Extreme hyponatremia of 87 mmol/l without neurologic complications in a severely hypovolemic patient.
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Acid-Base Imbalance↗
Biomedical subjects
M Emmett
Publications and source records attributed to M Emmett.
Michael Emmett, MD, MACP: a conversation with the editor. Interview by William Clifford Roberts.
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Interview↗
Effect of mineralocorticoid activity on transtubular potassium gradient, urinary [K]/[Na] ratio, and fractional excretion of potassium.
Clinical assessment of potassium derangements may require evaluation of mineralocorticoid status. Several indirect indices of mineralocorticoid activity based on renal electrolyte excretion have been proposed and include the transtubular potassium gradient, urinary [K]/[Na] ratio, and renal fractional excretion of potassium. We studied the impact of high mineralocorticoid activity versus blocked mineralocorticoid activity on these indices in otherwise normal subjects who ingested a defined diet. Eight normal subjects received either fludrocortisone or spironolactone for 4 days. After a washout period of > or = 2 weeks, each subject then received the opposite regimen. Subjects ingested an identical high-potassium diet during both experimental periods. The renal fractional excretion of potassium and transtubular potassium gradient were calculated using standard formulas. Fludrocortisone caused an increase in body weight and no significant reduction in serum potassium concentration, while spironolactone decreased body weight and increased plasma potassium concentration. After 1 or 2 days of treatment with fludrocortisone, the average values for all urinary indices of mineralocorticoid activity were significantly higher than after 1 or 2 days of treatment with spironolactone. However, the differences between these indices in the fludrocortisone and spironolactone test periods diminished by day 3 and were nonexistent by day 4. In conclusion, the transtubular potassium gradient, [K]/[Na] ratio, and renal fractional excretion of potassium reflect acute changes in mineralocorticoid activity. However, these indices do not discriminate between states of high and low mineralocorticoid activity lasting longer than 2 to 3 days.
Cross-Over Studies↗
Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease.
Hyperkalemia in patients with renal failure is frequently treated with a cation exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in combination with a cathartic, but the effect of such therapy on serum potassium concentration has not been established. This study evaluates the effect of four single-dose resin-cathartic regimens and placebo on 5 different test days in six patients with chronic renal failure. Dietary intake was controlled. Fecal potassium output and serum potassium concentration were measured for 12 h. Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The addition of resin caused an increase in insoluble potassium output but a decrease in soluble potassium output; therefore, there was no significant effect of resin on total potassium output. Sorbitol plus resin caused less potassium output than phenolphthalein plus resin. On placebo therapy, the average serum potassium concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This rise was apparently abrogated by some of the regimens that included resin; this may have been due in part to extracellular volume expansion caused by absorption of sodium released from resin. Phenolphthalein regimens were associated with a slight rise in serum potassium concentrations (similar to placebo); this may have been due to extracellular volume contraction produced by high volume and sodium-rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens reduced serum potassium concentrations, compared with baseline levels. Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes.
Analysis of Variance↗
Metformin-associated lactic acidosis.
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Acidosis, Lactic↗
Effect of three laxatives and a cation exchange resin on fecal sodium and potassium excretion.
BACKGROUND/AIMS: The treatment of hyperkalemia in patients with renal insufficiency often includes the ingestion of sorbitol and a cation exchange resin. Sorbitol alone may be used to remove sodium and water from overloaded patients. The efficacy of these regimens has never been compared with other laxative or laxative-resin combinations. The aim of the study was to compare the relative effect of three laxatives with different mechanisms of action, alone and in combination with resin, on fecal sodium and potassium excretion. METHODS: Sodium, potassium, and water excretion in 12-hour stool collections were analyzed after various laxative-resin combinations in normal subjects. RESULTS: Correctol (yellow phenolphthalein) (Schering Plough Health Care Products, Memphis, TN) was more effective than sorbitol or sodium sulfate in causing fecal sodium and potassium loss. Resin recovery in stool was much greater with phenolphthalein than with other laxatives, and more potassium was excreted in stool with phenolphthalein-resin than with phenolphthalein alone or other laxative-resin combinations. Sorbitol caused more undesirable gastrointestinal symptoms than did sodium sulfate or phenolphthalein. CONCLUSIONS: In normal people, phenolphthalein (1) is preferable to other laxatives in causing fecal sodium and potassium excretion, (2) hastens resin transit through the intestine compared with other laxatives, and (3) produces greater fecal potassium excretion when combined with resin than phenolphthalein alone or other laxative-resin combinations.
Cathartics↗
The post-transurethral resection of prostate syndrome: therapeutic proposals.
