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Biomedical subjects

L J Rubin

Publications and source records attributed to L J Rubin.

At least 127 records · Page 7Linked to original sources
PubMed1988

Effects of interleukin-2 on oxygen delivery and consumption in patients with advanced malignancy.

We evaluated the effects of fluid challenges on oxygen delivery (DO2) and oxygen consumption (VO2) in nine patients receiving immunotherapy with interleukin-2. Fluid resuscitation produced an increase in DO2 from 15.7 +/- 3.1 to 17.4 +/- 3.5 ml/min/kg (mean +/- SD, p less than 0.001), which was associated with a corresponding increase in VO2, from 2.8 +/- 0.7 to 3.1 +/- 0.6 ml/min/kg (p less than 0.01). These results suggest that oxygen consumption may be dependent on oxygen delivery in patients on IL-2 therapy. The presence of oxygen supply dependency may contribute to the multiple organ failure observed with IL-2 administration.

Adult↗
PubMed1987

Pulmonary vascular structural and functional changes in papain-induced emphysema in dogs.

We evaluated the pulmonary circulatory effects of emphysema produced by papain in 6 dogs that received 4 weekly treatments of papain administered by aerosolization. A control group of 6 dogs received saline treatments. Hemodynamic measurements were performed during normoxic and hypoxic (10% oxygen) ventilation approximately 3 and 6 months after treatment. Baseline hemodynamic parameters were comparable in both groups and were unchanged at 6 months in the control group. In the papain-treated group at 6 months, there were significant reductions in PaO2 (95 +/- 4 to 79 +/- 3 mm Hg, p less than 0.005) and increases in mean pulmonary artery pressure (12 +/- 1 to 18 +/- 3 mm Hg, p less than 0.05) and pulmonary vascular resistance (2.0 +/- 0.3 to 6.2 +/- 2.1 units, p less than 0.01). Morphometric evaluation demonstrated increased medial thickness in muscular pulmonary arteries less than 50 mu in size. Morphologic evaluation confirmed the presence of panlobular emphysema with papain administration. We conclude that chronic emphysema produced in dogs by aerosol administration of papain results in elevated pulmonary artery pressure, which is characterized pathologically by medial hypertrophy of small pulmonary arteries. This model appears suitable for further study of the pathogenesis of pulmonary vascular disease associated with chronic lung disease.

Animals↗
PubMed1987

Prostacyclin and PGE1 treatment of pulmonary hypertension.

Prostacyclin and PGE1 show promise in treatment of many forms of pulmonary hypertension. Their clinical use can be expected to increase as their pulmonary vasodilating effects become better known. There is as yet no unequivocal reason to choose one agent over the other, but several observations suggest that prostacyclin will eventually be preferred. First, prostacyclin appears to have a shorter half-life (1 to 2 min), which means that any drug-induced adverse effects will disappear more quickly. Although it is commonly said that up to 80% of PGE1 is metabolized with one passage through the lungs, in one study 34% of intravenously administered radiolabeled PGE1 remained in the bloodstream 20 min after administration. Second, prostacyclin causes less severe and less prolonged rebound platelet activation after discontinuation. Third, prostacyclin has been shown to reduce resting pulmonary vascular tone and hypoxic pulmonary vasoconstriction in virtually every published study in every species tested at every stage of development (fetal, newborn, and adult life); results with PGE1, although very impressive, have been less consistent. Nevertheless, there is little doubt that PGE1 is a powerful pulmonary vasodilator in most clinical situations complicated by pulmonary hypertension. Further, PGE1 is available for clinical use, while prostacyclin remains an investigational drug. Thus, it is likely that PGE1 will become the "nitroprusside" of the lesser circuit for intensive care use, a position PGE1 will hold alone at least until prostacyclin becomes available. Chronic infusions of prostacyclin may prove particularly useful in patients with primary pulmonary hypertension awaiting heart-lung transplantation. Eventually, orally available prostacyclin and PGE1 analogs will offer a new therapeutic avenue in many diseases complicated by chronic pulmonary hypertension.

Alprostadil↗
PubMed1987

Noninvasive evaluation of right ventricular function.

