolerated in the healthy subject, was instillated into the duodenum. Concomitantly, plasma histamine (H) levels and plasma and urinary methylhistamine (MH) levels were measured. Intraduodenal administration of histamine was responsible for the development of an attack of urticaria in 64% of patients, while control subjects were asymptomatic. Plasma histamine levels were significantly higher after digestive histamine challenge (DHC) in patients with CU compared with controls. An abnormal increase in plasma histamine was observed in 72% of them. Plasma MH exhibited the same kinetic behaviour with a usually delayed time-pattern. Urinary MH concentration was higher in patients presenting with early-onset urticaria during the first hour than in those with the late-onset type between 1 and 12 hr after DHC. The coefficient of methylation (plasma MH/MH+H) was not significantly different in patients presenting with an attack of urticaria following DHC and in other subjects. Urinary excretion of MH and urinary flow increased significantly in patients presenting with an attack of urticaria following DHC which corresponds to increased absorption of histamine during the 5-hr period following DHC and its role on excretion by the kidney via vasodilation which it induces. This study demonstrates the abnormal frequency of disturbances in the metabolism of exogenous histamine in patients with CU. Increased plasma H accounts for the abnormal passage of H across the intestinal barrier which can result either from intestinal hyperpermeability and/or a deficit in the enzymatic catabolism of histamine. The systems of methylation and urinary clearance of MH appear to be effective. It is thus postulated that there is a deficit in diamine oxidase (DAO) in the enterocyte. The lack of correlation between the kinetic behaviour of plasma H and the onset of urticaria draws attention to the extent of individual variability in skin reactivity to histamine.

Administration, Oral↗
PubMed1993

Gentamicin administered during gestation alters glomerular basement membrane development.

Gentamicin during gestation alters glomerular basement membrane development. A drug-induced nephrotoxicity was described for neonates after gentamicin was given intraperitoneally to pregnant Wistar rats; glomerular alterations and changes in permselectivity were important. We investigated the ultrastructure of the glomerular basement membrane (GBM), the arrangement of anionic sites, and the urinary proteins at two ages, with 1-day- and 12-month-old control and prenatally exposed animals. For neonates, the pattern of glomerular differentiation was similar, anionic sites were made of heparan sulfate proteoglycans, and the GBM had the same total thickness in both groups. After transplacental gentamicin exposure, the lamina densa was larger; the laminae rarae were thinner; the density of anionic sites was increased; the levels of hydroxyproline, sulfate, and hexuronic acid in the kidney were increased; and the immunoelectrophoresis of urinary proteins was abnormal. For adults, prenatal exposure to gentamicin led to altered juxta-medullary glomeruli with a larger GBM and abundant anionic sites, especially in the lamina densa, and to a protein excretion different from that of controls. Thus, gentamicin administered during pregnancy leads to permanent alterations of the GBM with modifications of both the layers and the anionic sites, possibly because of a perturbed protein metabolism. These altered glomeruli are at risk during life and could be the starting point for a kidney disease.

Animals↗
PubMed1993

Effect of chronic potassium depletion on muscle bioenergetics in rats.

To test the hypothesis of muscle bioenergetic impairment in potassium depletion, chronic potassium-depleted rats and pair-fed control rats were studied with phosphorus 31 nuclear magnetic resonance measurements of leg muscle intracellular pH, phosphocreatine, inorganic phosphate, and adenosine triphosphate at rest and during maximal nontetanic stimulation, 48 hours after a swimming test. The potassium-depleted rats exhibited a significant hypokalemia, a metabolic extracellular alkalosis, and an intracellular acidosis. Their physical endurance was markedly reduced, and they displayed higher plasma creatine kinase levels than the control group. However, the phosphocreatine/inorganic phosphate ratio, which is a measure of the energy reserve of the cell, was similar in both groups at rest and during electrical stimulation and subsequent recovery. Resting muscle glycogen and relative intracellular acidification during stimulation did not differ in the two groups, arguing against an impairment of anaerobic metabolism in potassium depletion. These results indicate that the energy availability of muscle cell is unchanged during potassium deficiency.

Animals↗
PubMed1992

Respective effects of malnutrition and phosphate depletion on endurance swimming and muscle metabolism in rats.