Absorption of large volumes of irrigation fluid during transurethral resection of the prostate (TURP) can produce hyponatremia, coma, blindness, and cardiorespiratory depression. This has been termed the "post-TURP syndrome." The pathophysiology and management of this syndrome are controversial. A case of severe post-TURP syndrome due to the absorption of hypotonic glycine irrigant is reported. This patient developed severe hyponatremia, slight hypo-osmolality, hyperglycinemia, hyperserinemia, hyperammonemia, and hypocalcemia. He became comatose, profoundly hypotensive, bradycardic, and transiently blind. Because of this combination of severe biochemical, neurologic, and hemodynamic abnormalities, we elected to treat this patient with hemodialysis. The biochemical and clinical manifestations resolved completely. The pathophysiology and treatment of this disorder are discussed and a role for hemodialysis is suggested.
Aged↗
Can maintenance cyclosporine be used in psoriasis without decreasing renal function?
Nephrotoxicity attributable to cyclosporine therapy is dose dependent and unlikely to occur in psoriasis treatment protocols using less than 5 mg/kg/d in otherwise healthy patients. Any long-term or maintenance protocol should include regular monitoring of urea nitrogen/creatinine levels and blood pressure. Cyclosporine is a potent drug, and it is reasonable to monitor its administration to otherwise healthy psoriasis patients with yearly measurement of glomerular filtration rate (GFR), especially in elderly patients or patients with diminished renal reserve (eg, diabetes). There is no convincing evidence of irreversible renal dysfunction in psoriasis patients on low-dose cyclosporine protocols, nor is there evidence that cyclosporine in low doses in completely safe or banal. Therefore, we suggest monitoring GFR at 3, 6, and 12 months after initiating therapy, provided serum creatinine level is stable. If serum creatinine level increases by > 30% over baseline, GFR should be monitored more frequently and the dose of cyclosporine adjusted if there is a persistent decrease.
Cyclosporine↗
Calcium acetate control of serum phosphorus in hemodialysis patients.
Calcium acetate has many characteristics of an ideal phosphorus binder. It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above. One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate. We studied chronic (3-month) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers. All phosphorus binders were stopped for 2 weeks. Calcium acetate at an initial dose of 8.11 mmol (325 mg Ca2+) per meal was then used as the only phosphorus binder. Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L (5.5 mg/100 mL). Final calcium acetate dose was 14.6 mmol (586 mg) Ca2+ per meal. Sixteen patients developed mild transient hypercalcemia (mean, 2.84 mmol/L [11.4 mg/dL]. Initial phosphorus values in mmol/L (mg/dL) were 2.39 (7.4); at 1 month, 1.91 (5.9); and at 3 months, 1.68 (5.2). Initial calcium values in mmol/L (mg/dL) were 2.22 (8.9); at 1 month, 2.37 (9.5); and at 3 months, 2.42 (9.7). Initial aluminum values in mumol/L (micrograms/L) were 2.99 (80.7); and at 3 months were 2.54 (68.4). Initial C-terminal parathyroid hormone (C-PTH) values in ng/mL were 14.6; at 1 month, 11.9; and at 3 months, 13.2. Sixty-nine patients then entered a double-blind study. Phosphorus binders were stopped for 1 week. Calcium acetate (at a dose established in a prior study) or placebo was then administered for 2 weeks. Next, patients were crossed to the opposite regimen for 2 weeks. Initial phosphorus was 2.36 mmol/L (7.3 mg/100 mL) and calcium 2.22 mmol/L (8.9 mg/100 mL).(ABSTRACT TRUNCATED AT 250 WORDS)
Acetates↗
Reperfusion of ischemic skeletal muscle causes erythrocyte hemolysis and decreases subsequent oxidant-mediated lung injury.
A prior transient hindlimb ischemia/reperfusion (I/R) insult decreased acute lung injury in rats subsequently treated with cobra venom factor. I/R-mediated protection was associated with erythrocyte hemolysis, increased plasma catalase activity, and increased plasma hydrogen peroxide scavenging activity. In contrast, hindlimb I/R did not increase lung catalase activity, and large amounts of injected catalase were required to increase lung catalase activity. The results suggest that limited I/R in one organ can induce systemic processes that may decrease a subsequent O2 metabolite-mediated injury in another distant organ. The mechanism may involve release of catalase from hemolyzed erythrocytes at levels that are not sufficient to measurably increase total lung catalase activity.
Animals↗
Functional similarities of hepatic cystic and biliary epithelium: studies of fluid constituents and in vivo secretion in response to secretin.