Numerous technologic advances have greatly facilitated the noninvasive analysis of right ventricular function. Nevertheless, important clues continue to be available to the astute clinician by physical examination. The chest x-ray is of rather limited utility. The electrocardiogram can show evidence of right atrial enlargement or right ventricular hypertrophy. Unfortunately, both sensitivity and specificity are deficient. Echocardiography is a widely available and potentially very accurate source of information concerning right ventricular dysfunction. Careful temporal analysis of the M-mode echocardiogram can give information beyond chamber size and wall thickness. Two-dimensional echocardiography allows more accurate determination of chamber size and wall thickness and also permits analysis of segmental wall motion and chamber contour. Doppler echocardiography allows measurement of pressure differences and flow kinetics. Preliminary data indicate that one can accurately assess pulmonary artery pressure and possibly right ventricular diastolic function. Color-flow mapping allows for accurate determination of valvular regurgitation and enhances the accuracy of standard Doppler echocardiographic techniques. Radionuclide analysis of the right ventricle by blood-pool imaging allows accurate determination of ejection fraction and wall motion. In addition, it may be possible to estimate pulmonary artery pressure. Use of short-acting radionuclides allows for serial imaging of the right ventricle after pharmacologic intervention or exercise. Perfusion scanning can show evidence of exercise-induced ischemia, although applicability to the right ventricle is somewhat limited. Avid scanning allows localizing of myocardial injury to the right ventricle. CT scanning of the heart is of limited clinical utility, because cardiac motion occurs too rapidly for accurate imaging. The advent of the cine-CT may overcome this problem and allow evaluation of right ventricular volumes and wall motion. Digital subtraction imaging allows for accurate video densitometric calculation of ejection fractions, but offers no advantage over other currently available techniques. Magnetic resonance imaging may prove to be the methodology of choice for analysis of right ventricular function, because it can give accurate measurement of right ventricular wall motion, ejection fraction, and (similar to Doppler flow studies) some indication of flow within the right-sided chambers. It will soon be possible to generate information concerning the biochemical content of the right ventricular myocardium, perhaps providing early evidence of hypertrophy or myopathy.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Output↗
PubMed1986

Cyclic nucleotide levels of the photosensitive irises of Bufo marinus and Lophius.

The sphincter pupillae muscle of several species contracts autonomously after light directly strikes the iris. The response is initiated by isomerization of rhodopsin in the sarcolemma. Light-induced release of CA2+ from internal stores is one step in the transduction process. The levels of cyclic AMP and cyclic GMP were measured after irises were stimulated by light. Stimulation by light does not produce measurable or consistent changes in the levels of either cyclic AMP or cyclic GMP within the photosensitive irises of at least two species, Bufo marinus and Lophius.

Animals↗
PubMed1986

Meat flavor volatiles: a review of the composition, techniques of analysis, and sensory evaluation.

Flavor is an important quality attribute which relates to the organoleptic characteristics of meat. Although perception of flavor is a complex phenomenon, odor is the most important single factor contributing to the overall characteristics of flavor. A large number of compounds have been identified in the volatile fraction of red meats and poultry. An overview of the chemical constituents present in the volatiles of beef, pork, mutton, and chicken is presented according to species and arranged by chemical class--hydrocarbons, alcohols, acids, aldehydes, ketones, sulfides, heterocyclic compounds, etc. The volatile components of cured and uncured pork are compared. The field of meat flavor is assessed in terms of what has been accomplished and the direction in which it may proceed. Techniques for analysis of these volatiles are briefly described.

Animals↗
PubMed1986

The effects of hydralazine on exercise capacity in pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Vasodilator therapy of pulmonary hypertension has been shown to improve hemodynamics in some patients, but the clinical benefits of this therapy have not been evaluated. We studied 14 patients who had pulmonary hypertension secondary to chronic obstructive pulmonary disease to determine the effect of hydralazine treatment on hemodynamics and maximal exercise. Baseline exercise in these subjects showed an abnormal pattern of excessive tachycardia and low stroke volumes, and the stroke volume correlated inversely with the pulmonary vascular resistance during exercise (r = -0.61, p less than 0.05). After 48 h of hydralazine there were decreases in the mean pulmonary artery pressure (43 +/- 8 to 38 +/- 8 mmHg, p less than 0.06) and pulmonary vascular resistance (3.97 +/- 0.97 to 2.88 +/- 1.28 units, p less than 0.05) measured at maximal exercise, and the maximal cardiac output was increased (8.05 +/- 2.57 to 10.13 +/- 2.79 L/min, p less than 0.05), but there was no change in symptom-limited maximal oxygen consumption (747 +/- 266 to 752 +/- 244 ml/min, p = NS). Significant increases in resting and maximal exercise values of minute ventilation and mixed venous oxygen tension were also noted with hydralazine. Repeat exercise testing after 2 to 4 months of chronic hydralazine therapy demonstrated no change in symptom-limited maximal oxygen consumption. We conclude that vasodilator therapy with hydralazine, although hemodynamically efficacious, does not increase exercise capacity in patients with severe chronic obstructive pulmonary disease and secondary pulmonary hypertension.

