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Biomedical subjects

W L Thompson

Publications and source records attributed to W L Thompson.

At least 91 records · Page 5Linked to original sources

Management of alcohol withdrawal syndromes.

Withdrawal from alcohol (ethanol, ethyl alcohol) or other general sedatives leads to progressive hyperactivity that progresses from tremulousness, sleep disturbance, and hallucinosis, to the more serious rum fits and delirium tremens (DTs). Withdrawal can be prevented and, in most cases, arrested by prompt replacement of alcohol with paraldehyde, benzodiazepines or other general sedatives. Diazepam is appropriate replacement therapy for most patients. When delirium is manifest, the chance is greater than 15% that the patient will die, and this reaction cannot be aborted. The patient with DTs must be calmed with a general sedative that has a rapid onset of maximal effect to prevent overdosage. Diazepam, 5 mg intravenously every five minutes, permits evaluation of the maximal effect of each dose before the next dose is administered. Although some patients have advance sedative or alcohol withdrawal, great care must be taken to elicit the proper history of alcohol abuse so that sedative replacement therapy will prevent or abort early withdrawal, thus sparing the patient a mortality equivalent to that of acute myocardial infarction or Russian roulette.

Alcohol Drinking↗

Dopamine in the management of shock.

Shock is a syndrome with serious prognostic implications--the harbinger of death. Hypoperfusion of essential organs is common, though total blood flow may be significantly greater than normal. Specific therapy is directed to the specific inciting event--infection, abscess, tamponade, &c. Symptomatic therapy keeps the patient alive until we discover the specific problem or until he recovers spontaneously. The intravascular volume must be carefully monitored and corrected, using the pulmonary wedge pressure as the principal guide, and colloid osmotic pressure must be maintained. If the patient does not respond to volume augmentation alone then inotropic drugs may be needed, and of these dopamine is a selective vasodilator which redirects blood flow to the critical organs. The outstanding challenge in shock is the maldistribution of perfusion in the microvasculature. Although this may be ameliorated by the early administration of large doses of glucocorticoids, there is little convincing that these drugs constitute more than supportive therapy. Of greatest importance is reevaluation, reevaluation, and reevaluation. The patient in shock becomes a new patient every five minutes. Drugs that formerly worked, doses previously optimal--these are no guide because the situation changes so rapidly. The principles of management are to monitor vital functions, constantly vary drugs and doses, and continually attempt to put right all the parameters measured. This strategy will be more effective when we know what parameters to measure.

Blood Volume↗

Influence of the adrenal glucocorticoids on the stimulation of synthesis of hepatic ribonucleic acid and plasma acute-phase globulins by leucocytic endogenous mediator.

An injection of unpurified leucocytice endogenous mediator into rats results in an increased incorporation of [6(-14)C]orotate into hepatic RNA, an increase in the concentration of RNA associated with the bound ribosomal fraction of liver, and increases in the concentrations in serum of acute-phase proteins such as alpha2-macrofoetoprotein and haptoglobin. If given 3 days after adrenalectomy or 7 days after hypophysectomy,, leucocyte factor did not induce the increase in RNA synthesis or alpha2-macrofoetoprotein concentrations but did stimulate an increase in serum haptoglobin. When hypophysectomized or adrenalectomized rats received daily subcutaneous injections of 0.5mg of cortisol, leucocyte factor again induced a significant increase in the synthesis of hepatic RNA and an increase in the concentration of serum alpha2-macrofoetoprotein. These observations suggest that leucocyte factor can regulate acute-phase-protein synthesis at several different sites, one or more of which requires permissive action of the glucocorticoid hormones. Futher, leucocyte factor will stimulate an increase rate of incorporation of orotate into hepatic ribosomes when added in vitro in the presence of cortisol to a liver-perfusion system. Thus the stimulatory effect of leucocyte factor may be directy on liver but may require the presence of other hormones to stimulate the incorporation of orotate into RNA.