Hepatic cysts are a frequent manifestation of autosomal dominant polycystic kidney disease, but little is known about their functional characteristics. The goals of our study were to define the composition of hepatic cyst fluid and to determine whether hepatic cysts secrete in response to intravenously administered secretin. We percutaneously punctured five hepatic cysts and one proximal renal cyst from six subjects with autosomal dominant polycystic kidney disease and one solitary hepatic cyst from a subject without autosomal dominant polycystic kidney disease. Most fluids had an electrolyte composition similar to serum. Fluid from all hepatic cysts had glutamyltranspeptidase concentrations above those found in serum [( cyst]/[serum] = 4.93 +/- 5.92), contained secretory component (the epithelial receptor for polymeric IgA) and had glucose concentrations less than 15 mg/dl. Fluid from both hepatic and renal cysts of subjects with autosomal dominant polycystic kidney disease, but not from the subject with the solitary hepatic cyst, demonstrated extensive changes in the electrophoretic mobility of several serum proteins. Initial intracystic pressures ranged from 16 to 40 cm H2O, were reduced 57% to 97% after aspiration of a portion of cyst fluid and were held constant during the secretion study. Within 8 min of the intravenous administration of secretin, secretion of fluid increased in two of three hepatic cysts and in the renal cyst. The electrolyte composition of cyst fluids was not altered by secretin. These data suggest that hepatic cystic epithelium has functional characteristics of biliary epithelium and that secretion by both hepatic and renal cysts may be hormonally regulated.
Aged↗
Effect of the time of administration of calcium acetate on phosphorus binding.
Phosphorus binders are given to patients with renal failure to increase gastrointestinal excretion of phosphorus. To determine the relative importance of the binding of dietary as compared with endogenous phosphorus and to determine the optimal dose schedule, we gave either 4.4 g of calcium acetate (25 mmol of calcium) or a placebo to six normal subjects on each of seven different schedules in a randomized sequence. The net gastrointestinal balance of phosphorus and calcium was determined by a one-day lavage technique. After a meal containing approximately 12 mmol of phosphorus, the mean phosphorus absorption (+/- SE) measured 9.17 +/- 0.36 mmol (78 percent) with placebo but decreased to 3.81 +/- 0.58 mmol (31 percent) when calcium acetate was given immediately before the meal (representing binding of 5.36 +/- 0.77 mmol of phosphorus). Similar binding was observed when calcium acetate was given immediately after the meal and when half the dose was given before and half after the meal. In contrast, when calcium acetate was given two hours after the meal or while the subject was fasting, phosphorus binding was reduced to 2.00 +/- 0.52 mmol and 1.81 +/- 0.84 mmol, respectively. Calcium absorption from calcium acetate averaged 21 +/- 1 percent when the binder was given with a meal; absorption from calcium acetate averaged 40 +/- 4 percent when the binder was given while the subject was fasting. We conclude that calcium acetate increases fecal excretion of phosphorus by binding both dietary and endogenous phosphorus, but the binding of dietary phosphorus is quantitatively much more important. For the most efficient phosphorus binding, calcium (and presumably other phosphorus-binding cations) should be given with meals.
Acetates↗
Cyclosporine therapy for psoriasis: serum creatinine measurements are an unreliable predictor of decreased renal function.
With increasingly widespread use of cyclosporine for the treatment of psoriasis, it is imperative to identify reliable markers of cyclosporine-induced nephrotoxicity. Five patients with extensive psoriasis and no significant preexisting renal disease were treated with oral cyclosporine (average dosage, 5 mg/kg per day; average duration of treatment, 9 weeks). Changes in serum creatinine measurements made immediately before and at the end of treatment were compared with changes in glomerular filtration rate as determined by 125I-iothalamate clearance. During treatment, the average serum creatinine value only increased from 1.0 +/- 0.2 to 1.1 +/- 0.3 mg/dl (+/- standard deviation), whereas iothalamate-based estimates of glomerular infiltration rate decreased from 100 +/- 22 to 63 +/- 37 ml/min/1.73 m2 (p less than 0.02). Simultaneous 125I-iothalamate and 24-hour creatinine clearances were obtained in two patients at the end of treatment and at 2 weeks after cyclosporine therapy. Glomerular filtration rates determined by iothalamate clearance were 14% to 30% lower than those calculated by 24-hour creatinine clearances. Neither serum creatinine measurements nor creatinine clearances (whether calculated or measured) accurately reflect the cyclosporine-induced decline in renal function as determined by glomerular filtration rate. In contrast, 125I-iothalamate clearance is a more accurate measurement of glomerular filtration rate, which provides a sensitive marker for monitoring potential cyclosporine-induced nephrotoxicity.
Adult↗
Calcium acetate, an effective phosphorus binder in patients with renal failure.