Exercise Test↗
PubMed1986

Long-term effects of nitrendipine on hemodynamics and oxygen transport in patients with cor pulmonale.

Recent studies have suggested that vasodilators may acutely improve pulmonary hemodynamics in patients with chronic obstructive pulmonary disease and cor pulmonale, but the effects of long-term therapy have not been assessed. We evaluated the hemodynamic and gas exchange effects of nitrendipine, a calcium channel blocker with a cardiovascular profile similar to nifedipine, acutely and after five days and six weeks of therapy in eight patients with stable COPD and cor pulmonale. After six weeks, nitrendipine significantly decreased both mean pulmonary artery pressure (40.4 +/- 10.3 to 31.2 +/- 6.6 mm Hg, p less than 0.01) and pulmonary vascular resistance (6.8 +/- 3.9 to 3.0 +/- 1.1 units, p less than 0.01), while cardiac index increased (2.4 +/- 0.8 to 3.6 +/- 1.0 L/min/m2, p less than 0.001). Despite a fall in arterial PO2 (53.1 +/- 18.7 to 45.5 +/- 11.3 mm Hg, p = NS), systemic oxygen transport increased by over 30 percent (843 +/- 284 to 1,111 +/- 373 ml/min, p less than 0.05). Systemic arterial pressure, pulmonary capillary wedge pressure, and heart rate were unchanged. Despite these hemodynamic changes, three patients died from complications of their underlying disease while receiving long-term therapy after eight, nine, and ten months. These preliminary findings suggest that long-term vasodilator therapy can result in persistent hemodynamic improvement in some patients with cor pulmonale secondary to COPD, although the impact of this form of therapy on survival remains to be clarified.

Aged↗
PubMed1986

Oxygen therapy titrated to raise mixed venous oxygen content in COPD.

Supplemental oxygen therapy delivered at concentrations which increase PaO2 greater than 60 mm Hg often has minimal effects on either pulmonary hemodynamics or the oxygen tension of mixed venous blood (PvO2). Since mixed venous hypoxemia has been shown to contribute to pulmonary vasoconstriction in experimental conditions and is a determinant of survival in chronic obstructive pulmonary disease (COPD), we evaluated the hemodynamic effects of oxygen therapy titrated to raise PvO2 in 12 COPD patients who underwent right heart catheterization. After room air measurements of mean pulmonary artery pressure, cardia output, and pulmonary vascular resistance, they were randomized to either supplemental oxygen therapy given to raise PaO2 greater than or equal to 60 mm Hg (group 1, n = 6) or to raise PvO2 greater than or equal to 36 mm Hg (group 2, n = 6). An oxygen-conserving nasal cannula and oxygen concentrator were used. Baseline PaO2, PvO2, and hemodynamics were identical in each group and hemodynamics after four hours and 48 hours of continuous oxygen therapy were unchanged. Ten patients were catheterized after four months of continuous oxygen therapy (group 1, n = 4; group 2, n = 6). Although PvO2 in group 2 had been raised to normal levels (39.2 +/- 1.2 mm Hg), there was no significant improvement in pulmonary hemodynamics. Our preliminary study suggests that oxygen titrated to raise PvO2 to the normal range has no greater hemodynamic effect than oxygen therapy as it is currently prescribed.

Aged↗
PubMed1986

Primary pulmonary hypertension. An analysis of 28 cases and a review of the literature.

