Delirium tremens.

BACKGROUND: The hyperadrenergic syndrome, delirium tremens, as contrasted with tile milder alcohol withdrawal syndromes, is a medical emergency. The clinical features of delirium tremens were carefully described almost 200 years ago. Since then, many therapies have been suggested as superior to preceding therapeutic approaches. Unfortunately, morbidity and mortality remain relatively unchanged for the last 100 years. METHODS: Using a literature review, we review the history of delirium tremens, including the suggested therapeutic approaches. RESULTS/CONCLUSIONS: We recommend a rational approach to management and therapy, based on present knowledge.

Office evaluation of pulmonary function: beyond the numbers.

Pulmonary function testing is useful in evaluating dyspnea, wheezing and cough, determining the severity of pulmonary disease, monitoring the response to therapy and assessing preoperative pulmonary risk. Accurate office spirometry requires routine preventive maintenance, cleaning and calibration of equipment and quality control measures. To obtain a flow-volume loop, the seated or standing patient is instructed to inspire maximally to total lung capacity, exhale as hard, fast and completely as possible (forced vital capacity [FVC]), and inhale quickly and deeply to total lung capacity (TLC). Spirometry reveals both obstructive and restrictive airway disease. Obstruction is characterized by reduced forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FEV1/FVC%), and normal to increased TLC and residual volume. Restriction is characterized by reduced TLC and residual volume and normal FEV1/FVC%. Spirometry may also reveal abnormalities of the upper airway, including the nasopharynx, vocal cords, trachea and proximal large airways.

Theophylline, fatigue, and diaphragm contractility: cellular levels of 45Ca and cAMP.

The relationship between variations in diaphragmatic contractility and corresponding changes in total tissue levels of 45Ca and adenosine 3',5'-cyclic monophosphate (cAMP) was examined. The contractile performance of perfused contracting rat diaphragms was manipulated with theophylline (10(-4) M), induced fatigue, or both. The increased contractility associated with theophylline was related to significant increases in 45Ca levels without changes in cAMP levels. Fatigue-diminished contractility was associated with increases in both 45Ca and cAMP levels. The increased 45Ca and cAMP levels associated with fatigue persisted, even in the presence of theophylline. Calcium channel blockade with 10(-4) M verapamil blocked the positive inotropic influence of theophylline as well as the theophylline-associated increase in 45Ca levels. Verapamil had no effect on either the fatigue-associated decreases in contractility or the fatigue-enhanced 45Ca uptake. The results of this study strongly suggest that the enhanced contractility associated with theophylline is related to its influence on cellular calcium metabolism. The elevated level of isotopic calcium measured in fatigued muscle probably represents calcium sequestered in the sarcoplasmic reticulum, the result of cAMP-enhanced Ca-adenosine triphosphatase activity.

Effect of glucocorticoids on the response of airway smooth muscle to catecholamine and resorcinol beta-agonists.

The influence of hydrocortisone (11 beta, 17 alpha, 21-trihydroxy-pregn-4-ene-3,20-dione) or of methylprednisolone (6 alpha-methyl-11 beta, 17 alpha-21-trihydroxy-1,4-pregnadiene-3,20-dione) on the response of airway smooth muscle to a variety of beta-adrenergic bronchodilators was evaluated using incubated guinea pig tracheal rings, preconstricted with histamine. The adrenergic agonists chosen for this study included the nonselective beta 1- and beta 2-catecholamine, isoproterenol, the selective beta 2-catecholamine, rimiterol, and the selective beta 2-resorcinols, fenoterol and terbutaline. When the incubated rings were pretreated with 10-50 micrograms/mL of the steroids, there was a significant enhancement in smooth muscle sensitivity and reactivity to rimiterol and isoproterenol. Tracheal response to fenoterol or terbutaline, on the other hand, was not altered by the glucocorticoids. When used alone, neither steroid exerted an inotropic influence on the tracheal smooth muscle. The results of our study indicate that glucocorticoid enhancement of adrenergic bronchodilators is selective for catecholamines, and not for resorcinols.

Diltiazem, verapamil, and nifedipine inhibit theophylline-enhanced diaphragmatic contractility.

The ability of theophylline to limit diaphragmatic fatigue and to improve contractility appears to be dependent upon alterations in calcium metabolism. The mechanism responsible for these actions, however, remains unclear. We used perfused, contracting, intact rat diaphragm to measure the influence of therapeutic theophylline levels (10(-4) M) on tension development, in the presence or absence of the three most commonly used calcium channel blocking agents, or in the absence of calcium. Concentrations of diltiazem (10(-4) M), verapamil (10(-5) M), or nifedipine (10(-6) M) sufficient to completely block transmembrane calcium channels, were used. During the experiment, each diaphragm preparation was subjected to one of two fatiguing procedures: one to mimic that encountered during tachypnea and one to mimic that encountered during increased respiratory resistance. Our findings showed that therapeutic levels of theophylline were related to statistically significant (p less than 0.0005) increases in diaphragmatic contractility under control conditions and to statistically significant reductions in the sensitivity of the preparation to fatigue. All three calcium channel blockers negated the positive influence of theophylline. Zero calcium also prevented theophylline from enhancing the contractile properties of the diaphragm. It is our conclusion that theophylline enhances the contractile properties of the diaphragm by altering the transmembrane movement of calcium. Calcium antagonists, in turn, inhibit the beneficial effects of theophylline on diaphragm function.