Calcium salts are increasingly used as phosphorus binders in patients with chronic renal failure. Calcium carbonate is the principal salt presently utilized, however, other calcium salts may be more effective and safer phosphorus binders. Theoretical calculations, in vitro experiments, and in vivo studies in normal subjects have shown calcium acetate to be a more effective phosphorus binder than other calcium salts. This salt has not previously been studied in patients with chronic renal failure. We used a one-meal gastrointestinal balance technique to measure phosphorus absorption, calcium absorption and phosphorus binding in six patients with chronic renal failure. Calcium acetate was compared with calcium carbonate and placebo. Equivalent doses (50 mEq Ca++) of calcium acetate bound more than twice as much phosphorus (106 +/- 23 mg) as calcium carbonate (43 +/- 39 mg) P less than 0.05. When phosphorus binding was factored for calcium absorption, calcium acetate bound 0.44 mEq HPO4 =/mEq absorbed Ca++ compared with 0.16 mEq HPO4 = bound/mEq Ca++ absorbed with calcium carbonate. More efficient phosphorus binding permits serum phosphorus concentration to be controlled with lower doses of calcium salts. The higher phosphorus binding/calcium absorption ratio coupled with a lower dose indicates that less calcium will be absorbed when calcium acetate is used for phosphorus control. Markedly positive calcium balance, hypercalcemia and ectopic calcification should be less likely to occur with this drug than other calcium salts.
Acetates↗
Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study.
Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ greater than H+ greater than Ca2+ greater than Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts.
Acetates↗
Rapid isolation of total RNA from mammalian tissues.
A rapid procedure for the isolation of total RNA from small amounts of mammalian tissue (35 to 150 mg) is described. Tissues were homogenized in the presence of RNase inhibitors but in the absence of strong detergents. Contaminants were removed by phenol/chloroform extraction and Sephadex column chromatography. Total RNAs were precipitated with ethanol and sodium acetate. The RNAs isolated were intact and suitable for mRNA quantitation via Northern blot or slot-blot analyses. This procedure isolates total RNAs in high yield and purity, without CsCl ultracentrifugation, and is especially useful when mRNAs must be quantitated from many samples.
Animals↗
Osmotic effects of polyethylene glycol.
Polyethylene glycol (PEG) has been used to increase the osmotic pressure of fluids used to cleanse the gastrointestinal tract. However, little is known about its osmotic activity. To investigate this activity systematically, solutions of PEG of differing molecular weights were made and subjected to measurement of osmolality by both freezing point depression and vapor pressure osmometry. Measured osmolality was increasingly greater than predicted from average molecular weight as PEG concentration increased. Measurement of sodium activity in NaCl/PEG solutions by means of an ion-selective electrode suggested that the higher than expected osmolality could be due in part to interactions that, in effect, sequestered water from the solution. Osmolality was consistently greater by freezing point osmometry than by vapor pressure osmometry. To determine which osmometry method reflected biologically relevant osmolality, normal subjects underwent steady-state total gut perfusion with an electrolyte solution containing 105 g/L of PEG 3350. This produced rectal effluent that was hypertonic by freezing point osmometry but isotonic by vapor pressure osmometry. Assuming that luminal fluid reaches osmotic equilibrium with plasma during total gut perfusion, this result suggests that the vapor pressure osmometer accurately reflects the biologically relevant osmolality of intestinal contents. We conclude that PEG exerts more of an osmotic effect than would be predicted from its molecular weight. This phenomenon may reflect interactions between PEG and water molecules that alter the physical chemistry of the solution and sequester water from the solution.
Freezing↗
Inhibition of colony-stimulating factor (CSF) production by postburn serum: negative feedback inhibition mediated by lactoferrin.
Fatal infections in severely burned patients are often preceded by a decline in the production of colony-stimulating factor (CSF) and the proliferation of granulocyte-macrophage stem cells (CFU-GM), and overwhelming sepsis is often associated with leukopenia. The underlying mechanisms accounting for these granulopoietic defects are poorly understood, but the fact that postburn serum has been shown to inhibit CSF production suggests that a humoral factor or factors may play a role. Previous work has demonstrated that plasma levels of lactoferrin (LF), a known inhibitor of CSF production, are elevated following burn injury. To determine if LF is responsible for serum-mediated inhibition of CSF production, serial plasma levels of LF were measured in 18 burn patients using an enzyme-linked immunoabsorbent assay (ELISA). LF was elevated within 24 hours of injury and was associated with an absolute granulocytosis which rapidly declined, reaching a nadir at postburn days 3 through 5. Postburn serum, especially when collected during the first 24 hours following burn injury, inhibited in vitro CSF production by normal human peripheral blood mononuclear cells. Pre-incubation of postburn serum with an LF antibody restored normal CSF production. These data suggest that LF may play an important role in the regulation of postburn granulopoiesis.
Adult↗