To examine the respective roles of malnutrition and phosphate depletion on muscle exercise capacity and bioenergetics, phosphate-depleted, either underfed or partly refed rats; phosphate-supplemented, either underfed or partly refed rats; and well-nourished control animals were studied, using swim time to exhaustion and 31P NMR spectroscopy measurements of muscle phosphocreatine, inorganic phosphate, adenosine triphosphate and intracellular pH. Only partly refed rats displayed hypophosphataemia. Swim time to exhaustion was lower in non-refed rats than in controls. Among the four groups, both refeeding and phosphate depletion positively affected swim time to exhaustion (both with P less than 0.02), and swim time to exhaustion was negatively correlated with phosphataemia (P less than 0.05). At rest, the ratio of muscle phosphocreatine/inorganic phosphate was lower in the phosphate-supplemented rats than in controls, whereas muscle phosphocreatine/adenosine triphosphate and intracellular pH were comparable. After non-tetanic stimulation, the muscle phosphocreatine recovery was slower in the four groups than in controls and closely correlated with exhaustion (P less than 0.01). These findings suggest that malnutrition alters the capacity of muscular work, mainly because of a reduced cell oxidative energy availability. These patterns are improved by partial refeeding and clearly influenced by the level of phosphorus intake, whether depletion is capable of improving metabolic alterations or uncontrolled supplementation is deleterious in malnourished animals.

Animals↗
PubMed1991

Glomerular alterations in rat neonates after transplacental exposure to gentamicin.

Alterations of tubules and glomerules have been reported previously in kidneys of rat neonates after aminoglycosides were given to the mother during gestation. Here, we have studied the effects of gentamicin on the development of the glomerular basement membrane (GBM). Pregnant Wistar female rates were treated with gentamicin. Deliveries occurred normally. Using electron microscopy, we looked at the deepest glomerules of the kidneys of 1-day-old neonates: myeloid bodies were found in podocytes, and the GBM appeared thicker and denser than in controls. Anionic ferritin, injected intravenously crossed the GBM in prenatally gentamicin-exposed animals, but not in controls. Furthermore, urine electrophoresis showed the presence of proteins normally found only in the urine of fetuses 2 days before birth. We suggest then, that in utero exposure to gentamicin leads to a delay of renal maturation and that the GBM is altered in juxtamedullary nephrons while it is normally differentiated and functioning in controls. Thus exposure to drugs before birth could be harmful to the GBM.

Abnormalities, Drug-Induced↗
PubMed1989

[Treatment of severe hyponatremia by restricted water intake].

The outcomes of 23 patients admitted to a medical intensive care unit for severe hyponatraemia (less than 120 mEq/l) associated with neurological disorders were reviewed. All patients had restricted water intake combined with a sodium intake adjusted to the natriuresis, and some received a loop diuretic. The mean correction rate during the first 48 hours was slow (greater than 12 mmol/l.24 h) in 16 cases and fast (less than or equal to 12 mmol/l.24 h) in 7 cases. Following biochemical cure, 2 patients in the fast correction group had an unfavourable outcome: one died for an unknown reason, the other developed pontine myelinosis. A review of the literature did not provide evidence that a certain rate of correction was better than the other, but it showed that an excessive rise in natraemia or an overcorrection of hyponatraemia was dangerous. Slow correction of hyponatraemia, usually obtained with water intake restriction, may be recommended.

Adult↗
PubMed1989

[Experimental study of nephrotoxicity: effects, on the newborn rat kidney, of aminoglycoside administration during gestation].

Treatment of the pregnant rat with aminoglycosides provokes nephrotoxicity in the newborn. This study compares the effects of three antibiotics belonging to this group: gentamicin (same day dose administered in one or two injections according to the groups), sisomicin and dibekacin, all administered during the last phase of gestation. Newborns were tested the day after birth, creatinine clearance was measured and then the kidneys were removed for histopathological examination. Functional variations (diuresis, creatinine clearance) and histological alterations of glomerula and tubules were observed. Slight differences suggest that, depending on the antibiotic used, intra-cellular nephrotoxic mechanisms are not completely identical. The modifications which occur after the administration of aminoglycosides, lead us to believe that further studies on the possible fetal nephrotoxic effects of drugs taken by mothers during gestation should be undertaken.

Animals↗
PubMed1985

Does the in-utero exposure to furosemide delay the renal maturation?

Two groups of pregnant Wistar rats were constituted, one treated with Furosemide IP and one with saline. The drug was given on days 7-11 and 14-18 of the pregnancy. Litters from the two groups were not different in number of pups, body weight, and/or kidney weight, but exposed in-utero neonates, studied shortly after birth, exhibited a significant lower number of differentiated glomeruli than those of the control group. As well as the difficulty of explaining this phenomenon, this condition raises the problem of a possible compensation by the postnatal nephrogenesis, which is important in the rat, and leads to the question of what will be the total amount of nephrons for the adult life in species with or without complete in utero nephrogenesis.

Animals↗