Animals↗

Hypocalcemia complicating acute leukemia.

Eighteen of 54 adults with acute leukemia developed severe hypocalcemia during a 20 month period. Hypocalcemia (mean lowest serum calcium 6.3 mg/100 ml with a range of 4.1 to 7.0 mg/100 ml) lasted 2-29 days and was symptomatic in all but one patient. Six patients were hypocalcemic at the time of death, 5 died within 1 week of hypocalcemia, and 2 had antibiotic-induced respiratory arrest. All patients had severe infections; 17 of 18 were with gram-negative organisms. No patient had severe azotemia, diarrhea, alkalosis, or hypoalbuminemia. Hypophosphatemia was seen in 14 patients, suggesting no hypoparathyroidism. The serum calcium of patients with acute leukemia should be measured frequently, especially when they have infection. Hypocalcemia is a sign of poor prognosis and should signal the need for careful observation of ventilation, caution in the use of aminoglycoside antibiotics, and vigorous attempts at calcium administration.

Adolescent↗

A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins.

A proteinaceous secretion from phagocytizing polymorphonuclear leukocytes, termed "leukocytic endogenous mediator" (LEM), has been shown to have marked effects on hepatic amino acid transport and RNA and protein synthesis. A single injection of LEM results in a marked accumulation of labeled nonmetabolizable model amino acids in the liver of normal rats. The LEM-stimulated uptake of amino acids by liver was observed in adrenalectomized, hypophysectomized, thyroidectomized, or diabetic rats and could not be duplicated by pharmacological doses of a large variety of hormones. In addition, LEM stimulated an increased uptake of alpha-aminoisobutyric acid by isolated livers during their perfusion in vitro. LEM also stimulated an increased incorporation of orotic acid into hepatic RNA of intact rats, especially into the bound ribosomal fraction. This increased synthesis of RNA preceded an enhanced hepatic production of a number of the acute-phase plasma globulins. LEM did not stimulate the adenylate cyclase-cAMP system in liver and was not found to utilize this system as a second messenger. Thus, the effects of LEM in stimulating hepatic amino acid transport appear to be direct, without mediation by other hormones, and to be independent of cAMP. On the other hand, the ability of LEM to stimulate RNA and acute phase globulin synthesis in liver may require the presence of physiological quantities of hormones such as adrenal corticoids.

Adenylyl Cyclases↗

Diazepam and paraldehyde for treatment of severe delirium tremens. A controlled trial.

Thirty-four patients with severe delirium tremens were allocated randomly to treatment with paraldehyde (10 ml rectally very 30 minutes) or diazepam (10 mg then 5 mg intravenously every 5 minutes) until they were calm but awake. Diazepam-treated patients became calm in one half the time needed to calm patients with paraldehyde. Half of the patients had delirium tremens in association with pneumonia, pancreatitis, or alcoholic hepatitis; these patients required twice as much paraldehyde or diazepam for initial calming as patients with delirium tremens alone. Maintenance of a calm state was accomplished easily with either diazepam, intramuscularly, or paraldehyde, rectally. Adverse reactions occurred in nine patients, all of whom had been treated with paraldehyde; these patients had greater degrees of fever, tachypnea, and tachycardia and required three times longer for initial calming than patients without adverse reactions. Diazepam given under this regimen is a safe and effective sedative for management of combative patients with severe delirium tremens.

Adult↗

Bone mineral content determined by functional imaging.

Quantitation of bone mineral by photon absorptiometry is a simple and accurate method for determining changes in bone volume and mineral content in serial studies. An extension of the scintillation camera method for studying such changes in the calcaneous is described. This technique is applicable to large areas of bone, thereby minimizing the effect of repositioning errors. Using a 40-mCi 241Am sheet source, a 2.1% reproducibility in bone phantoms and a 2.4% reproducibility in normal patients was achieved. Several case studies are presented to illustrate sensitivity and clinical application of the method. Although bone mineral determinations are now performed in a limited number of health care facilities, the scintillation camera method described in this report could increase the availability of these determinations significantly.

