Critical care tomorrow: economics and challenges.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W L Thompson.
Explore the source record for details and available documents.
The validity of blood flow measurements made using radiolabeled microspheres (reference sample technique) has been well established in a variety of experimental models. Previous studies of the variability of the method emphasize tissue sphere number as the principle source of random variation. However, blood flow measurements depend on sphere distribution to both tissue and reference samples as well as on quantitation of different isotopes in a single tissue sample. In this study we examined the major determinants of relative error and variability in flow rate measurements inherent in the reference sample technique. Error magnitude was predicted from a statistical model, simulated with numerical analogs, and measured in anesthetized dogs with 15-micrometers microspheres. Theoretically, with 2,000 spheres in the reference sample and greater than or equal to 475 spheres in a tissue sample, blood flow can be measured with 10% accuracy at the 95% confidence level and with duplicate variability of 14%. Random errors in isotope quantitation were influenced by the specific activity of the isotope and the fractional distribution of a given isotope over the various energy windows. Suspension of tissue and reference sample spheres at different heights (0.2 cm) resulted in systematic flow errors of up to 13%. When errors due to separation of isotopes and differences in sample height were minimized, the major determinant of variability in flow measurements during simultaneous injection of differently labeled microspheres was the number of spheres in both tissue and reference samples.
Drugs can interfere with the normal intake, elimination, regulation and total body distribution of electrolytes. These drug-induced abnormalities may be dramatic and life threatening, posing diagnostic and management problems to the physician who is not familiar with them. Serum potassium concentrations can be altered as potassium shifts between the tissue and plasma compartments secondary to drug actions. In addition, drugs have been shown to interfere with the normal physiological functioning of the kidney with respect to potassium homeostasis, as well as the renin-aldosterone axis. The regulation of serum sodium levels is integrally related to the regulation of total body water. Thus, drugs that alter the regulation of antidiuretic hormone secretion and its action on the kidney can result in large changes in serum sodium concentrations. Abnormal losses or intake of sodium related to drug use can also have profound effects in the plasma compartment. The normally fine regulation of serum calcium concentrations can be easily upset by pharmacological therapy at the level of parathyroid hormone secretion and action, bone metabolism or renal calcium excretion. Through awareness of these drug-induced changes in electrolytes and the mechanisms involved, subtle and often dangerous problems in clinical management can be handled rationally.
Resting left ventricular wall motion abnormalities may represent myocardial scars or areas of viable muscle which are ischemic and may thus benefit from revascularization surgery. Improvement in wall motion in the 3-6 minute post-exercise recovery period as compared to the resting state was investigated as a possible criterion to predict myocardial viability in 168 patients with coronary artery disease. Of 125 patients with abnormal resting wall motion, 14 of 14 who improved regional function post-exercise also improved following coronary bypass surgery. However, wall motion improved postoperatively in an additional 55 patients who had not demonstrated post-exercise improvement. An increase in ejection fraction post-exercise occurred in patients with coronary disease as well as an additional group of 24 normal subjects. Thus in the post-exercise period, improvement in resting wall motion is a highly specific but insensitive predictor of myocardial viability.