The diverse potential etiologies and varying degrees of severity at the time of presentation suggest that primary pulmonary hypertension is a spectrum of disease states, all of which share the hemodynamic and pathologic correlates of pulmonary hypertension without a demonstrable cause. The course is variable, but manifestations of a low cardiac output or right ventricular failure imply a poor prognosis; the median survival is 2 to 3 years from the time of diagnosis. Although several systemic vasodilators have been demonstrated to improve pulmonary hemodynamics and ameliorate symptoms in some cases, these drugs may produce undesirable adverse effects, including death, in unresponsive patients. Additionally, the impact of vasodilator therapy on mortality from PPH has not been assessed. Combined heart-lung transplantation should be considered in patients who are unresponsive to vasodilators and who manifest the indicators of a poor prognosis.

Adolescent↗
PubMed1986

Therapy of secondary pulmonary hypertension.

Secondary pulmonary hypertension is seen in disorders that either interfere with gas exchange within the lung or in which large portions of the pulmonary vasculature are obliterated. Because the causes are diverse, there is no uniform approach to therapy. The approach to treatment should be methodic, but aggressive and primarily directed at improving the underlying disease process. Other forms of therapy, which are more controversial, should be reserved for patients with refractory cor pulmonale and should be instituted cautiously and their effects monitored closely.

Bloodletting↗
PubMed1985

Isolation and characterization of the inositol cyclic phosphate products of polyphosphoinositide cleavage by phospholipase C. Physiological effects in permeabilized platelets and Limulus photoreceptor cells.

Cleavage of the polyphosphoinositides, catalyzed by phospholipase C purified from ram seminal vesicles, produces phosphorylated inositols containing cyclic phosphate esters (Wilson, D. B., Bross, T. E., Sherman, W. R., Berger, R. A., and Majerus, P. W. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 4013-4017). In the present study we describe the isolation and characterization of inositol 1:2-cyclic 4-bisphosphate and inositol 1:2-cyclic 4,5-trisphosphate, the two cyclic phosphate products of phospholipase C catalyzed cleavage of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, respectively. We established the structures of these two cyclic compounds through 18O labeling of phosphate moieties, phosphomonoesterase digestion, and fast atom bombardment-mass spectrometry. We examined the physiological effects of these compounds in two systems: saponin-permeabilized platelets loaded with 45Ca2+ and intact Limulus photoreceptors. Both inositol 1:2-cyclic 4,5-trisphosphate and the noncyclic inositol 1,4,5-trisphosphate, but not inositol 1:2-cyclic 4-bisphosphate, release 45Ca2+ from permeabilized platelets in a concentration-dependent manner. Injection of inositol 1:2-cyclic 4,5-trisphosphate into Limulus ventral photoreceptor cells induces both a change in membrane conductance and a transient increase in intracellular calcium ion concentration similar to those induced by light. We injected inositol 1,4,5-trisphosphate and inositol 1:2-cyclic 4,5-trisphosphate into the same photoreceptor cell and found that the cyclic compound is approximately five times more potent than the noncyclic compound in stimulating a conductance change. We speculate that inositol 1:2-cyclic 4,5-trisphosphate may function as a second messenger in stimulated cells.

Animals↗
PubMed1985

A comparison of the acute hemodynamic effects of prostacyclin and hydralazine in primary pulmonary hypertension.

In patients with primary pulmonary hypertension the administration of a vasodilating drug is often used to test pulmonary vasoreactivity. Hydralazine has been employed as a test drug, but because of its long duration of action there is a risk of sustained systemic arterial hypotension in patients with a fixed pulmonary vascular resistance. In this study we compared the acute hemodynamic effects of intravenous prostacyclin, a potent, short-acting vasodilator, with the effects of oral or intravenous hydralazine. Both prostacyclin and hydralazine increased cardiac output and decreased systemic pressure without changing pulmonary arterial pressure in seven patients with primary pulmonary hypertension. The average decrease in total pulmonary resistance with prostacyclin (-46% +/- 5%) was more than that with hydralazine (-32% +/- 6%). The respective decreases in total systemic resistance were -50% +/- 4% vs -43% +/- 6%. The percent changes in individual responses to the two agents were correlated (p less than 0.05) for pulmonary arterial pressure, systemic arterial pressure, total pulmonary resistance, and total systemic resistance. We concluded that the pulmonary hemodynamic effects of prostacyclin resembled those of hydralazine. Prostacyclin may predict the acute pulmonary hemodynamic effects of hydralazine in primary pulmonary hypertension and because of its prompt, brief action may provide greater patient safety.