Sleep apnea, proteinuria, and nephrotic syndrome.

Renal abnormalities in patients with obstructive sleep apnea syndrome (OSAS) have not been previously described. Medical records of patients who had been evaluated for possible sleep apnea syndrome and had had complete polysomnograms and urinalyses were reviewed to determine the frequency of proteinuria. High-grade proteinuria (greater than or equal to 3+ on urinalysis) was found in 6 of the 34 patients with obstructive sleep apnea, but in none of 34 patients in a control group matched for sex, age, and weight. In three patients, proteinuria was in the nephrotic range (3.5 g/24 h). The weight (mean +/- SD) of the patients with obstructive sleep apnea (112.7 +/- 35.3 kg) was not significantly different from the control group (109.2 +/- 30.3 kg). Microscopic examination of renal tissue in one patient with OSAS showed minimal changes. In four patients who were followed for 3 years, proteinuria improved after therapy for sleep apnea syndrome. We suggest that proteinuria may not be uncommon in patients with severe obstructive sleep apnea syndrome and may be reversible with correction of the sleep apnea syndrome.

Studies of mediator involvement in cooling-induced alterations of guinea pig tracheal smooth muscle contractility.

Heat loss from airway smooth muscle is a potent stimulus which causes substantial, but poorly understood, alterations in muscle tension. This study considered the involvement of endogenous mediators in cooling-induced tension changes in incubated guinea pig trachea. Smooth muscle tension was monitored in tracheal cylinders which were carefully cooled from 37 to 30 degrees C in the presence or absence of various inotropic mediators. In our study, cooling alone, at a rate of 1 degree C/min, was associated with an average loss of smooth muscle tension of 88.2 mg. Cooling tracheal tissue that had been previously exposed to 3 X 10(-6) M histamine, however, caused an additional increase in tracheal tension of 133 mg, over and above that caused by histamine alone. In the presence of 10(-5) M prostaglandin F2 alpha, or 10(-5) M thromboxane B2, cooling was associated with respective losses of smooth muscle tension of 211.4 and 211.2 mg, as compared to the tension associated with these mediators when they were used alone under control conditions. When the speed of tracheal cooling was increased to 40 degrees C/min, there was a slight increase in tension for 20 sec followed by a pronounced and sustained relaxation. The mechanisms involved in the response of airway smooth muscle to cooling are complex. The results of our study, however, suggest that mediators may play a role in the cooling-induced alterations of airway smooth muscle tension.

Regional contractile responses in pulmonary artery to alpha- and beta-adrenoceptor agonists.

Contractile sensitivity and reactivity to alpha- and beta-adrenoceptor stimulation was studied in incubated rabbit pulmonary artery cylindrical segments of differing diameters. Distinct differences were noted between the responses of extra- and intra-pulmonary pulmonary arteries to norepinephrine and isoproterenol. The sensitivity to norepinephrine was largest in the intrapulmonary pulmonary arteries. Arterial reactivity to norepinephrine was greatest in the larger of the intrapulmonary vessel segments, diminishing considerably as the vessels became smaller. Cocaine did not cause substantial alterations in the response of any of the arterial segments to the alpha-agonist. Phentolamine, however, exerted its influence primarily in the smaller arterial segments. Vascular sensitivity to isoproterenol was least in the intrapulmonary pulmonary arteries. These smaller vessel segments, however, were more reactive to isoproterenol than were the extrapulmonary pulmonary arterial segments. Propranolol, at a concentration of 10(-8) M, was an effective antagonist of the beta-agonist; at a concentration of 10(-7) M, however, this antagonist was related to isoproterenol-induced arterial contraction, apparently by stimulation of alpha-receptor sites. The results of this study demonstrated a regional heterogeneity in the contractile response of the pulmonary artery to alpha- and beta-stimulation. The extrapulmonary arterial segments were found to be more sensitive to beta-stimulation than were the smaller, intrapulmonary, segments. The intrapulmonary arterial segments, on the other hand, were found to be more sensitive to alpha-stimulation than were the extrapulmonary segments.

Multiple mycetomas due to Pseudallescheria boydii.

A patient with pulmonary sarcoidosis had evaluation of hemoptysis. A CT scan of the chest showed bilateral upper lobe cavities and five separate mycetomas with air-crescent signs. Bronchial washings were positive on stains for fungal elements, and all cultures grew Pseudallescheria boydii. We have not seen a previous report of multiple fungus balls due to P boydii demonstrated by chest CT.

Therapeutic effect of posture in sleep apnea.

Four patients with mild to moderate obstructive sleep apnea were monitored first in the supine posture to establish a diagnosis of obstructive sleep apnea (apnea indices 33, 12, 22, 36). A second polysomnogram, obtained while the patients slept in the lateral posture, showed a dramatic decrease in apnea (apnea indices 5, 0, 0.2, and 0) and snoring. Each patient had an enlarged uvula, which moved to the side in the lateral posture. We conclude that sleeping in the lateral posture may be therapeutic in some patients with obstructive sleep apneas.