The effects on absorption of drugs given by mouth of adsorbents (charcoals and resins) and cathartics (osmotic and oil) were studied in vitro and in vivo using acetaminophen (paracetamol) as a test drug. In vitro adsorption isotherms were measured at 37 degrees C in simulated gastric and gastric plus intestinal juices. Maximum binding capacity (MBC) of 16 charcoals and resins varied 30-fold, from 0.36 to 9.32 mol/kg. Dissociation constants varied directly with MBC. In vitro adsorption was little changed by addition of d-mannitol and d-sorbitol, N-acetylcysteine (NAC) or l-methionine. Acetaminophen (0.6 g/kg by orogastric tube) was given to 17 dogs protected by i.v. injections of NAC and methylene blue. One minute later, dogs were given: 1) water; 2) Norit A or Nuchar 1110 charcoal, 3 g/kg; 3) d-mannitol and d-sorbitol, 2 g/kg or castor oil, 3 ml/kg; or 4) both charcoal and either d-mannitol and d-sorbitol or castor oil. Cathartics alone decreased the area under plasma acetaminophen concentrations 15 to 30%. Charcoals alone reduced the area under plasma acetaminophen concentration 93%. Each cathartic diminished the charcoal inhibition of acetaminophen absorption. In mice given acetaminophen by orgastric tube, the acute lethality was decreased more by a new petroleum-based charcoal than by standard wood-based charcoals. Reduction of acetaminophen lethality in mice paralleled the in vitro MBC of adsorbents. Charcoals did not avidly adsorb l-methionine or NAC in vitro. Charcoal did not decrease the l-methionine or NAC protection of acetaminophen-poisoned mice. Charcoals with large MBC diminish absorption and lethality of acetaminophen taken by mouth; cathartics have little effect on acetaminophen absorption.
Ten nurses and 10 pharmacists or pharmacy technicians added hyperbaric potassium choride (KCl) 20 mEq to four types of iv fluid filled with "one liter" of dextrose, 5 g/dl, in water. Mean potassium concentrations in 240 containers filled under controlled conditions varied more than 12.4% from the mean concentration in 95% of bags and bottles. Mixing was quite incomplete, especially in flexible polyvinylchloride bags. In Viaflex bags that were not purposefully mixed, KCl concentrations during discharge varied from 71 +/- 21 (SEM) mEq/L at the beginning of fluid outflow to 11.8 +/- 3 mEq/L at the end. In a few containers, the maximum KCl concentration was 1000 times greater than the minimum. KCl mixing was improved slightly by storage of the container for 0.5 or 8 h and was greatly improved with vigorous purposeful mixing. There was little inhomogeneity of KCl in glass containers and in semirigid polyolefin containers. When KCl was added to the container during the course of fluid outflow, the maximal KCl concentrations in the discharge fluid were 21 times greater than the expected well-mixed KCl concentrations. Inhomogeneity of mixing of additives to parenteral fluids is another variable in control of drug effects in critical care and this should be minimized by forceful mixing after addition.
Rat liver was quantitatively subfractionated into free ribosomal, bound ribosomal, nuclear, and soluble fractions to determine the effects of infection and endotoxin treatment on hepatic RNA production and distribution. A 4-h pulse label of [14C]orotic acid was used to monitor newly transcribed RNA; distribution was determined by measuring RNA content at various times after infection or endotoxin treatment. A significant increase in the rate of RNA synthesis was seen by 12 h and continued through 20 h in response to Streptococcus pneumoniae infection. During the peak hours of the RNA response, redistribution of RNA into the bound ribosomal fraction takes place at the expense of the free ribosomes. However, in Salmonella typhimurium and its endotoxin, more involvement of the free ribosoma fraction during the early stages of the infection was apparent. These data suggest that the hepatic RNA response takes place in two stages, an early "endotoxin" response, resulting in redistribution of cytoplasmic RNA into free ribosomes, and a later "infection" response, involving the mobilization of the bound ribosomes.
HES products should be designated by both their number average of molecular weight (that determines colloidal activity) and molar substitution ratios. In addition to the original HES-70/70 developed in 1960, a rapidly excreted HES-50/50 has been available since 1977. HES-70/70 and human albumin are equivalent in both healthy and hypoalbuminemia subjects in regard to maximal and total effects on plasma volume, intravascular colloidal activity and plasma concentration of ingested colloid. Albumin and HES-70/70 are extravasated at nearly equal rates. Albumin elimination is predominantly monoexponential. HES-70/70 however, is partly metabolized and partly excreted in urine at rates that decrease progressively as the amount remaining in the body decreases. HES-50/50 has maximal effects on plasma volume and colloidal activity similar to those of dextran-40, but it is eliminated twice as rapidly and unlike dextran-40, does not accumulate on repeated ingestion of large doses. HES ingestion increases apparent serum activity of alpha amylase by slowing enzyme elimination. Anaphylactoid reactions have been infrequent and mild, even on repetitive ingestion in recurrent "Phoresis" donors. The effect of HES on coagulation in urine but does not slow urine flow by hyperviscosity. Hydroxyethylation of waxy starches yields safe colloids with the advantage of permitting selective control of drug effects by altering independently molecular size and rate of enzymatic hydrolysis, tailoring drug kinetics to specific uses.