Adult↗

The clinical use of dopamine in the treatment of shock.

Dopamine is a direct-acting catecholamine with a short half-life that has many advantages in treating visceral hypoperfusion states such as shock and refractory heart failure. Unlike other inotropic drugs, dopamine directly dilates the mesenteric, renal, and cerebral vessels and redirects blood flow to essential viscera. This dopaminergic effect is prominent with doses of 100-700 mug/min in adults and is attenuated by phenothiazines and haloperidol. At doses of 700-1400 mug/min, dopamine also has a significant beta-adrenergic, inotropic effect, increasing myocardial contractility. The inotropic effect is equivalent to that of isoproterenol, epinephrine, and norepinephrine, but tachycardia, tachyarrhythmias, and angina may be less frequent with dopamine. In doses greater than 1400 mug/min, dopamine is a vasoconstrictor with pressor effects usually equivalent to that of norepinephrine. Dopamine dilates pupils, does not dilate bronchi, and does not shunt blood from viscera to skeletal muscles as does isoproterenol. Because dopamine increases myocardial contractility, selectively redistributes perfusion to essential viscera and allows a pharmacologic titration of effect, it is a logical first-choice catecholamine for treatment of shock and refractory heart failure.

Adrenergic alpha-Agonists↗

Rational use of albumin and plasma substitutes.

Salt-poor human albumin (25 g/dl) is a safe and effective colloid for increasing intravascular volume. It is usually given together with saline solutions at a final concentration of 5 g albumin per 100 ml infusion volume. Although relatively nontoxic, albumin costs about $120 per liter, more than ten times the cost of artificial macromolecular colloids used as "plasma substitutes". Hydroxyethyl starch (6 g/dl NaCl) is a new polysaccharide volemic colloid similar in effect to dextran-70; 70% of an infused volume remains intravascular at 3 hours and 30% at 24 hours. It is nonallergenic, causes no anaphylactoid reactions, and interferes with coagulation less than dextran-70 or dextran-40. Bleeding may be observed when doses of more than 1500 ml are given without blood replacement, especially in thrombocytopenic patients. The effects of dextran-70 and dextran-40 on inhibiting thrombogenesis and facilitating blood flow in small vessels are due largely to hemodilution; the relative efficacy of hydroxyethyl starch for these purposes has not yet been established. Hydroxyethyl starch is a safe and effective colloidal solution for replacement of lost blood and augmentation of blood volume.

Blood Viscosity↗

Effects of infection with Diplococcus pneumoniae on synthesis of ribonucleic acids in rat liver.

Rats infected with virulent Diplococcus pneumoniae developed a significant increase in the rate of incorporation of labelled orotate into hepatic RNA when compared with pair-fed controls inoculated with heat-killed organisms. The finding was readily detected in rats raised on either a low-protein diet (6% casein) or a diet containing adequate amounts of protein (18% casein). The increase in hepatic RNA synthesis was observed by 12h and was maximal by 16-20h after inoculation with the D. pneumoniae. Most of the infection-related increase in RNA synthesis was associated with the bound ribosomal RNA fraction of the liver. A small but less significant increase was observed in the synthesis of free ribosomal RNA. The increased synthesis of RNA in the liver of infected rats resulted in a marked elevation of the liver RNA/DNA ratio, the major increase being observed in concentration of bound ribosomal RNA fraction. When followed sequentially, the infection-related increase in synthesis of hepatic RNA was preceded by a flux of amino acids into liver and was followed by elevated synthesis rates of serum globulin proteins. These findings suggest that the infectious process was able to regulate hepatic RNA synthesis by altering the rate of transcription of new RNA. This mechanism was stimulated even in rats that had been severely depleted of body protein and amino acids by feeding them on a low-protein diet. The infection-related stimulation of liver RNA and protein synthesis thus appeared to take place at the expense of other body proteins.

Animals↗