The influence of lanthanum on the subcellular distribution of calcium in the perfused dog heart.

A newly developed method was used to make a direct study of the influence of lanthanum on the subcellular distribution of isotopic and elemental calcium in the isolated perfused dog heart. The trivalent cation was introduced into the heart for the last 5 min of a 60 min perfusion period. Developed pressure and dP/dt were monitored continually from a fluid filled balloon positioned within the left ventricular chamber. At the end of the perfusion period, calcium was fixed within the myocardium by rapid freezing followed by vacuum desiccation at -60 degrees C. Enriched populations of sarcolemma and mitochondria were then obtained utilizing a newly developed nonpolar density gradient ultracentrifugation technique. Lanthanum was found to decrease dP/dt by 82.5% without significant changes in contractile rate. Atomic absorption spectrophotometric analysis revealed that lanthanum was associated with a 48.8% decrease in sarcolemmal calcium and a 159.6% increase in mitochondrial calcium. Lanthanum caused a 40.2% increase in the mitochondrial tissue/medium 45Ca ratio without significantly altering the isotropic activity of the sarcolemma. The results confirm that lanthanum-induced negative inotropy is associated with a displacement of sarcolemma-associated calcium. Surprisingly, the diminished contractility occurs with an increase in mitochondrial-associated calcium.

Initial roentgenographic manifestations of bacteriologically proven Mycobacterium tuberculosis. Typical or atypical?

Admission chest roentgenograms were reviewed of all patients diagnosed with pulmonary and extrapulmonary tuberculosis (TB) at the Medical College of Georgia--Eugene Talmadge Memorial Hospital (MCG-ETMH) during a five-year period from 1979 to 1983. Of 75 patients included, 51 had pulmonary TB, whereas 24 had extrapulmonary infection. Cavitary disease was common (28 of 51 patients with pulmonary TB). Forty-four of 51 patients with pulmonary TB had involvement of apical and/or posterior segments of the upper lobes with cavitation or infiltrates. Pleural effusion, parenchymal nodules, lymphadenopathy, and lower lung field disease were uncommon. Thirteen of 24 patients with extrapulmonary TB had abnormal admission chest roentgenograms, suggesting the possibility of Mycobacterium tuberculosis infection. Despite recent studies suggesting that TB presents with atypical roentgenographic features more commonly than reported in the past, the roentgenographic manifestations of TB in our series were typical of those previously described as pathognomonic for the disease.

Facilitation of isoproterenol induced airway smooth muscle relaxation by nifedipine.

The facilitating effect of nifedipine on isoproterenol induced airway smooth muscle relaxation was studied in guinea pig tracheas. For isometric force measurement, 4 mm tracheal cylinders were suspended in incubation chambers in oxygenated physiologic medium. After 90 minutes of equilibration under 2 grams resting tension, at a temperature of 37 degrees C and pH of 7.4, concentration response curves for isoproterenol were performed with and without the addition of a 1 X 10(-5)M nifedipine dose. The experiments were then repeated using tissues precontracted with histamine. Our data show that in the nifedipine pretreated tissues, the EC50 of isoproterenol is shifted to the left (p less than 0.05) probably due to further reduction in cytosolic calcium by nifedipine. Our findings suggest that nifedipine might have a role in the treatment of asthma and obstructive airway disease.

Temporal relationship of cyclic nucleotide levels and calcium exchange to histamine-induced tension development.

The purpose of these experiments was to study the temporal relationship between tension development in incubated guinea pig tracheal smooth muscle and changes in tissue levels of cAMP and cGMP, and isotopic Ca. Dose-response studies were performed with increasing concentrations of histamine both in the absence and presence of H1 receptor blockade using 10(-5) M diphenhydramine. The time course of tension development was subsequently determined in the presence of three concentrations of histamine shown to cause 50% (3 X 10(-6) M), 85% (9 X 10(-6) M), and 100% (5 X 10(-5) M) of maximal contraction. Tissue cyclic nucleotide and 45Ca levels were measured 20 sec, 1 min, and 6 min after the onset of contraction. For comparison, the influence of carbachol was also studied. Our findings demonstrate that there were no detectable alterations in tissue cAMP or cGMP levels during the initial phases of contractile change. In contrast, tissue isotopic Ca uptake increased early in histamine-induced contraction and was blocked by the H1 antagonist.

Expiratory flow limitation in large and small airways.

Obstructive airways diseases constitute 75% of all chronic respiratory diseases. This article briefly reviews the physlologic basis for flow limitation in large and small airways. Application of the physiologic principles described can lead to a better understanding of the normal mechanics of breathing and the various alterations resulting from diseases that limit airflow.

Crown ethers which influence cardiac and respiratory muscle contractility.

Guinea-pig tracheal smooth muscle and heart muscle demonstrated a variety of in vitro positive and negative inotropic responses to concentrations of crown ethers in the nmole/1 to mumole/1 range. It is suggested that these ionophoretic compounds have potential as therapeutic agents.