Blood Pressure↗
PubMed1985

Nafazatrom (Bay g 6575) blunts canine hypoxic pulmonary vasoconstriction: evidence for a prostaglandin-mediated mechanism.

The eicosanoids are circulating vasoactive substances which may serve as modulators of pulmonary vasomotor tone. Nafazatrom (Bay g 6575) has been reported to raise circulating levels of prostaglandin I2 (PGI2) either by stimulating its synthesis or inhibiting its metabolism, and may also decrease leukotriene synthesis by inhibiting lipoxygenase. We evaluated the hemodynamic effects of nafazatrom administered intravenously in doses of 2,5, and 10 mg/kg in intact, anesthetized dogs ventilated with 21% and 10% oxygen. The hypoxia-induced increase in pulmonary vascular resistance was blunted by nafazatrom in an inverse dose-dependent fashion. Pretreatment with the cyclooxygenase inhibitor indomethacin (5 mg/kg subcutaneously twice daily for two days) abolished the response to low-dose nafazatrom. The pulmonary vasodilator response to the infusion of arachidonic acid (100 micrograms/kg/min) during hypoxic ventilation was blocked by the 10 mg/kg dose of nafazatrom. We conclude that nafazatrom blunts hypoxic pulmonary vasoconstriction in a manner consistent with a drug-induced increase in PGI2 activity, and that the inverse dose-dependent effects of the drug which we observed are due to an inhibition of cyclooxygenase at higher doses.

Animals↗
PubMed1985

Pulmonary thromboembolic disease--diagnosis, management and prevention.

Pulmonary embolism remains a serious condition which has generated controversy regarding both the optimal diagnostic and therapeutic approaches. The development of newer modalities will eventually yield more efficient and safe approaches to both diagnosis and therapy; however, at the present time there is no definitive approach that can be recommended, and management must be individualized based on the patient's clinical status and the experience and expertise available at a particular institution.

Anticoagulants↗
PubMed1985

The effects of eicosanoid synthesis inhibitors on normoxic and hypoxic pulmonary vascular tone in dogs.

Prostaglandins have been implicated as possible modulators of normoxic and hypoxic pulmonary tone partly because of studies using cyclooxygenase inhibitors, but these drugs may exert effects that are independent of prostaglandin cyclooxygenase. We evaluated the hemodynamic effects of the acute intravenous administration of 3 cyclooxygenase inhibitor drugs in doses that inhibit prostaglandin synthesis in intact anesthetized dogs: indomethacin 5 mg/kg, meclofenamate 5 mg/kg, and ibuprofen 12.5 mg/kg. During room air ventilation, the administration of indomethacin produced an increase in mean pulmonary arterial pressure (8.0 +/- 1.27 to 13.1 +/- 1.52 mmHg, p less than 0.01) and pulmonary vascular resistance (1.2 +/- 0.23 to 2.7 +/- 0.39, p less than 0.01), whereas meclofenamate and ibuprofen had no effect. Indomethacin given during hypoxic ventilation slightly but insignificantly increased pulmonary artery pressure and pulmonary vascular resistance when compared with hypoxia alone and with the administration of vehicle or meclofenamate. Treatment with indomethacin methacin or meclofenamate 5 mg/kg given subcutaneously twice daily for 2 days had no effect on normoxic or hypoxic pulmonary tone. The combined cyclooxygenase-lipoxygenase inhibitor BW 755C in doses of 25 mg/kg given intravenously did not inhibit hypoxic pulmonary vasoconstriction. We conclude that prostaglandins do not appear to play a major physiologic role in modulating normoxic or hypoxic pulmonary vasomotor tone in intact anesthetized dogs, and that the indomethacin-induced increases in pressure and resistance are independent of inhibition of prostaglandin cyclooxygenase.

Animals↗
PubMed1985

Calcium channel blockers in primary pulmonary hypertension.

The demonstration that the calcium channel blockers reduce pulmonary vasomotor tone in experimental models of pulmonary hypertension has served as the rationale for their use in the management of primary pulmonary hypertension. The three currently available agents, verapamil, nifedipine, and diltiazem, have varying degrees of pulmonary vasoactivity. Experience with their use is reviewed.

Calcium Channel Blockers↗