In female mongrel dogs nephrotoxicity of three aminoglycosides (gentamicin, tobramycin and netilmicin) was compared with relation to the cortical aminoglycoside concentration. A standard regimen of 45 mg/kg/day with constant intravenous infusion and once daily dosing of each aminoglycoside was used, and in subsequent dogs netilmicin daily dose was increased to an average of 73 mg/kg/day.
Amphotericin B (2.5 mg/kg, administered intravenously) increased vascular resistance (renal more than pulmonary more than systemic) and decreased glomerular filtration and urine flow 94% in 16 anesthetized female mongrel dogs. Dopamine decreased renal vascular resistance 31% in 14 dogs; when amphotericin B was given with dopamine, there was partial antagonism of amphotericin B-induced renal vasoconstriction. Saralasin partially antagonized amphotericin B-induced renal vasoconstriction in seven dogs. When amphotericin B was given during combined infusion of dopamine and saralasin in eight dogs, renal blood flow remained at initial control levels, urine flow increased above initial levels, and glomerular filtration decreased only 21% from initial values. Amphotericin B increased renal vascular resistance 296% when given alone but only 41% in dogs during injection of both dopamine and saralasin (P = 0.002). The antagonism of amphotericin B-induced renal effects by the combination of dopamine and saralasin was significant and specific for the renal vascular bed.
Explore the source record for details and available documents.
This paper describes a rapid and simple procedure for the determination of benzodiazepines in biological samples. Five common benzodiazepines (diazepam, oxazepam, clorazepate, flurazepam, and chlordiazepoxide) and/or their major metabolites are extracted from a buffered serum sample at pH 9.2 by a mixture of toluene, hexane, and isoamyl alcohol. The phases are separated by centrifugation, and a small aliquot of the organic layer is injected into a gas chromatograph equipped with an electron-capture detector. The drugs are identified and quantitated by comparison with standards simultaneously processed similarly. A sample can be analyzed in about 30 min. The technique is illustrated by its application to sequential samples from a patient being treated for delirium tremens with large intravenous doses of diazepam. Serum diazepam, N-desmethyldiazepam, and oxazepam concentrations several times higher than usually encountered therapeutically were observed.
A whole-body computed tomography system for single-photon emitters was evaluated from the standpoint of spatial resolution, sensitivity, and thresholds for count densities with reference to standard doses of currently used radiopharmaceuticals in patients. In air and tissue equivalents, spatial resolution was relatively constant throughout the field of view and attentuation correction algorithms returned uniformity of response to within 10%. In a phantom of the human abdomen 1.5-cm spherical "cold" lesions and 1-cm "hot" lesions could be resolved. Aspects of the partial-volume effect were observed and investigated. To detect 1.5 cm-cold lesions in an abdominal phantom, five million events were required.
Hydroxyethyl starch is a derivative of amylopectin, the branched glycogen-like alpha-1,4-glucose polymer, the amylase hydrolysis of which is retarded by hydroxyethylation. If 70 to 90 per cent of the glucose polymer units contain hydroxyethyl groups, the intravascular persistence and urinary excretion of hydroxyethyl starch of a molecular weight of 435,000 is similar to that of Dextran 70. Hydroxyethyl starch and Dextran 70 are stored briefly in reticuloendothelial and hepatic cells, and cause swelling and vacuolation of renal tubules with little alteration of renal function. Elimination of hydroxyethyl starch from sites of tissue storage is much faster than elimination of the non-metabolized polymers acacia and polyvinylpyrrolidone. The distribution and excretion kinetics of hydroxyethyl starch are thus appropriate for a plasma substitute.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.